Exosomes: Current use and future applications.
Exosomes are endosomal-derived vesicles that play a critical role in cell-to-cell communication and are secreted in several biological fluids including serum, saliva, urine, ascites, and cerebro-spinal fluid amongst others. Exosomes are small (30-150 nm diameter) with a distinctive bilipid protein structure. They can carry and exchange various cargos between cells and are used as a non-invasive biomarker for several diseases. Exosomes are considered the best biomarkers for cancer diagnosis, owing to their unique characteristics. Here, we provide a review of the up-to-date applications of exosomes, derived from various sources, in the prognosis and diagnosis of several diseases including cancer, cardiovascular and regenerative diseases as well as, arthritis, neurological diseases, and diabetes mellitus. The role of exosomes and their applications in biomedical research and preclinical trials have also been briefly discussed.


[123I]Mtr-TOCA, a radioiodinated and carbohydrated analogue of octreotide: scintigraphic comparison with [111In]octreotide.
Scintigraphy with maltotriose-[123I]Tyr3-octreotate ([123I]Mtr-TOCA) is compared with [111In]DTPA-Phe1-octreotide ([111In]OC) to assess the differences in pharmacokinetics and imaging properties as well as to estimate the therapeutic potential of the corresponding [131I]Mtr-TOCA. Six patients with somatostatin receptor (sstr)-positive tumours were assessed using a dual-head gamma camera. After injection of 137 +/- 28 MBq [123I]Mtr-TOCA, dynamic data acquisition of the upper abdomen (30 min) was performed followed by whole-body scans at 0.5 h, 1 h, 3 h and 20 h as well as by SPECT imaging (tumour) at 2 h. [111In]OC scintigraphy was performed by acquiring whole-body scans (4 h, 24 h) and SPECT (24 h). Using a region of interest (ROI) method, tissue and tumour bound activity was assessed and dosimetry performed. [123I]Mtr-TOCA shows rapid tumour uptake. Up to 4 h, tumour/organ (tu/org) ratios are stable and generally higher than with [111In]OC. From 3 h to 20 h, tu/org ratios increase for spleen, remain stable for liver and decrease significantly for all other tissues. In contrast, with [111In]OC, tu/org ratios decrease slightly between 4 h and 24 h for liver, spleen and kidney and increase for all other tissues. On [123I]Mtr-TOCA scintigraphy, a total of 27 lesions are detected, whereas 33 lesions are detected on [111In]OC scintigraphy (p=0.50). Effective patient absorbed dose is 1.9 +/- 0.9 mSv per 100 MBq [123I]Mtr-TOCA. Compared with [111In]OC, [123I]Mtr-TOCA enables faster imaging of sstr-positive tumours with a lower radiation burden to the patient. [123I]Mtr-TOCA and [111In]OC allow for tumour imaging with almost identical contrast and diagnostic yield. As regards peptide receptor radionuclide therapy, radioiodinated Mtr-TOCA is hampered by limited intratumoural activity retention


In vivo human MCP-1 transfection in porcine arteries by intravascular electroporation.
The purpose of this study was to develop a nonviral gene transfer method for therapeutic delivery of the human monocyte chemoattractant protein-1 (MCP-1) in patients with peripheral artery disease, using local catheter-mediated electrotransfer of naked plasmid DNA into arteries. Arterial walls of the A. profunda femoris of pigs were transfected either with a human MCP-1 or with a firefly luciferase-encoding DNA construct. The efficacy of electrotransfer of DNA was analyzed after 2 days by quantitative polymerase chain reaction (PCR) or luciferase activity measurements. To optimize MCP-1 gene transfer conditions, a voltage range of 60-150 V was applied as a train of six square pulses of 20 ms each at 1 Hz and was combined with a dose of 150 microg DNA. Subsequently, the optimized voltage was used to test a dose range of 80-300 microg DNA. The voltage optimum for arterial transfection was observed at 80 volts. Using this setting, the dose application of 300 microg MCP-1 plasmid DNA (the maximal dose tested) demonstrated the highest MCP-1 expression signal. The electric pulses and the transfer and expression of human MCP-1 per se did not induce endogenous porcine MCP-1 expression in treated arteries. Interestingly, angioplastic predilation of the artery before gene transfer, which had originally been postulated to enhance transfection by improving access of the plasmid to subendothelial cell layers, resulted in an attenuated transfection efficacy. The present study demonstrates that transluminal catheter-based electroporation provides an efficient technology for nonviral intravascular gene transfer by just applying unformulated DNA.


Assessment of Heavy Metal Contamination and the Probabilistic Risk via Salad Vegetable Consumption in Tabriz, Iran.
Considering the importance of vegetables as a source of micronutrients and fibers in a balanced diet, there is still a concern that vegetables could also be a source of toxic heavy metal contaminants. The study aimed to determine the concentrations of lead (Pb), cadmium (Cd), arsenic (As), chromium (Cr), copper (Cu), nickel (Ni), and zinc (Zn) in the salad vegetables sold in Tabriz city, Iran, and to evaluate the probabilistic health risk assessment. The amount of toxic metals in 240 samples was evaluated by atomic absorption spectrophotometer (AAS) method. The average levels of toxic metals in the samples were found to be 1.59, 1.26, 1.42, 4.89, 13.38, 1.01, and 32.65 mg/kg for Pb, Cd, As, Cr, Cu, Ni, and Zn, respectively. According to the results, Zn and Cu had the highest concentration, whereas the lowest concentration belonged to Ni. The rank order of the toxic elements in the samples based on target hazard quotient (THQ) values was Cr > Cd > As > Pb > Cu> Zn > Ni, for both females and males. Leafy vegetables had a higher amount of total target hazard quotient (TTHQ) than tuber crops for both males and females. The carcinogenic risks of As and Pb were 0.032 and 0.03 in the females and 0.22 and 0.19 in males. According to the finding, there may be a potential risk of toxic metals, especially Cr, Cd, and As, for both females and males in Tabriz through the consumption of vegetables.


The impact of the fecal stream and stasis on immunologic reactions in ileal pouch after restorative proctocolectomy for ulcerative colitis: a prospective, pilot study.
The etiology of pouch inflammation after restorative proctocolectomy is unknown. The fecal stream and immunological reactions are potential pathological factors. This study was performed to examine the impact of the fecal stream and stasis on immunological reactions in the pouch. Patients who underwent a restorative proctocolectomy with a covering ileostomy for ulcerative colitis were studied. Mucosal biopsy specimens were obtained from both the pouch and the proximal ileum at the time of ileostomy closure, and 3, 6, and 12 months after ileostomy closure. As a control group, normal ileal biopsies were obtained from patients with colonic polyps. At the time of ileostomy closure, mucosal interleukin-1beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha levels in the pouch and the proximal ileum were not significantly different from those in the normal control group. At 3 months after ileostomy closure, the mucosal cytokine levels in the pouch increased significantly compared with those at ileostomy closure, and their levels were significantly higher than those in the proximal ileum. At 6 and 12 months after ileostomy closure, the mucosal cytokine levels in the pouch did not change significantly compared with those at 3 months after ileostomy closure. The mucosal cytokine levels in the proximal ileum did not change significantly during the entire study. The immunological reactions in the pouch occurred soon after ileostomy closure, and continued for at least 1 yr. The fecal stream and stasis play an important part in the pathogenesis of immunological reactions in the ileal pouch.


CheXPrune: sparse chest X-ray report generation model using multi-attention and one-shot global pruning.
Automatic radiological report generation (ARRG) smoothens the clinical workflow by speeding the report generation task. Recently, various deep neural networks (DNNs) have been used for report generation and have achieved promising results. Despite the impressive results, their deployment remains challenging because of their size and complexity. Researchers have proposed several pruning methods to reduce the size of DNNs. Inspired by the one-shot weight pruning methods, we present CheXPrune, a multi-attention based sparse radiology report generation method. It uses encoder-decoder based architecture equipped with a visual and semantic attention mechanism. The model is 70% pruned during the training to achieve 3.33× compression without sacrificing its accuracy. The empirical results evaluated on the OpenI dataset using BLEU, ROUGE, and CIDEr metrics confirm the accuracy of the sparse model viz-a`-viz the dense model.


Determining the Impact of Lifestyle on the Health of Primary School Children in Slovenia Through Mixed Membership Focus Groups.
Lifestyle choices made by children and adolescents can lead to a variety of health problems. It is therefore crucial to evaluate the state health-related lifestyles of primary school children's and identify areas for improvement. The aim of this study was to investigate the experiences and perspectives of those involved in educating current generations of primary school children about their lifestyle and the associated health implications of their behavior. Four focus groups were formed, comprising parents, primary school teachers, health professionals, and leisure activity teachers, with five participants in each group. Semi-structured interviews were conducted with each group as part of the qualitative research paradigm of the study. The study revealed three central themes, emphasizing the need to promote health and educate children about healthy behaviors, environmental influences, and health literacy. Community nurses need to take a proactive role in promoting school health. Although adults, peers, and the environment exert a strong influence on children's lifestyles, they often fail to live up to their responsibilities and allow harmful habits to form. To instill positive behaviors and an optimistic attitude towards a healthy lifestyle, all those involved in a child's education need to collaborate. Health-related topics should be included or reinforced in primary school curricula, and parents and school staff should receive appropriate training.


Potential benefit of lamotrigine in managing ketamine use disorder.
Ketamine is an anesthetic derivative of phencyclidine (PCP; 'Angel dust') with dissociative, analgesic and psychedelic properties. Ketamine has become a popular recreational drug of abuse in many parts of the world in recent years. The preclinical studies demonstrate the reinforcing effects of ketamine and long-term ketamine abuse induces a delayed and persistent upregulation of dopamine system. In humans, there have been concerns about its liability to development of addiction. The dilemma of mental professionals in managing the treatment-seeking ketamine abusers comes from a lack of effective pharmacotherapy. Limiting evidence showed that lamotrigine, which inhibits glutamate release, is effective to reduce cocaine craving. We propose that lamotrigine might be beneficial for managing ketamine use disorder clinically. We also reported one case of ketamine use disorder who experienced a great reduction in craving and ketamine use after taking lamotrigine. Although the mechanisms underlying neuroadaptation and reward related to ketamine are not entirely clear, future clinical trials are needed to advance our understanding of the benefit yielded by lamotrigine to treat ketamine use disorder.


5,6-Methylenedioxy-2-aminoindane: from laboratory curiosity to 'legal high'.
The fully synthetic 'legal high' 5,6-methylenedioxy-2-aminoindane (MDAI) is an analogue of 3,4-methylenedioxymethamphetamine. Although developed in the 1990s, it was not widely abused until 2010. However, mephedrone was banned in the UK in April 2010, and almost immediately, MDAI was widely advertised as a legal alternative. This paper provides both an overview of the current state of knowledge of MDAI and a critical analysis of online available information relating to its psychoactive effects, adverse reactions and use in combination with other drugs. The literature on MDAI was searched in three databases: PsycInfo, PubMed and MedScape. Once the availability of information on MDAI was identified within these websites, further specific searches were carried out for narratives focusing on the nature of its effects on users, motivations behind its recreational use and possible trends of misuse, and any other relevant information. Internet-sourced products have been shown variously to contain mephedrone, and mixed compositions of inorganic substances, while containing no MDAI. Numbers of Internet searches have been considerably higher in the UK compared with Germany and the US. Better international collaboration levels may be needed to tackle the novel and fast growing phenomenon of novel psychoactive drug availability from the web.


Enhancing enzymatic digestibility of bamboo residues using a three-constituent deep eutectic solvent pretreatment.
A three-constituent deep eutectic solvent (3c-DES) pretreatment with choline chloride-oxalic acid-ethylene glycol was applied to examine its effectiveness on bamboo residues. The 3c-DES pretreatment can remove 91.09% xylan and significantly improved the 72 h hydrolysis yield of D. sinicus by 6.3 and 1.7 times as compared with the liquid hot water and two-constituent deep eutectic solvent (2c-DES) pretreatment. The introduction of ethylene glycol (EG) into choline chloride (ChCl)/ oxalic acid (OA) decreased the content of surface lignin and the condensation of lignin, which contributed to the increase of hydrophilic nature and cellulose accessibility in substrates. Moreover, higher glucose (85.72%) and xylose (91.05%) yields of 3c-DES pretreated bamboo were achieved with the addition of Tween 80. The 3c-DES system provides an alternative approach for the development of efficient bamboo pretreatment, and had broad space for bamboo biorefinery in southern China.


Cost-effectiveness of gastrostomy placement for children with neurodevelopmental disability.
Malnutrition and growth deficiency are common in neurologically impaired children. Gastrostomy placement has been shown to result in significant catch-up growth, improved health of the child and reduction in family stress; its cost-effectiveness has not been investigated. Costs related to gastrostomy placement are estimated here from a prospective controlled study of children referred to a tertiary paediatric centre in the UK. Costs of inpatient stay, medication, tests, general practitioner consultations, community healthcare, equipment, and parents' indirect costs were estimated at baseline and follow-up. Costs of the different types of gastrostomy surgery are given. Results for both time periods were available for 54 of the 76 children recruited to the study. Five-day food diaries were kept at baseline and follow-up. Costs of food increased slightly but not significantly post surgery from pound sterling 33 to pound sterling 40 (Euro 44 to Euro 54, US$65 to US$78) per week. Variation in cost between cases was considerable but the mean net cost difference of pound sterling 20.80 (CI - pound sterling 43.79 to pound sterling 85.35) (Euro 28 (CI Euro-59 to Euro 115), US$41 (CI US$-86 to US$167)) per week per child including for food and surgery, was also not significant. Community service costs were significantly lower post surgery. Few parents reported personal costs at either time point, although many had reduced or stopped paid work to care for the child. As gastrostomy placement for these children resulted in significant clinical benefit at no significant extra cost, it is concluded that the procedure is cost-effective.


Review on arsenic environment behaviors in aqueous solution and soil.
Arsenic pollution in environment has always been an important environmental problem that has attracted wide attention in recent years. Adsorption is one of the main methods of treatment for arsenic in the aqueous solution and soil because of the advantages of high efficiency, low cost and wide application. Firstly, this report summarizes the commonly and widely used adsorbent materials such as metal-organic frameworks, layered bimetallic hydroxides, chitosan, biochar and their derivatives. The adsorption effects and mechanisms of these materials are further discussed, and the application prospects of these adsorbents are considered. Meanwhile, the gaps and deficiencies in the study of adsorption mechanism was pointed out. Then, this study comprehensively evaluated the effects of various factors on arsenic transport, including (i) the effects of pH and redox potential on the existing form of As; (ii) complexation mechanism of dissolved organic matter and As; (iii) factors affecting the plant enrichment of As. Finally, the latest scientific researches on microbial remediation of arsenic and the mechanisms were summarized. The review finally enlightens the subsequent development of more efficient and practical adsorption material.


Correlation between ferromagnetic and isotopic tracers for sentinel lymph node detection in cutaneous melanoma: IMINEM study.
The usefulness of sentinel lymph node biopsy (SLNB) in staging cutaneous melanoma has been proven. Therefore, different tracers have been used to identify the sentinel lymph nodes (SLNs). The use of isotopic tracers together with radioactivity detectors allowed a much more precise and direct approach to the SLNs. However, not all centres have access to a Nuclear Medicine department hindering sentinel lymph node detection (SLND) and consequently, other markers such as ferromagnetic tracers have been evaluated looking for the same advantages and effectiveness as isotopic tracers. Ferromagnetic tracers have proven their usefulness in other cancer entities such as breast, prostate and thyroid cancer. The objective was to assess the detection and concordance rates between isotopic and ferromagnetic techniques for SLNB in cutaneous melanoma. Isotopic SLNB technique and ferromagnetic tracer were compared for cutaneous melanoma in a non-inferiority multicentre prospective study carried out in six Spanish hospitals. A total of 60 patients were recruited and 133 lymph nodes removed. The detection rate was slightly higher with ferromagnetic tracer in head-neck and trunk melanomas, and with isotopic tracer in limbs. The patients' and nodes' concordance rates between both techniques for ex vivo samples were 95% and 86% for head-neck and trunk tumours and 97% and 93% for limbs tumours, respectively. The concordance rates for involved nodes were 100% and 88.2% for patients and nodes, respectively. The intraoperative detection and biopsy of SLN in cutaneous melanoma using a ferromagnetic was a reliable alternative method to the isotopic technique in cutaneous melanomas.


The interrelationship between sleep, diet, and glucose metabolism.
Obesity and type 2 diabetes (T2D) are increasingly common worldwide. While these disorders have increased in prevalence over the past several decades, there has been a concomitant reduction in sleep duration. Short sleep duration has been associated with higher rates of obesity and T2D, and the causality of these associations and their directionality, continue to necessitate evaluation. In this review we consider the evidence that sleep is an intrinsic factor in the development of obesity and chronic metabolic disorders, such as insulin resistance and T2D, while evaluating a potential bi-directional association. We consider the evidence that diet and meal composition, which are known to impact glycemic control, may have both chronic and acute impact upon sleep. Moreover, we consider that postprandial nocturnal metabolism and peripheral glycemia may affect sleep quality. We propose putative mechanisms whereby acute effects of nighttime glucose excursions may lead to increased sleep fragmentation. We conclude that dietary manipulations, particularly with respect to carbohydrate quality, may confer sleep benefits. Future research may seek to evaluate the effectiveness of synergistic nutrient strategies to promote sleep quality, with particular attention to carbohydrate quality, quantity, and availability as well as carbohydrate to protein ratio.


Utility of cone-beam CT imaging in prostatic artery embolization.
To evaluate the utility of cone-beam computed tomography (CT) in patients undergoing prostatic artery (PA) embolization (PAE) for benign prostatic hyperplasia. From January 2012 to January 2013, 15 patients (age range, 59-81 y; mean, 68 y) with moderate- or severe-grade lower urinary tract symptoms, in whom medical management had failed were enrolled in a prospective United States trial to evaluate PAE. During pelvic angiography, 15 cone-beam CT acquisitions were performed in 11 patients, and digital subtraction angiography was performed in all patients. Cone-beam CT images were reviewed to assess for sites of potential nontarget embolization that impacted therapy, a pattern of enhancement on cone-beam CT suggesting additional PAs, confirmation of prostatic parenchymal perfusion before embolization, and contralateral prostatic parenchymal enhancement. Cone-beam CT was successful in 14 of 15 acquisitions, and PAE was successful in 14 of 15 patients (92%). Cone-beam CT provided information that impacted treatment in five of 11 patients (46%) by allowing for identification of sites of potential nontarget embolization. Duplicated prostatic arterial supply and contralateral perfusion were each identified in 21% of patients (three of 11). Prostatic perfusion was confirmed before embolization in 50% of acquisitions (seven of 14). Cone-beam CT is a useful technique that can potentially mitigate the risk of nontarget embolization. During treatment, it can allow for the interventionalist to identify duplicated prostatic arterial supply or contralateral perfusion, which may be useful when evaluating a treatment failure.


Numerical simulations of pyrite oxidation and acid mine drainage in unsaturated waste rock piles.
Numerical simulations of layered, sulphide-bearing unsaturated waste rock piles are presented to illustrate the effect of coupled processes on the generation of acid mine drainage (AMD). The conceptual 2D systems were simulated using the HYDRUS model for flow and the POLYMIN model for reactive transport. The simulations generated low-pH AMD which was buffered by sequential mineral dissolution and precipitation. Sulphide oxidation rates throughout the pile varied by about two orders of magnitude (0.004-0.4 kg m-3 year-1) due to small changes in moisture content and grain size. In the fine-grained layers, the high reactive surface area induced high oxidation rates, even though capillary forces kept the local moisture content relatively high. In waste rock piles with horizontal layers, most of the acidity discharged through vertical preferential flow channels while with inclined fine grained layers, capillary diversion channeled the AMD to the outer slope boundary, keeping the pile interior relatively dry. The simulation approach will be useful for helping evaluate design strategies for controlling AMD from waste rock.


Sarcomas in three generations of a family with neurofibromatosis.
The development of sarcomas in three generations of a family with neurofibromatosis (NF) is described. A 7-month-old boy developed a prostatic rhabdomyosarcoma. Family history revealed that his maternal grandmother had died of a malignant peripheral nerve sheath tumor at age 37 years and had been affected with neurofibromatosis. His mother (aged 36 years) has also developed a malignant peripheral nerve sheath tumor and NF has been confirmed in both mother and son. This family illustrates a cluster of sarcomas associated with NF and shows the importance of thorough investigation of reported family illnesses.


Technical variability of 2D gel electrophoresis - Application to soybean allergens.
Two-dimensional gel electrophoresis (2-DE) technique is used as a performing technique to assess the variability of protein expression in crops, and especially soybean endogenous food allergens, which are a subset of proteins of interest for assessing whether genetically modified (GM) soybean has a different allergenic profile compared to its non-GM counterpart. On top of the biological variability of the 2-DE, which has already been studied by several laboratories, technical variability has to be evaluated. In this study, several sources of variability (number of gel replicates, protein extracts, study timings and operators) were assessed qualitatively and quantitatively on all detectable polypeptide spots as well as on food allergen spots. Results showed that the major source of variability was the number of gel replicates. Other sources were minor. This has a direct practical impact on the laboratory work as this supports the utilization of three or four gel replicates to get robust results. Furthermore, this implies that the study can be run over several days, and be performed by several trained operators, without impacting its reproducibility. Furthermore, 2-DE could detect a 2-fold change between two samples with an acceptable rate of false positives (below 7%). This level of sensitivity is acceptable in the context of safety assessment of GM soybean as the biological variability of proteins in soybean is higher than the technical variability shown in this study. Overall, the 2-DE technique is suitable for investigating endogenous food allergen variability between several soybean seeds, including GM and non-GM counterpart.


Creating a pharmacy elective course in Indigenous health.
There is a critical need for greater Indigenous health education and cultural safety training for pharmacists. The objective of this paper is to describe the creation, development, and impact of Canada's first offering of an undergraduate elective course specific to pharmaceutical care in Indigenous health. A three-credit elective course was developed and offered to bachelor of science pharmacy students at the University of British Columbia. A variety of pedagogical approaches including reflection, educational trips, video conferencing with Indigenous communities, and Indigenous community-based projects were used. Evaluation of student learning impact included quantitative and qualitative post-course survey data, student enrollment, and student work. From course inception in 2012 to 2017, 101 students participated. Survey respondents rated an average of 4.7 out of 5 on the five core elements of the curriculum design and pedagogical practice (i.e. learning objectives, instructional methods, assessments, organization, and workload). Thematic analysis identified three themes: 1) the qualities of the course instructors, 2) the unique curriculum design and pedagogical practices, and 3) significant personal and professional impact on students. This course is one of few opportunities for pharmacy students to learn about cultural safety as it relates to the pharmaceutical care of Indigenous peoples. Extensive engagement with stakeholders and utilization of various teaching and assessment techniques were beyond the expected requirements of course offerings. Students highly rated this course as having personal and professional impact. This course plays a critical role in the overall Indigenization of pharmacy curricula.


Mechanisms of severe mitral regurgitation in mitral valve prolapse determined from analysis of operatively excised valves.
Certain clinical and mitral valvular morphologic findings are described in 83 patients (age 26 to 79 years [mean, 60]; 26 women [31%] and 57 men [69%]) with mitral valve prolapse (MVP) and mitral regurgitation (MR) severe enough to warrant mitral valve replacement. All 83 operatively excised valves were examined by the same person, and all excised valves had been purely regurgitant (no element of stenosis). No patients had hemodynamic evidence of dysfunction of the aortic valve. In each valve a portion of the posterior mitral leaflet was elongated such that the distance from the distal margin to basal attachment of this leaflet was similar to the distance from the distal margin of the anterior leaflet to its basal attachment to the left atrial wall. Two major mechanisms for the severe MR were found: dilatation of the mitral anulus with or without rupture of chordae tendineae and rupture of chordae tendineae with or without dilatation of the mitral anulus. Of the 83 patients, 48 (58%) had both dilated anuli (greater than 11 cm in circumference) and ruptured chordae tendineae; 16 (19%) had dilated anuli without ruptured chordae, and 16 (19%) had ruptured chordae without significant anular dilatation. In three patients the anulus was not dilated, nor were chordae ruptured, and therefore the mechanism of the MR is uncertain. Mitral chordal rupture was nearly as frequent in the 64 patients with clearly dilated anular circumferences as in the 19 patients with normal or insignificantly dilated anular circumferences (less than or equal to 11 cm).


[Clinical and genetic aspects of hypertrophic and dilated cardiomyopathy].
Primary cardiomyopathies are frequent heart diseases with an estimated prevalence of 0.3-0.4% in the general population, significantly contributing to systolic heart failure and sudden cardiac death in the young. Molecular genetic studies have identified 49 different disease genes for hypertrophic and dilated cardiomyopathy, often involving proteins of the sarcomere, the cardiac Z-disc and the cytoskeleton. With the development of new, advanced technologies based on next-generation sequencing, it is now possible to efficiently screen all known disease genes in an individual patient. The clinical workup of cardiomyopathies should always include the investigation of the patient's family to account for the familial aggregation of cardiomyopathies and identify diseased as well as asymptomatic carriers of mutations. The detection of specific genotypes facilitates diagnostic classification and can improve risk stratification in affected patients.


Cardiovascular responses to submaximal treadmill running in 11 to 13 year olds.
The influence of age, sex, maturity, body size and body fatness on cardiac output (Q) and stroke volume (SV) during treadmill running at 2.22 m x s(-1) was examined longitudinally. Mass, stature, triceps and subscapular skinfold thickness, and oxygen uptake (VO2) were recorded and Q was estimated using the CO2 rebreathing technique on each of three annual measurement occasions. Maturity was assessed using the indices for pubic hair described by Tanner. At the onset, subjects were 11.3 (0.4) y of age and data were available from a total of 274 Q determinations with equal numbers from boys and girls. Age-, sex- and maturity-associated changes in Q and SV adjusted for differences in body size and fatness were examined using multilevel regression modelling within an allometric framework. Changes in Q in both sexes were essentially in direct proportion to body surface area but, even with anthropometric variables controlled for, girls demonstrated a lower SV than boys, which was compensated for by a higher heart rate (HR) at each observation. At a given level of submaximal exercise over the age range 11-13 y Q is directly related to body size in both sexes. With body size and fatness controlled for, boys have greater SVs than girls when exercising at the same absolute VO2, Q and treadmill running speed. Age and maturation do not exert independent effects on either Q or SV.


Review of the analysis of 234Th in small volume (2-4 L) seawater samples: improvements and recommendations.
The short-lived radionuclide 234Th is widely used to study particle scavenging and transport from the upper ocean to deeper waters. This manuscript optimizes, reviews and validates the collection, processing and analyses of total 234Th in seawater and suggests areas of further improvements. The standard 234Th protocol method consists of scavenging 234Th from seawater via a MnO2 precipitate, beta counting, and using chemical recoveries determined by adding 230Th. The revised protocol decreases sample volumes to 2 L, shortens wait times between steps, and simplifies the chemical recovery process, expanding the ability to more rapidly and safely apply the 234Th method.


Neoadjuvant Sunitinib Decreases Inferior Vena Caval Thrombus Size and Is Associated With Improved Oncologic Outcomes: A Multicenter Comparative Analysis.
We analyzed outcomes of neoadjuvant sunitinib in patients with renal-cell carcinoma (RCC) and inferior vena caval (IVC) tumor and compared outcomes to patients who did not undergo neoadjuvant therapy before surgery. We performed a multicenter retrospective comparison of RCC patients with IVC tumor who underwent neoadjuvant sunitinib before surgery versus those who did not. Response to sunitinib was defined by Response Evaluation Criteria in Solid Tumors (RECIST). Primary outcome was cancer-specific survival. Secondary outcomes included overall survival. Multivariate analysis was performed to identify risk factors associated with primary and secondary outcomes. Kaplan-Meier analysis compared survival in neoadjuvant and primary surgery groups. Data of 53 patients were analyzed (19 neoadjuvant sunitinib, 34 primary surgery; median follow-up, 58 months). Eighteen (9 in each group, P = .143) had metastatic RCC. There was no difference in IVC tumor level between the 2 groups (P = .76). After neoadjuvant sunitinib, median primary tumor decreased size from 8.1 to 6.8 cm, and IVC tumor decreased by 1.3 cm. IVC tumor level decreased in 8 (42.1%) of 19 and was stable in 10 (52.6%) of 19; 5 (26.3%) of 19 experienced partial response. Similar proportions of patients underwent robot-assisted or minimally invasive approaches (P = .351), and no differences were noted in complications (P = .194). Multivariate analysis showed neoadjuvant sunitinib was associated with improved cancer-specific survival (odds ratio = 3.28; P = .021). Kaplan-Meier analysis demonstrated significantly longer median cancer-specific survival (72 vs. 38 months, P = .023) for neoadjuvant sunitinib. Neoadjuvant sunitinib was associated with a reduction in primary tumor and thrombus size as well as improved survival. Further investigation is needed to determine the utility of neoadjuvant sunitinib in RCC with IVC tumor.


Hydrochlorothiazide and Indapamide bind the NADPH binding site of bacterial Dihydrofolate Reductase: results of an in-silico study and their implications.
Hypertension is a public health concern. Low dose thiazide diuretics are known to effectively control blood pressure compared to that of other classes of antihypertensive drugs. In this context, we have performed an in-silico study and found that the two Sulphonamide Diuretics Hydrochlorothiazide and Indapamide bound the NADPH binding region of bacterial Dihydrofolate Reductase. Therefore, akin to Sulphonamide Antibiotics, Sulphonamide Diuretics may have antibiotic activity and thereby have the potential to modulate the gut microbiome in a way beneficial to vascular health. The in-silico experiment results were analyzed in the context of the relevant literature. We postulate that Sulphonamide Diuretics exert their antihypertensive role by modulating the gut microbiome, specifically by increasing butyrate-producing taxa in the gut. We recommend extending such work as it is plausible that Indapamide and other Sulphonamide Diuretics may be beneficial for both diabetes and hypertension.


An efficient protocol for genomic DNA extraction from formalin-fixed paraffin-embedded tissues.
Formalin-fixed paraffin-embedded tissues (FFPET) represent the largest source of archival biological material available for genomic studies. In this work we present an advanced protocol for extraction of high quality DNA from FFPET that can be applied in several molecular studies. Although cat mammary tumours (CMT) are the third most frequent tumour in cats the recovery of significant number of samples for molecular studies are in some way restricted to FFPET samples. We were able to obtain high quality DNA from FFPET of thirty six CMT that were subjected to pre-fixation and fixation processes routinely used in the veterinary hospitals. The quality of DNA obtained was tested by PCR amplification using six sets of primers that amplify single-copy fragments. The DNA fragments obtained were further sequenced. This protocol was able to provide FFPET gDNA that can be amplified and sequenced for larger fragments up to 1182bp.


The specificity of rat liver phospholipid methyltransferase for lyso derivatives and diacyl derivatives of phosphatidylethanolamine.
When sonicated suspensions of 1-palmitoyl-2-lysophosphatidyl-N-monomethylethanolamine (lysoPME) or 1-palmitoyl-2-lysophosphatidyl-N,N-dimethylethanolamine (lysoPDE) were incubated with rat liver microsomes and [Me-3H]AdoMet or [Me-14C]AdoMet, one methyl group was added to these lipids. With dipalmitoylphosphatidyl-N-monomethylethanolamine (PME) or dipalmitoylphosphatidyl-N,N-dimethylethanolamine (PDE) as substrates, enzymic monomethylation was also observed. However, the methylation of the lyso compounds was biphasic with an optimum at 0.75 mM lysoPME and 0.5 mM lysoPDE. In contrast to PME or PDE, the lysophospholipids produced a decrease in PC synthesis by lysoPME was reversible and was accompanied by an up to 4-fold increase in PDE synthesis. Competition experiments between lysoPME or lysoPDE and PME or PDE, together with kinetic studies, indicate a connection with methylation of both lyso- and diacylphospholipids. The same active site or sites in close proximity may serve for the second and third methylations. Hence, the presence of two acyl groups on the phospholipid molecule is not a prerequisite for N-methylation of this class of compounds. On the contrary, suspensions of phosphatidylethanolamine, or 2-lysophosphatidylethanolamine (lysoPE) with acyl chains of different degrees of saturation or with one alkenyl at the C1 position of the glycerol were not substrates for PE-N-methyltransferase; the lysoPEs were inhibitory above 0.5 mM.


Meta-HGT: Metapath-aware HyperGraph Transformer for heterogeneous information network embedding.
Heterogeneous information network embedding aims to learn low-dimensional node vectors in heterogeneous information networks (HINs), concerning not only structural information but also heterogeneity of diverse node and relation types. Most existing HIN embedding models mainly rely on metapath to define composite relations between node pairs and thus extract substructures from the original HIN. However, due to the pairwise structure of metapath, these models fail to capture the high-order relations (such as "Multiple authors co-authoring a paper") implicitly contained in HINs. To tackle the limitation, this paper proposes a Metapath-aware HyperGraph Transformer (Meta-HGT) for node embedding in HINs. Meta-HGT first extends metapath to guide the high-order relation extraction from original HIN and constructs multiple metapath based hypergraphs with diverse composite semantics. Then, Meta-HGT learns the latent node and hyperedge embeddings in each metapath based hypergraph through Meta-HGT layers. Each layer consists of two types of components, i.e., intra-hyperedge aggregation and inter-hyperedge aggregation, in which a novel type-dependent attention mechanism is proposed for node and hyperedge feature aggregation. Finally, it fuses multiple node embeddings learned from different metapath based hypergraphs via a semantic attention layer and generates the final node embeddings. Extensive experiments have been conducted on three HIN benchmarks for node classification. The results demonstrate that Meta-HGT achieves state-of-the-art performance on all three datasets.


Combined phacoemulsification surgery and intravitreal triamcinolone injection versus stand-alone surgery in patients with type 2 diabetes: a prospective randomized trial.
We would assess the efficacy of intravitreal injection of triamcinolone acetonide IVTA combined with standard phacoemulsification on the central subfield macular thickness (CSMT), the progression of diabetic retinopathy (DR), and the corrected distant visual acuity (CDVA) in type 2 diabetic patients. In this prospective single-blinded randomized clinical trial we recruited patients with type 2 diabetes who were eligible for cataract surgery. The patients were randomly assigned to two groups. The case group received an intravitreal IVTA at the end of phacoemulsification, and the control group had routine surgery. CSMT, progression of DR, CDVA, IOP, and adverse events including endophthalmitis were compared between the groups preoperatively and at 1, 3, and 6 months postoperatively. Among a total of 66 patients that were treated within the study period, 50 patients were included in the final analysis. The case group comprised 21 eyes, and the control group included 29 eyes. Regression models and corrected ANOVA test for repeated measures showed a significant reduction in CSMT at 3 and 6 months postoperatively, which was most significant when the preoperative CSMT was ≥300 μm, with a cut-off value of 347.3 μm in the case group (p < 0.000). DR progression was halted in the case group at 6 months with 52.38% of patients having their DR classified as moderate (P = 0.012). CDVA was significantly improved from baseline 6/60 (logMAR 1.0) pre-op to 6/6 (logMAR 0.00) at 6 months post-op in the case group, and from baseline 6/120 (logMAR 1.3) pre-op to 6/12 (logMAR 0.3) at 6 months post-op in the control group. The gain in visual acuity was significantly higher in the case group at all study points (p < 0.001). No significant rise in IOP was observed at any study point in both groups (p = 0.23 > 0.05). No endophthalmitis was recorded. Diabetic patients benefit significantly from cataract surgery. This study supports IVTA injection at the end of phacoemulsification in diabetic patients. Triamcinolone is an affordable (which is of particular importance in low-income countries as per our setting), and relatively safe "phaco-enhancer". NCT05413330. Initial release 10/06/2022. Unique Protocol ID: UDMS-Opthal-01-2022.


A review of basic science issues in low back pain.
This review article is based on a workshop, "New Horizons in Low Back Pain" that was held in November 1995 in San Diego, California. The current article follows the 1995 workshop format of a series of three case study models. Three classical clinical profiles were presented for consideration: lumbar radiculopathy, idiopathic (degenerative disk) low back pain, and degenerative stenosis. This article summarizes the basic science perspectives that were presented and discussed on each topic.


Attempts to conceive and the COVID-19 pandemic: data from the Apple Women's Health Study.
Previous studies have suggested that emergent events may affect pregnancy planning decisions. However, few have investigated the effect of factors related to the COVID-19 pandemic on pregnancy planning, measured by attempting conception, and how attempting conception status may differ by individual-level factors, such as social status or educational level. This study aimed to examine the effects of factors related to the COVID-19 pandemic, until March 2021, on attempting conception status and to assess the effect measure modification by educational level and subjective social status. We conducted a longitudinal analysis within a subgroup of 21,616 participants in the Apple Women's Health Study who enrolled from November 2019 to March 2021, who met the inclusion criteria, and who responded to the monthly status menstrual update question on attempting conception status (yes or no). Participants reporting hysterectomy, pregnancy, lactation, or menopause were excluded. We used generalized estimating equation methodology to fit logistic regression models that estimate odds ratios and 95% confidence intervals for the association between the proportion of participants attempting conception and the month of response (compared with a prepandemic reference month of February 2020) while accounting for longitudinal correlation and adjusting for age, race and ethnicity, and marital status. We stratified the analysis by social status and educational level. We observed a trend of reduced odds of attempting conception, with an 18% reduction in the odds of attempting conception in August 2020 and October 2020 compared with the prepandemic month of February 2020 (August odds ratio: 0.82 [95% confidence interval, 0.70-0.97]; October odds ratio: 0.82 [95% confidence interval, 0.69-0.97). The participants with lower educational level (no college education) experienced a sustained reduction in the odds of attempting to conceive from June 2020 to March 2021 compared with February 2020, with up to a 24% reduction in the odds of attempting to conceive in October 2020 (odds ratio, 0.76; 95% confidence interval, 0.59-0.96). Among participants that were college educated, we observed an initial reduction in the odds of attempting to conceive starting in July 2020 (odds ratio 0.73; 95% confidence interval, 0.54-0.99) that returned near prepandemic odds. Moreover, we observed a reduction in the odds of attempting to conceive among those with low subjective social status, with a decline in the odds of attempting to conceive beginning in July 2020 (odds ratio, 0.83; 95% confidence interval, 0.63-1.10) and continuing until March 2021 (odds ratio, 0.79; 95% confidence interval, 0.59-1.06), with the greatest reduction in odds in October 2020 (odds ratio, 0.67; 95% confidence interval, 0.50-0.91). Among women in the Apple Women's Health Study cohort, our findings suggested a reduction in the odds of attempting to conceive during the COVID-19 pandemic, until March 2021, particularly among women of lower educational level and lower perceived social status.


[The physiological and psychological mechanisms of infra-slow oscillation].
Infra-slow oscillation (ISO) is a kind of brain rhythm between 0.01 and 0.5 Hz. ISO is widely distributed in multiple brain regions. As an important psychophysiological activity, the ISO interacts with high-frequency neural rhythm via cross-frequency coupling, but has different activity patterns from high-frequency neural activity. Physiologically, the ISO may be generated by the dynamic activity of thalamus, glia, and ions. Psychologically, the frequency, amplitude, and phase of ISO could all regulate cognitive activities, but in different ways. Investigations on the ISO expands the neural rhythm research to lower frequency range, further promoting the construction of rhythmic theory of brain function.


The acquisition of parafoveal word information in reading.
A somewhat counterintuitive finding has emerged from experiments that restrict the "window" of visual information available on a fixation during reading: fixation duration increases even though there is less information to process on a fixation. The two most likely explanations for this phenomenon are: (1) that the reader extracts abnormal information outside the window and this slows down processing; (2) that a restricted window does not allow a preview of a word before it is fixated, and hence identification of the word is slower when the word subsequently is fixated. In the present experiments, these two alternatives were tested. Conditions in which the size of the window alternated between fixations were compared with conditions in which the size of the window remained constant from fixation to fixation. This manipulation allowed us to separate effects due to restriction of the size of the window on the current fixation from preview benefits (which would be due to restriction of the size of the window on the prior fixation). Two experiments demonstrated clear beneficial effects on fixation duration due to receiving a preview of a word on the fixation prior to when it was fixated. In contrast, restriction of the size of the window had only marginal effects on the fixation on which that restriction occurred. In addition, a subsidiary analysis suggested that the benefit of previewing a word was influenced by its length; for short words, a preview primarily allowed the reader to skip the word more frequently, whereas for longer words, a preview primarily shortened the fixation time on the word when it was later fixated.


Effect of the manipulation of oxyhemoglobin status by BW12C on tumor thermosensitivity and on blood flow in tumor and normal tissues in mice.
The effect of 70 mgkg-1 BW12C 30 min before heating on the thermosensitivity of RIF-1 leg tumors was studied. This schedule is known to increase the hypoxic fraction by a factor of 5. Heating, using a combined radio-frequency and saline bath technique, was for 30 min at 43, 43.5, and 44 degrees C and response was assayed by clonogenic cell survival immediately and 24 hr after treatment. BW12C did not alter RIF-1 thermosensitivity. The effects of heat up to 44 degrees C on the oxygen saturation curves of normal and BW12C-modified blood were compared and P50s were shown to rise from 36 to 52 mm Hg and 6.5 to 8.0 mm Hg respectively, showing the latter to be relatively resistant to right-shifting by heat. 86Rb extraction studies on BW12C-treated unheated animals showed that blood flow in leg and flank tumours 60 min after BW12C was reduced to 64% and 34% of control values respectively, indicating a further mechanism for induction of tumour hypoxia by BW12C. Blood flow in leg muscle, liver, and spleen was unchanged but in kidney and lung was increased to 127% and 119% of control respectively 60 min after BW12C.


Regeneration of Sn-Pb solder from waste printed circuit boards: A hydrometallurgical approach to treating waste with waste.
A green approach was introduced to regenerate Sn-Pb solder from waste printed circuit boards (PCBs). For this purpose, waste Al-based heat sinks were used as cementing agent to precipitate Sn and Pb from pregnant leach solution (PLS) obtained from the dissolution of waste PCBs in HCl. 97 % and 94.9 % of Sn and Pb were recovered, respectively, under optimum conditions at Al powder size of 300 μm, Al dosage of 1.516 g/l and reaction time of 15.41 min. Thermodynamic analysis was performed to predict the effect of temperature on the main reactions relevant to the cementation process. The structure of the Sn-Pb cement changed as function of temperature, leading to enhancement of the cementation rate via improving cathodic area. Kinetic modeling indicates that product layer diffusion is the rate limiting step for Sn and Pb cementation. However, the reaction mechanism shifted to chemical reaction control at high temperatures. The results of solder characterization indicated that the melting point of solder was 184.76 °C. The electrical resistivity and conductivity of the recovered pure alloy were measured to be 34.73 μΩ-cm and 2.88 × 106 Sm-1, respectively. The characterization revealed that the regenerated product is adequate as an alternative solder alloy.


Effects of plyometric- and cycle-based high-intensity interval training on body composition, aerobic capacity, and muscle function in young females: a field-based group fitness assessment.
High-intensity interval training (HIIT) is an effective alternative to moderate intensity continuous training for improvements in body composition and aerobic capacity; however, there is little work comparing different modalities of HIIT. The purpose of this study was to compare the effects of plyometric- (PLYO) and cycle-oriented (CYC) HIIT on body composition, aerobic capacity, and skeletal muscle size, quality, and function in recreationally trained females. Young (21.7 ± 3.1 yrs), recreationally active females were quasi-randomized (1:1 ratio) to 8 weeks of twice weekly PLYO (n = 15) or CYC (n = 15) HIIT. Body composition (four-compartment model), VO2peak, countermovement jump performance, muscle size, and echo intensity (muscle quality), as well as strength and power of the knee extensors and plantar flexors were measured before and after training. Both groups showed a similar decrease in body fat percentage (p < 0.001; η p 2 = 0.409) and echo intensity (p < 0.001; η p 2 = 0.558), and an increase in fat-free mass (p < 0.001; η p 2 = 0.367) and VO2peak (p = 0.001; η p 2 = 0.318). Muscle size was unaffected (p > 0.05), whereas peak torque was reduced similarly in both groups (p = 0.017; η p 2 = 0.188) and rapid torque capacity was diminished only for the knee extensors after CYC (p = 0.022; d = -0.67). These results suggest that PLYO and CYC HIIT are similarly effective for improving body composition, aerobic capacity, and muscle quality, whereas muscle function may express moderate decrements in recreationally active females. ClinicalTrials.gov (NCT05821504).


Hounsfield Unit as a Predictor of Adjacent-Level Disease in Lumbar Interbody Fusion Surgery.
Bone density has been associated with a successful fusion rate in spine surgery. Hounsfield units (HUs) have more recently been evaluated as an indirect representation of bone density. Low preoperative HUs may be an early indicator of global disease and chronic process and, therefore, indicative of the need for future reoperation. To assess preoperative HUs and their association with future adjacent segment disease requiring surgical intervention through retrospective study. Patients who underwent lumbar interbody fusion at a single institution between 2007 and 2016 were retrospectively reviewed. Hounsfield unit values were measured from preoperative computed tomography (CT) using sagittal images, encircling cancellous portion of the vertebral body. Patient charts were reviewed for follow-up data and adjacent-level disease development. A total of 793 patients (age: 56.1 ± 13.7 years, 54.4% female) were included in this study. Twenty-two patients required surgical intervention for adjacent segment disease. Patients who underwent lumbar interbody fusion and did not subsequently require surgical intervention for adjacent-level disease were found to have a higher mean preoperative HU than patients who did require reoperation (180.7 ± 70.0 vs 148.4 ± 8.1, P = .032). Preoperative CT HU was a significant independent predictor for the requirement of adjacent-level surgery after spinal arthrodesis (odds ratio = 0.891 [0.883-0.899], P = .029). Patients who underwent lumbar interbody fusion that did not require reoperation for adjacent-level degeneration were found to have a higher mean preoperative HU than patients who did require surgical intervention. Lower preoperative CT HU was a significant independent predictor for the requirement of adjacent-level surgery after spinal arthrodesis.


Abnormal uterine bleeding as a presentation of metastatic breast disease in a patient with advanced breast cancer.
Extragenital carcinomas secondarily involving the uterus are very rare and they usually occur as a manifestation of widespread disease. When the metastases involve the endometrium in a diffuse, permeative pattern, sparing the glands, they may cause problems in the diagnosis. A case of metastatic carcinoma to the endometrium with a decidua-like pattern is reported. The patient had a history of breast carcinoma and presented with vaginal bleeding. The pathologic findings in the uterine curettings raised the differential diagnosis between metastatic breast carcinoma and non-neoplastic stromal lesions. The presence of nuclear atypia and mitotic activity along with the appropriate immunohistochemical findings revealed the neoplastic nature of the endometrial lesion and confirmed its origin from the breast. Unusual uterine bleeding in a patient with breast cancer should alert the gynecologist to the possibility of metastatic breast disease. Furthermore, the metastasis to the uterus and to other organs of the genital tract can be considered as a preterminal event.


Association of Motoric Cognitive Risk Syndrome with Cardiovascular and Noncardiovascular Factors: A Systematic Review and Meta-Analysis.
Motoric cognitive risk syndrome (MCR) is a recently proposed predementia syndrome characterized by subjective cognitive impairment and slow gait. We aim to assess the cardiovascular and noncardiovascular factors associated with MCR. Systematic review and meta-analysis. Studies comparing patients with MCR to those without MCR, and identifying the factors associated with MCR. We used databases, including PubMed, Cochrane CENTRAL, and Embase, to identify studies evaluating the factors associated with MCR. Mean differences, odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) with 95% CIs were calculated using Review Manager. Meta-analysis revealed that all cardiovascular factors, including diabetes (21 studies; OR 1.50, 95% CI 1.37, 1.64), hypertension (21 studies; OR 1.20, 95% CI 1.08, 1.33), stroke (16 studies; OR 2.03, 95% CI 1.70, 2.42), heart disease (7 studies; OR 1.45, 95% CI 1.13, 1.86), coronary artery disease (5 studies; OR 1.49, 95% CI 1.16, 1.91), smoking (13 studies; OR 1.28, 95% CI 1.04, 1.58), and obesity (12 studies; OR 1.34, 95% CI 1.13, 1.59) were significantly higher in the MCR than the non-MCR group. Noncardiovascular factors, including age (22 studies; MD = 1.08, 95% CI 0.55, 1.61), education (8 studies; OR 2.04, 95% CI 1.28, 3.25), depression (17 studies; OR 2.19, 95% CI 1.65, 2.91), prior falls (9 studies; OR 1.45, 95% CI 1.17, 1.80), arthritis (6 studies; OR 1.35, 95% CI 1.07, 1.70), polypharmacy (5 studies; OR 1.65, 95% CI 1.07, 2.54), and sedentary lifestyle (11 studies; OR 2.00, 95% CI 1.59, 2.52), were significantly higher in the MCR than in the non-MCR group. Alcohol consumption (6 studies; OR 0.84, 95% CI 0.72, 0.98), however, favored the MCR over the non-MCR group. Additionally, there was no significant association of MCR with gender (22 studies; OR 1.04, 95% CI 0.94, 1.15) and cancer (3 studies; OR 2.39, 95% CI 0.69, 8.28). MCR was also significantly associated with an increased likelihood of incident dementia (5 studies; HR 2.84, 95% CI 1.77, 4.56; P < .001), incident cognitive impairment [2 studies; adjusted hazard ratio (aHR) 1.76, 95% CI 1.44, 2.15], incident falls (4 studies; RR 1.37, 95% CI 1.17, 1.60), and mortality (2 studies; aHR 1.58, 95% CI 1.35, 1.85). MCR syndrome was significantly associated with diabetes, hypertension, stroke, obesity, smoking, low education, sedentary lifestyle, and depression. Moreover, MCR significantly increased the risk of incident dementia, cognitive impairment, falls, and mortality.


Eosinophilic Esophagitis: Etiology and Therapy.
Eosinophilic esophagitis (EoE) is a relatively recently identified but now frequently encountered antigen/immune-mediated disease which places significant burden on patients and the healthcare system. With its growing prevalence and recognition by healthcare providers in multiple disciplines, substantial progress has been made regarding the diagnostic criteria, clinical evaluation, tools for disease assessment, and immune pathways related to pathogenesis. Current treatment goals focus on the amelioration of inflammation and prevention of remodeling consequences using proton pump inhibitors, swallowed topical steroids, elimination diets, and esophageal dilation. Ongoing research holds promise for more efficacious and targeted therapies as well as a personalized approach to the care of patients with EoE.


Intrathecal synthesis of beta-2-microglobulin in multiple sclerosis and aseptic meningo-encephalitis.
Beta-2-microglobulin (beta 2m) levels were studied in the cerebrospinal fluid (CSF) and plasma of 52 patients with clinically definite multiple sclerosis (MS) and of 14 with aseptic meningo-encephalitis (AM). Reference values for beta 2m were defined in 72 subjects of different age groups with tension headache (TH). Plasma levels of beta 2m increased with age in TH controls, particularly in the older age group, while no significant age variation could be detected for CSF beta 2m. Increased levels of beta 2m were found in the CSF and plasma of AM patients and in the CSF in MS. Calculations of CSF/plasma beta 2m ratios showed higher values in AM, reflecting intrathecal beta 2m synthesis, while only borderline alterations were evident in MS. Demonstration of intrathecal production of beta 2m is an additional CSF finding that may be useful in evaluating, among others, inflammatory nervous system disorders, but it has limited importance in the study of MS patients.


Glial cells in (patho)physiology.
Neuroglial cells define brain homeostasis and mount defense against pathological insults. Astroglia regulate neurogenesis and development of brain circuits. In the adult brain, astrocytes enter into intimate dynamic relationship with neurons, especially at synaptic sites where they functionally form the tripartite synapse. At these sites, astrocytes regulate ion and neurotransmitter homeostasis, metabolically support neurons and monitor synaptic activity; one of the readouts of the latter manifests in astrocytic intracellular Ca(2+) signals. This form of astrocytic excitability can lead to release of chemical transmitters via Ca(2+) -dependent exocytosis. Once in the extracellular space, gliotransmitters can modulate synaptic plasticity and cause changes in behavior. Besides these physiological tasks, astrocytes are fundamental for progression and outcome of neurological diseases. In Alzheimer's disease, for example, astrocytes may contribute to the etiology of this disorder. Highly lethal glial-derived tumors use signaling trickery to coerce normal brain cells to assist tumor invasiveness. This review not only sheds new light on the brain operation in health and disease, but also points to many unknowns.


Effect of probenecid on the renal excretion mechanism of a new carbapenem, DA-1131, in rats and rabbits.
The effects of probenecid, an anion transport inhibitor, on the renal excretion mechanism of a new anionic carbapenem, DA-1131, were investigated after a 1-min intravenous infusion of DA-1131 at 100 mg/kg of body weight to rabbits and 50 mg/kg to rats with or without probenecid at 50 mg/kg for both species. In control rabbits, the renal clearance (CLR) of DA-1131 and the glomerular filtration rate based on creatinine clearance (CLCR) were 6.14 +/- 2.09 and 2.26 +/- 0.589 ml/min/kg, respectively. When considering the less than 10% plasma protein binding of DA-1131 in rabbits, renal tubular secretion of DA-1131 was observed in rabbits. The CLR of DA-1131 (3. 87 +/- 0.543 ml/min/kg) decreased significantly with treatment with probenecid in rabbits, indicating that the renal tubular secretion of DA-1131 was inhibited by probenecid. However, in control rats, the CLR of DA-1131 (5.80 +/- 1.94 ml/min/kg) was comparable to the CLCR (4.29 +/- 1.64 ml/min/kg), indicating that DA-1131 was mainly excreted by glomerular filtration in rats. Therefore, it could be expected that the CLR of DA-1131 could not be affected by treatment with probenecid in rats; this was proved by a similar CLR of DA-1131 with treatment with (6.93 +/- 0.675 ml/min/kg) or without (5.80 +/- 1.94 ml/min/kg) probenecid. Therefore, the renal secretion of DA-1131 is a factor in rabbits but is not a factor in rats.


The evolution of hypospadias publications: A bibliometric approach.
Although the increasing prevalence of hypospadias has been reported in many countries, there is a lack of bibliometric studies that make a holistic assessment of the publications about this issue. This study aims to make a holistic evaluation, latest developments, and trend topics about hypospadias publications between 1980 and 2018 through bibliometric analysis. All the publications about hypospadias published in the Web of Science index between 1980 and 2018 were downloaded and analyzed using bibliometric methods. The Spearman's correlation coefficient was utilized to analyze the correlations between economic productivity and performance of the countries on hypospadias. Linear regression analysis was performed to estimate the number of publications for the following years. Bibliometric analyses were performed with 1940 articles. With 527 (27.2%) publications, the USA was the country that made the most contribution to the literature. The top active 3 journals were the Journal of Urology, Journal of Pediatric Urology, and Urology. A high correlation was detected between hypospadias publication productivity and GDP (r=0.791, p<0.001). The regression analysis results showed that the expected number of articles to be produced was 95 (75-116) for 2019 and 106 (47-164) for 2024. This study provides a holistic evaluation of the articles about hypospadias, which is an anomaly that should be repaired and treated with surgery due to its potential problems for the children at kindergarten and school age. Increasing the collaboration between especially developing countries and research in different countries with samples from different communities through multidisciplinary studies are recommended.


Morphologic characteristics of macroscopic peritoneal finding in patients with peritoneal dialysis.
Peritoneal dialysis (PD) has been an attractive treatment for end-stage kidney disease. Long-term exposure to the PD solution creates functional and morphological alterations, and these alterations diminish the efficacy of PD. It is important to establish an evaluation of the changes in PD patients and strategies for the prevention of PD damage and encapsulating peritoneal sclerosis (EPS). We determined the relationship between clinical findings and macroscopic morphological findings by laparoscopy in patients receiving PD. Macroscopic intraperitoneal findings were recorded at the PD catheter removal in 23 PD patients. We examined macroscopic morphological findings such as fibrin deposition, peritoneal turbidity, vasculopathy, adhesion and calcification in both parietal and visceral peritoneum of upper and lower peritoneal cavities, and assessed the score semi-quantitatively. We then evaluated the relationship between the morphological score and clinical findings, especially observational parts and findings in EPS patients. The total macroscopic score increased with PD duration. Peritoneal turbidity, fibrin deposition, and calcification were observed in the whole peritoneal cavity. Scores of fibrin deposition, turbidity, and calcification increased with PD duration. Vasculopathy in the parietal peritoneum was more serious compared with that in the visceral peritoneum, but there was no difference in the vasculopathy between the upper and lower areas. A characteristic of the macroscopic findings in EPS patients was peritoneal calcification in this study. It appears that macroscopic findings using laparoscopy is significant in evaluating the degree of the peritoneum damage and predicting EPS development.


Some possibilities to reduce the biofilm formation on transparent siloxane coatings.
Presence of biofilms is a significant problem to a variety of industrial areas, underwater sensors, shipping, etc. Therefore solutions are sought to inhibit biofilm formation and to permit biofilm removal. Surface modification by suitable coating could be one of them. The present study reports the potential of new transparent biocides-free siloxane antifouling coatings, containing low toxic additives, such as TiO(2) nanoparticles, surfactants and antioxidants, to reduce biofilm formation in mimicking marine environment, laboratory conditions. As evaluated with several parameters: chlorophyll content, carotenoids content, total protein and total dry mass, the biofilm formation was most sharply reduced by the composition coatings containing non-ionic surfactant, super spreader Y17112, followed by those containing antioxidant, α-tocopherol. Depending on the amount of the super spreader (0.1-1.0 wt.%) and the tested parameter, approximately 3-8-fold reduction was observed in the biofilm formation. It is supposed, that the effect of the studied additives, both surfactant and antioxidant, is due to some inhibition of the adhesive extra cellular substances cross-linking with impact onto the biofilm cohesion strength and its adhesion.


Phoamtonic designs yield sizeable 3D photonic band gaps.
We show that it is possible to construct foam-based heterostructures with complete photonic band gaps. Three-dimensional foams are promising candidates for the self-organization of large photonic networks with combinations of physical characteristics that may be useful for applications. The largest band gap found is based on 3D Weaire-Phelan foam, a structure that was originally introduced as a solution to the Kelvin problem of finding the 3D tessellation composed of equal-volume cells that has the least surface area. The photonic band gap has a maximal size of 16.9% (at a volume fraction of 21.6% for a dielectric contrast [Formula: see text]) and a high degree of isotropy, properties that are advantageous in designing photonic waveguides and circuits. We also present results for 2 other foam-based heterostructures based on Kelvin and C15 foams that have somewhat smaller but still significant band gaps.


Granular flow experiment using artificial gravity generator at International Space Station.
Studying the gravity-dependent characteristics of regolith, fine-grained granular media covering extra-terrestrial bodies is essential for the reliable design and analysis of landers and rovers for space exploration. In this study, we propose an experimental approach to examine a granular flow under stable artificial gravity conditions for a long duration generated by a centrifuge at the International Space Station. We also perform a discrete element simulation of the granular flow in both artificial and natural gravity environments. The simulation results verify that the granular flows in artificial and natural gravity are consistent. Further, regression analysis of the experimental results reveals that the mass flow rate of granular flow quantitatively follows a well-known physics-based law with some deviations under low-gravity conditions, implying that the bulk density of the granular media decreases with gravity. This insight also indicates that the bulk density considered in simulation studies of space probes under low-gravity conditions needs to be tuned for their reliable design and analysis.


Induction of ornithine decarboxylase in the liver and spleen of mice by interleukin 1-like factors produced from a macrophage cell line.
Injection of culture medium of P388D1 cells, a murine macrophage cell line, into mice produced a rapid induction of ornithine decarboxylase in the liver and spleen. The ornithine decarboxylase-inducing factor in the medium was purified by gel-filtration and chromatofocusing. With these procedures, the factor was usually found in the fraction of interleukin 1 (a lymphocyte-activating factor), indicating that the factor is identical with interleukin 1 or a molecule closely related to interleukin 1. The ornithine decarboxylase induction by the factor was suppressed by cycloheximide, but actinomycin D did not suppress the induction, or rather enhanced it. These findings may provide valuable information on the important roles of macrophages in immune responses or in inflammatory reactions.


Effects of ketoconazole on rat testicular steroidogenic enzymatic activities.
Ketoconazole (K) is an antifungal imidazole derivative which has been shown to be a potent inhibitor of testosterone (T) biosynthesis in rodents and humans. To study the effect of K on rat testicular steroidogenesis we measured the activities of five testicular microsomal steroidogenic enzymes in K-treated rats and controls. Thirty male adult rats were given either 2 mg K or water every 12 hours by mouth during 5 days. Mean testicular weight was similar in both groups of animals. The K-treated group had a T serum concentration of 83 +/- 14 ng/dL whereas it was 94 +/- 16 ng/dL in the control group (NS). The K-treated animals had decreased activities of the 3 beta-hydroxysteroid dehydrogenase (830 +/- 48 vs 2,245 +/- 109 pmol/mg protein/min, P less than 0.001), 17-hydroxylase (243 +/- 5 vs 676 +/- 17 pmol/mg protein/min, P less than 0.001), 17-ketosteroid reductase (31 +/- 2 vs 169 +/- 7 pmol/mg protein/min, P less than 0.001), and aromatase enzymes (92 +/- 6 vs 123 +/- 7 pmol/mg protein/min, P less than 0.01). The 17,20-desmolase activity was similar in both groups of animals (210 +/- 4 vs 171 +/- 18 pmol/mg protein/min). We conclude that K given orally to rats inhibits the activity of several testicular steroidogenic enzymes.


Breast ductal carcinoma with osseous metaplasia.
The case of an elderly patient with one of the rarest forms of breast carcinoma is reported. Histomorphologic aspects and theories as to its origin are discussed.


Varied actions of proinflammatory cytokines on excitotoxic cell death in the rat central nervous system.
Interleukin (IL)-1beta mediates diverse forms of neurodegeneration and exacerbates cell death induced by striatal injection of the excitotoxin alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) in the rat brain. The objective of this study was to determine whether this effect was specific to IL-1beta. Injection of IL-1alpha and AMPA in the striatum had effects identical to those of IL-1beta, whereas coinjection of IL-6 or tumor necrosis factor (TNF)-alpha with AMPA failed to induce significant cortical cell death. In contrast to IL-1alpha, IL-1beta, and IL-6, TNFalpha significantly reduced (by 38%) the local striatal damage. These findings suggest that the effect of IL-1 on AMPA receptor-mediated cell death in the rat striatum is not mimicked by other proinflammatory cytokines. Furthermore, TNFalpha shows neuroprotective effects against acute excitotoxic injury.


Increased atherosclerotic lesions in LDL receptor deficient mice with hematopoietic nuclear receptor Rev-erbα knock- down.
Nuclear receptor Rev-erbα plays important roles in circadian clock timing, lipid metabolism, adipogenesis, and vascular inflammation. However, the role of Rev-erbα in atherosclerotic lesion development has not been assessed in vivo. The nuclear receptor Rev-erbα was knocked down in mouse haematopoietic cells by means of shRNA-lentiviral transduction, followed by bone marrow transplantation into LDL receptor knockout mice. The Rev-erbα protein in peripheral macrophage was reduced by 70% as compared to control mice injected with nontargeting shRNA lentivirus-transduced bone marrow. A significant increase in atherosclerotic lesions was observed around the aorta valves as well as upon en face aorta analysis of Rev-erbα knock-down bone marrow recipients (P<0.01) as compared to the control mice, while plasma cholesterol, phospholipid, and triacylglycerol levels were not affected. Overexpression of Rev-erbα in bone marrow mononuclear cells decreased inflammatory M1 while increasing M2 macrophage markers, while Rev-erbα knock down increased the macrophage inflammatory phenotype in vitro and in vivo. Furthermore, treatment of differentiating macrophages with the Rev-erbα ligand heme promoted expression of antiinflammatory M2 markers. These observations identify hematopoietic cell Rev-erbα as a new modulator of atherogenesis in mice.


Comparison of metal on metal versus polyethylene-ceramic bearing in uncemented total hip arthroplasty in patients with haemophilic arthropathy.
We report the results of a consecutive series of 12 cases with haemophilic hip arthropathy treated with uncemented total hip arthroplasty (THA). Our hypothesis was that THA results in the haemophilic group would be inferior to those in the nonhaemophilic group. The clinical histories of 12 consecutive THAs in eight patients (all men) with hereditary bleeding disorders (haemophilia A and B and von Willebrand disease) were reviewed retrospectively. The results were compared with an age- and sex-matched control group without haemophilia, with special emphasis on bearing surfaces (Metasul metal-on-metal; polyethylene-ceramic articulation). The mean follow-up of the control group was 9.7 (range five to 24) years and was similar to the haemophilia group, with 10.4. Survival in the Metasul haemophilic group was 22.2 % after 18 years, which significantly differed from the Metasul control group (100 % after 24 years). Survival of the polyethylene-ceramic haemophilic group was similar to the control group (100 % after seven years in both groups). The metal-on-metal bearing surface in patients with haemophilia gave inferior results compared with nonhaemophilic patients. The use of metal-on-metal bearings in haemophilia is debatable.


Incidental gallbladder cancer after routine cholecystectomy: when should we suspect it preoperatively and what are predictors of patient survival?
In about 1% of cases, incidental gallbladder cancers (iGBC) are found after routine cholecystectomy. The aim of this study is to compare clinical features of iGBC with benign GB disease and to evaluate factors affecting recurrence and survival. Between January 1998 and March 2014, 4,629 patients received cholecystectomy and 73 iGBC patients (1.6%) were identified. We compared clinical features of 4,556 benign GB disease patients with 73 iGBC patients, and evaluated operative outcomes and prognostic factors in 56 eligible patients. The iGBC patients were older and concomitant diseases such as hypertension and anemia were more common than benign ones. And an age of more than 65 years was the only risk factor of iGBC. Adverse prognostic factors affecting patients' survival were age over 65, advanced histology, lymph node metastasis, and lymphovascular invasion on multivariate analysis. Age over 65 years, lymph node involvement, and lymphovascular invasion were identified as unfavorable factors affecting survival in subgroup analysis of extended cholecystectomy with bile duct resection (EC with BDR, n = 22). Prior to routine cholecystectomy, incidental GB cancer should be suspected especially in elderly patients. And advanced age, lymph node metastasis, and lymphovascular invasion are important prognostic factors in EC with BDR cohorts.


Purification and identification of photoreceptor guanylate cyclase.
Photoreceptor guanylate cyclase was solubilized and purified from bovine rod outer segments with 50-150-fold increase in specific activity using the nonionic detergent n-dodecyl-beta-D-maltoside. Guanylate cyclase activities correlated with the enrichment of a protein with an apparent Mr = 112,000. The purified enzyme showed specific activities of 100-700 nmol of cGMP produced/min/mg protein and exhibited positive cooperativity with respect to MnGTP (Hill coefficient n = 1.6 +/- 0.1). The apparent Km was 274 +/- 67 microM, and the turnover number was determined to be 0.2-1.3 cGMP produced/s. The molar ratio of the 112-kDa protein to rhodopsin corresponds to 1:104. This indicates that the amount of guanylate cyclase in rod photoreceptors is nearly equimolar to the amount of the phosphodiesterase.


Comparative Evaluation of Vestibular Incision Subperiosteal Tunnel Access (VISTA) Technique With and Without Advanced Platelet-Rich Fibrin for Treatment of Maxillary Anterior Gingival Recessions.
Gingival recession is an apical shift of the gingival margin with exposure of the root surface to the oral cavity, which creates an esthetic problem. The present study was attempted to compare vestibular incision subperiosteal tunnel access (VISTA) with and without advanced platelet-rich fibrin (A-PRF) in the treatment of Miller Class I gingival recessions. A total of 24 patients were assigned randomly to either the test group (VISTA with A-PRF) or the control group (VISTA alone). Clinical parameters like recession depth, recession width, clinical attachment loss, width of keratinized gingiva, gingival thickness, and probing depth were recorded at baseline and at 3 and 6 months postoperatively. Intergroup comparison of mean root coverage (RC) in mm, %RC, change in width of keratinized gingiva and clinical attachment gain revealed no statistically significant difference (P > .05). Change in gingival thickness showed statistically significant improvement in test group. Within the limitations of this study, both treatment options (VISTA with A-PRF and VISTA alone) have resulted in predictable and comparable RC, with increased gingival thickness in the test group.


Evidence for extreme climatic warmth from late cretaceous arctic vertebrates
A Late Cretaceous (92 to 86 million years ago) vertebrate assemblage from the high Canadian Arctic (Axel Heiberg Island) implies that polar climates were warm (mean annual temperature exceeding 14 degreesC) rather than near freezing. The assemblage includes large (2.4 meters long) champsosaurs, which are extinct crocodilelike reptiles. Magmatism at six large igneous provinces at this time suggests that volcanic carbon dioxide emissions helped cause the global warmth.


Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3.
The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC50 values of 0.61 ± 0.02 and 0.58 ± 0.12 μmol/L against TEAD1 and TEAD3, respectively. Further chemical optimization based on DC-TEAD in 1072 yielded a selective TEAD3 inhibitor DC-TEAD3in03 with the IC50 value of 0.16 ± 0.03 μmol/L, which shows 100-fold selectivity over other TEAD isoforms in activity-based protein profiling (ABPP) assays. In cells, DC-TEAD3in03 showed selective inhibitory effect on TEAD3 in GAL4-TEAD (1-4) reporter assays with the IC50 value of 1.15 μmol/L. When administered to zebrafish juveniles, experiments showed that DC-TEAD3in03 reduced the growth rate of zebrafish caudal fins, indicating the importance of TEAD3 activity in controlling proportional growth of vertebrate appendages.


Elevated levels of miR-210 correlate with anemia in β-thalassemia/HbE patients.
Ineffective erythropoiesis in β-thalassemia patients is caused by the premature death of red blood cell precursors due to excess α-globin chains. As a consequence, patients develop chronic anemia and hypoxia. Upregulation of miR-210, a hypoxia-induced miRNA, has been shown to regulate globin gene expression and erythroid differentiation in β-thalassemia/HbE erythroid progenitor cell culture. The present study examined whether the expression of miR-210 in circulation reflects the anemic condition in these patients. The level of miR-210 expression was directly examined from red blood cells and plasma of β-thalassemia/HbE patients. Transferrin receptor, a marker of erythropoiesis activity, was also analyzed. Increased expression of both red blood cells and plasma miR-210 as well as elevated levels of serum transferrin receptor in β-thalassemia/HbE patients were observed when compared to those of normal individuals (p < 0.05). In addition, red blood cell miR-210 level was inversely correlated with hemoglobin levels (r = -0.7054, p < 0.01) and hematocrit (r = -0.6017, p < 0.05). The higher expression of miR-210 in these patients may be the consequence of hypoxia occurring from the lower hemoglobin level. Thus, analysis of red blood cell miR-210 may be useful as a method for assessing hypoxia in β-thalassemia patients.


1H-MRS Quantitation of Age-Dependent Taurine Changes in Mouse Brain.
A mouse model of Alzheimer's disease demonstrates reduced beta-amyloid levels in the whole brain, associated with a gain of hippocampal memory, after drinking taurine-enriched water; this suggests that a taurine supplement could be a promising treatment for cognitive deficit. The objective of this study is to establish a methodology for quantifying taurine in the whole brain, taking advantage of the rapid development of non-invasive imaging techniques such as magnetic resonance imaging and magnetic resonance spectroscopy (MRS). Single-voxel proton MRS was used to obtain quantifiable taurine peaks at 3.25 and 3.43 ppm. Quantitative MRS results were obtained in C57BL/6 mice of various age groups: 4, 11, 18, and 27 months old. Compared with the 4-month-old group, taurine levels dropped significantly only at 27 months of age (p = 0.03). However, a significant decrease of N-acetyl-aspartate (NAA) in the brain was observed at both 18 and 27 months (p = 0.03 and p = 0.02). In addition, MRS-measured taurine level is highly correlated with hippocampal volume (r = 0.95). These results suggest that decreased taurine levels in the brain could be used as biomarkers for hippocampal changes and are fully translatable into putative cognitive loss in both animal models and human studies without the ex vivo approach.


Differential regulation of Wnt/beta-catenin signaling by Liver X Receptors in Schwann cells and oligodendrocytes.
Oxysterols are reactive molecules generated by the oxidation of cholesterol. Their implication in cholesterol homeostasis and in the progression of neurodegenerative disorders is well known. Here, we study the role of oxysterols and their nuclear receptors, Liver X Receptor (LXR), in myelinating glial cells of the central and peripheral nervous systems. First, we show by gas chromatography/mass spectrometry that the brain, sciatic nerve, oligodendrocytes and Schwann cells contain 24(S)-hydroxycholesterol, 25-hydroxycholesterol (25-OH) and 27-hydroxycholesterol, and they express their biosynthetic enzymes. We observed a differential effect of 25-OH toward myelin genes (MPZ and PMP22) expression: 25-OH inhibits MPZ and PMP22 in Schwann cell line but not in oligodendrocyte cell line. Importantly, the invalidation of LXR in mice enhanced MPZ and PMP22 transcripts expression in the sciatic nerve, but inhibited their expression in the brain. We have previously reported that Wnt signaling pathway is crucial for myelin gene expression. We show that the transcripts of Wnt components (Disheveled, TCF3, beta-catenin) are strongly repressed by oxysterols in Schwann cells but are activated in oligodendrocytes. Furthermore, we show by immunofluorescent labeling that beta-catenin is re-localized on the level of the Golgi apparatus of Schwann cells after incubation with 25-OH. We did not observe such an unusual localization of beta-catenin in oligodendrocytes. Our findings reveal a complex cross-talk between LXR and Wnt/beta-catenin pathway in myelinating glial cells.


Overuse injuries of the lower extremity.
Overuse injuries are a common and important cause of morbidity in elite and recreational athletes. They are increasingly recognized in the sedentary population. This article reviews the major classes of overuse injuries of the lower extremity. The underlying pathologic condition is correlated with the imaging appearances, and the often variable relationship between the imaging appearances and patients' symptoms are reviewed. Attempts at imaged-based grading systems and the ability of imaging to predict patients' prognosis are considered. Image-guided injection therapy for tendinopathy is an important and rapidly changing area; the indications, risks, and potential benefits of these interventions are reviewed.


A simplified modification of a reconstruction plate into a mandibular transport distraction device: A technical note.
Transport distraction is nowadays gaining enormous popularity and is becoming a promising option for reconstruction of mandibular defects. However, the vast number of distraction device designs create huge confusion in the clinician's mind to choose the right one. Considering these complex and costly designs, the authors decided to find a simplified way of combining a modified conventional reconstruction plate and monofocal distraction device that can act as a transport distraction device for bridging of bony defects. A case performed by this technique and device has been presented along with the description of device design.


Antecedents of behavioral intentions for purchasing safety tools among women.
The rise of crimes and violence against women are evident worldwide. The self-protection and behavioral aspects however are underexplored. The need for assessment for safety such as the purchasing intentions of safety tools should be considered to promote the mitigation and reduction of violence and crimes against women, may it be in households or outdoors. This study aimed to holistically analyze the determinants of behavioral intentions to purchase self-defense tools among women. Focusing on the Philippines, the structural equation modeling considering the extended theory of planned behavior (TPB) and protection motivation theory (PMT) integrated model was completely analyzed. A total of 553 valid respondents were purposively gathered to completely assess the behavioral domains and protective behaviors of women. From the results, self-efficacy showed the most significant factor affecting purchasing intentions, followed by behavioral intentions, and the behavioral domains under TPB. Moreover, indirect effects of PMT variables to purchasing intentions were seen; highest from understanding of safety, perceived risk, and then perceived severity. The extended latent variable such as perceived safety showed an indirect effect while buying impulse showed a direct significant effect on purchasing intentions. This is considered as the first study that assessed the different variables affecting purchasing intentions of self-defense tools. The findings of this study would provide a gateway as benchmark for how women feel, behave, and seeks protection. Implementing the suggestion with other aspects would end up promoting the overall safety of a country, not just for women, but for all victims against crime and violence.


A facile approach to fabricate porous nanocomposite gels based on partially hydrolyzed polyacrylamide and cellulose nanocrystals for adsorbing methylene blue at low concentrations.
Porous nanocomposite gels were fabricated by a facile method consisting of the electrospinning and subsequent heat treatment based on partially hydrolyzed polyacrylamide (HPAM) of ultra-high molecular weight, with cellulose nanocrystals (CNCs) as crosslinker. The effects of three electrospinning parameters (i.e., solution concentration, composition of solvent mixture, and CNC loading level) on morphology and diameter of electrospun fibers were systematically investigated. The swelling properties of porous gels and their application in the removal of methylene blue dye (as a compound representative of contaminants) were evaluated. Electrospun fiber morphologies without beads, branches, and ribbons were achieved by optimizing the electrospinning solutions. The thermal crosslinking between HPAM and CNCs was realized through esterification, rendering the product nanocomposite membranes insoluble in water. Electrospun fibers of approximately 220 nm in diameter comprised the 3D porous nanocomposite gels, with porosity greater than 50%. The porous nanocomposite gels displayed a rapid swelling rate and an efficient adsorption capacity in removing methylene blue at low concentrations from aqueous solutions.


Free fatty acids: a stimulus for mucin hypersecretion in cholesterol gallstone biles.
The concentration of free fatty acids, phosphatidylcholine and lysophosphatidylcholine, and the fatty acid composition as well as the levels of the mucins, analyzed by an improved GLC method, were examined in ten biles from patients with cholesterol gallstones (pathological biles) and in ten control biles. In pathological biles the amounts of free fatty acids and phosphatidylcholine, were significantly higher (8.99 +/- 1.09) vs. 2.75 +/- 0.62 micrograms/mg) and lower (6.62 +/- 0.71 vs. 21.91 +/- 3.86 micrograms/mg), respectively, than in control biles, indicating that a relationship exists between the two lipid fractions. Lysophosphatidylcholine concentrations remained unchanged in the two groups (1.02 +/- 0.55 micrograms/mg in pathological biles vs. 1.32 +/- 0.57 micrograms/mg in control biles). The increased levels of free fatty acids were directly correlated (r = 0.73, P less than 0.05) with biliary hypersecretion of mucus glycoproteins. Acetylglucosamine and acetylgalactosamine were significantly higher in pathological biles than in control biles (1.91 +/- 0.67 vs. 0.60 +/- 0.13 microgram/mg). The nucleating potency of the increased amounts of mucins, coupled with lowered levels of phosphatidylcholine, might play a very important role in stone formation and precipitation.


Anti-free-radical and neutrophil-modulating properties of the nitrovasodilator, nicorandil.
The nitrovasodilator, nicorandil, is a clinically effective antianginal agent. We tested whether nicorandil may also possess anti-free-radical characteristics, since the nicotinamide moiety of its molecular structure is a known hydroxyl radical scavenger. In vitro production of hydroxyl radicals by hypoxanthine plus xanthine oxidase in the presence of iron produced a marked degradation of deoxyribose. Nicorandil and the structural analogs, nicotinic acid and nicotinamide, produced significant inhibition of deoxyribose breakdown at concentrations equipotent to the classical hydroxyl radical scavenger, mannitol. Nicorandil also produced a concentration-dependent inhibition of superoxide anion production by canine neutrophils that were activated with either phorbol myristate acetate (PMA) or opsonized zymosan. This inhibition could not be mimicked by the analog, nicotinamide. While equimolar concentrations of nitroglycerin produced less inhibition of superoxide anion generation in opsonized zymosan-activated neutrophils than that observed with nicorandil, nitroglycerin did not alter free-radical production in PMA-stimulated neutrophils. Glyburide, the ATP-sensitive potassium-channel blocker, did not reverse the action of nicorandil on neutrophils. Thus, nicorandil is a uniquely different nitrovasodilator with anti-free-radical and neutrophil-modulating properties.


The association between frailty and anxiety: A systematic review.
Previous systematic reviews show a clear relationship between frailty and depression, however the association with anxiety is much less frequently explored. Previous single studies indicate evidence is mixed. We completed a systematic review and meta-analysis to identify the relationship between frailty and anxiety. We searched five electronic databases for observational studies in older people in community, care home and outpatient settings with any/no health conditions that measured the association between anxiety and frailty using validated measures. Studies were screened by one reviewer with 10% checked by a second reviewer. The Mixed Methods Appraisal Tool was used to assess study quality. We used meta-analysis to aggregate study findings, with subgroup analyses to explore heterogeneity. Out of 1272 references, a total of 20 cross-sectional and 1 longitudinal studies were eligible. Older adults with frailty were substantially more likely to display anxiety symptoms than robust populations, across both dichotomous and continuous data sets (n = 10, OR = 3.48, 95% CI: 2.08, 5.81, p < 0.0001, I2 = 94%; N = 5, SMD = 3.13, 95% CI: 1.06, 5.21, I2 = 98%). Similarly, pre-frail older adults were more likely to have anxiety symptoms than robust older adults but to a lesser extent (N = 6, OR = 1.95, 95% CI: 1.41, 2.71, I2 = 63%; N = 3, SMD = 1.70, 95% CI: 0.01, 3.38, I2 = 98%). There is a clear association between pre-frailty/frailty and anxiety in older adults. However, data are heterogeneous and primarily from cross-sectional studies so causality cannot be determined. Future research should evaluate the effectiveness of anxiety screening and treatments in frail older adults.


Exploitation of strong constitutive and stress-driven promoters from Acetobacter pasteurianus for improving acetic acid tolerance.
Acetobacter pasteurianus is an excellent cell factory for production of highly-strength acetic acid, and attracts an increasing attention in metabolic engineering. However, the available well-characterized constitutive and inducible promoters are rather limited to adjust metabolic fluxes in A. pasteurianus. In this study, we screened a panel of constitutive and acid stress-driven promoters based on time-series of RNA-seq data and characterized in A. pasteurianus and Escherichia coli. Nine constitutive promoters ranged in strength from 1.7-fold to 100-fold that of the well-known strong promoter Padh under non-acetic acid environment. Subsequently, an acetic acid-stable red fluorescent visual reporting system was established and applied to evaluate acid stress-driven promoter in A. pasteurianus during highly-acidic fermentation environment. PgroES was identified as acid stress-driven strong promoters, with expression outputs varied from 100% to 200% when acetic acid treatment. To assess their application potential, ultra-strong constitutive promoter Ptuf and acid stress-driven strong promoter PgroES were selected to overexpress acetyl-CoA synthase and greatly improved acetic acid tolerance. Notably, the acid stress-driven promoter displayed more favorable for regulating strain robustness against acid stress by overexpressing tolerance gene. In summary, this is the first well-characterized constitutive and acid stress-driven promoter library from A. pasteurianus, which could be used as a promising toolbox for metabolic engineering in acetic acid bacteria and other gram-negative bacteria.