Effects of a hyperbaric environment on respiratory and monoamine oxidase activities.
The effects of a prolonged hyperbaric environment (21 ATA He-O2, 200 +/- 30 mm Hg O2, 32.5 +/- 1 degrees C) were investigated on the respiratory activity of rat liver homogenates and the activity of monoamine oxidase in isolated rat-liver preparations. Exposure to a hyperbaric environment for 84 days caused selective in vitro inhibition of nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, D-isocitrate, and alpha-ketoglutarate by rat-liver homogenates. The addition of NAD to the reaction mixture decreased the degree of such an inhibition. No effects on the in vitro activity of liver monoamine oxidase and its inhibition by pheniprazine were observed during exposure of animals to a prolonged high-pressure environment.


Privacy-preserving federated learning for scalable and high data quality computational-intelligence-as-a-service in Society 5.0.
Training supervised machine learning models like deep learning requires high-quality labelled datasets that contain enough samples from various categories and specific cases. The Data as a Service (DaaS) can provide this high-quality data for training efficient machine learning models. However, the issue of privacy can minimize the participation of the data owners in DaaS provision. In this paper, a blockchain-based decentralized federated learning framework for secure, scalable, and privacy-preserving computational intelligence, called Decentralized Computational Intelligence as a Service (DCIaaS), is proposed. The proposed framework is able to improve data quality, computational intelligence quality, data equality, and computational intelligence equality for complex machine learning tasks. The proposed framework uses the blockchain network for secure decentralized transfer and sharing of data and machine learning models on the cloud. As a case study for multimedia applications, the performance of DCIaaS framework for biomedical image classification and hazardous litter management is analysed. Experimental results show an increase in the accuracy of the models trained using the proposed framework compared to decentralized training. The proposed framework addresses the issue of privacy-preserving in DaaS using the distributed ledger technology and acts as a platform for crowdsourcing the training process of machine learning models.


Orthopaedic Trauma Never Sleeps: Resource Allocation Even During a Non-trauma Crisis.
This study aimed to describe hospital resource utilization of an orthopaedic trauma service and the injury epidemiology during the 2019-2020 coronavirus pandemic to help plan future non-trauma crises. A retrospective chart review was performed on adult patients > 18 years of age who presented to our Level I Trauma Center for musculoskeletal trauma from March 30, 2020 to May 8, 2020 (stay-at-home order) and from March 30, 2019 to May 8, 2019 (comparison group). There were 182 patient encounters and 274 fractures in the 2020 stay-at-home period, and there were 210 patient encounters and 337 fractures in the 2019 control group. There was no statistical difference found comparing the proportion of patient encounters in the stay-at-home period to the control period (p > 0.05). The similar volume of consultations and surgeries justifies maintenance of standard resource allocation. (Journal of Surgical Orthopaedic Advances 32(2):102-106, 2023).


Use of prescription drug samples in the US and implications for pharmacoepidemiologic research: a systematic search of the literature.
Free drug samples are not captured in the pharmacy claims databases used in many pharmacoepidemiologic studies, which could lead to misclassification of drug exposure status and thus bias study results. We systematically searched the literature in PubMed/MEDLINE, Embase, and Scopus from database inception to August 2020 for studies assessing the magnitude of exposure misclassification in pharmacy claims data associated with uncaptured drug sample utilization. Our review identified five US-based studies with substantially different characteristics, contexts, methods, and results. Taken together, these studies suggest that the risk of sample-related bias may be higher for (1) studies of newly approved, patented brand-only drugs in specific classes and contexts; (2) studies of populations where sample use is common and the unexposed cohort is small; and (3) studies where the outcomes of interest are expected to be early-onset or acute, with non-constant hazards. In light of declining overall trends in sample use, future research on sample-related exposure misclassification should focus on delineating bias across those modern contexts where sample use remains high and optimizing bias quantification methods to create a more standardized approach. Additionally, further assessment is warranted for other sources of misclassified exposure status in claims-based pharmacoepidemiology research.


Calibration of the isomer shift for the 77.34 keV transition in 197Au using the full-potential linearized augmented plane-wave method.
The isomer shift calibration constant has been calculated for the 77.34 keV Mossbauer transition connecting the ground state of the (197)Au nucleus with the first excited state of this nucleus. The full-potential linearized augmented plane-wave method was used in the fully relativistic approach, albeit without taking into account the spin-orbit coupling. The final assignment of the calibration constant was based on calculations performed for AuCN, AuCl(3), AuBr(3), KAuCl(4), KAuBr(4), and metallic gold. It is found that the calibration constant takes on the following value alpha = +0.0665(4) mm s(-1) a.u.(3). The error quoted is due to the linear regression fit, and the real error might be as large as 10%. The spectroscopic electric quadrupole moment for the ground state of the (197)Au nucleus was calculated as the by-product. It was found that this moment equals Q(g) = +0.566(1)b in fair agreement with the accepted value based on the muonic hyperfine spectroscopy results. The error quoted is again due to the linear regression fit and the real error might be as large as 10%. The final assignment of the value for the quadrupole moment is based on the calculations for the following compounds: AuCl, AuBr, AuI, AuCN, and AuMn(2). Results for the magnetically ordered Au(2)Mn were applied to determine the sign of the quadrupole moment.


[Genetic modifier loci of transplanted SP2/0 tumors in mice].
Our previous study found that BALB/c mice are highly susceptible to transplanted SP2/0 tumors, whereas C57BL/6J mice are barely susceptible. This study was to detect genetic modifier loci that would influence the size of transplanted SP2/0 tumors using these two inbred mouse strains and their F2 progenies. A total of 5x106 SP2/0 cells were inoculated subcutaneously in the left hide legs of 208 F2 mice derived from BALB/c and C57BL/6J strains. At the 17th day since inoculation, all mice were killed, the number and weight of transplanted tumors were recorded. A whole genomic scan using 85 microsatellite markers covering all chromosomes of the mouse, and composite interval mapping analysis were conducted in 208 F2 mice. Eight loci, with the percent of the total variance explanation of > or = 10% and P value of < or = 0.01, were found responsible for tumor formation. They were mapped on Chr1 (D1Mit113, 55cM and D1Mit407, 52 cM), Chr4 (D4Mit226, 41cM), Chr9 (D9Mit302, 55cM), Chr10 (D10Mit264, 42cM), Chr11 (D11Mit115, 35cM), Chr14 (D14Mit125, 45cM), and Chr18 (D18Mit123, 31cM). Multiple genetic variants affect individual susceptibility to transplanted SP2/0 tumors in mice. Identification of the target loci may be helpful in conformation of the haplotype and understanding of the genes responsible for tumor susceptibility or resistance.


Control of phosphate appetite in young rats.
In the present study, we investigated whether a diet deficient in inorganic phosphate (Pi) stimulates an ingestive behavior to seek sources of Pi. Male Wistar rats were placed in individual cages with unrestricted access to tap water and a low (LPD, 0.02% Pi) or normal (NPD, 0.6% Pi) Pi diet for 6 days. On day 7, LDP rats were given unlimited access to a solution of 25 mM potassium phosphate water (Pi-water) for 9 additional days. Rats fed LPD consumed 70-100% more Pi-water then those fed NPD. The increase in Pi-water intake resulted in a marked rise in the growth rate of rats fed LPD during day 9. A similar intake of Pi was induced after only 2 days of LPD and was associated with significant reductions in both plasma and cerebrospinal fluid (CSF) levels of Pi; these levels remained low throughout Pi restriction, despite a significant intake of Pi-water. Replenishment with a high-Pi diet rapidly quenched the appetite for Pi-water and was associated with restoration of both plasma and CSF Pi levels. These findings suggest that an appetite for Pi can be induced in rats, perhaps through lowered plasma and CSF Pi levels.


Analysis of the Effectiveness of Music Therapy on Mental Health of College Students.
Music therapy is a relatively mature marginal subject at present, and it is also a relatively common treatment method. This kind of treatment can better help college students get rid of bad psychology and guide their psychology to develop in a healthy direction. Mental health is one of the important indicators to measure the comprehensiveness of human quality and plays an important role in the sustainable development of human beings. Music therapy plays a very important role in college students' mental health education. As a marginal subject, music therapy combines music, medicine, and psychology, which is beneficial to alleviate students' bad emotions and psychological problems, and helps college students form a sound personality. Using music therapy can let college students vent their emotions in a suitable environment and atmosphere and then guide them correctly. This paper introduces the effectiveness of music therapy in college students' mental health education and then puts forward important measures to promote the implementation of music therapy in college students' mental health education.


How does the VPD response of isohydric and anisohydric plants depend on leaf surface particles?
Atmospheric vapour pressure deficit (VPD) is the driving force for plant transpiration. Plants have different strategies to respond to this 'atmospheric drought'. Deposited aerosols on leaf surfaces can interact with plant water relations and may influence VPD response. We studied transpiration and water use efficiency of pine, beech and sunflower by measuring sap flow, gas exchange and carbon isotopes, thereby addressing different time scales of plant/atmosphere interaction. Plants were grown (i) outdoors under rainfall exclusion (OD) and in ventilated greenhouses with (ii) ambient air (AA) or (iii) filtered air (FA), the latter containing <1% ambient aerosol concentrations. In addition, some AA plants were sprayed once with 25 mM salt solution of (NH4 )2 SO4 or NaNO3 . Carbon isotope values (δ(13) C) became more negative in the presence of more particles; more negative for AA compared to FA sunflower and more negative for OD Scots pine compared to other growth environments. FA beech had less negative δ(13) C than AA, OD and NaNO3 -treated beech. Anisohydric beech showed linearly increasing sap flow with increasing VPD. The slopes doubled for (NH4 )2 SO4 - and tripled for NaNO3 -sprayed beech compared to control seedlings, indicating decreased ability to resist atmospheric demand. In contrast, isohydric pine showed constant transpiration rates with increasing VPD, independent of growth environment and spray, likely caused by decreasing gs with increasing VPD. Generally, NaNO3 spray had stronger effects on water relations than (NH4 )2 SO4 spray. The results strongly support the role of leaf surface particles as an environmental factor affecting plant water use. Hygroscopic and chaotropic properties of leaf surface particles determine their ability to form wicks across stomata. Such wicks enhance unproductive water loss of anisohydric plant species and decrease CO2 uptake of isohydric plants. They become more relevant with increasing number of fine particles and increasing VPD and are thus related to air pollution and climate change. Wicks cause a deviation from the analogy between CO2 and water pathways through stomata, bringing some principal assumptions of gas exchange theory into question.


Bell-bottom aortoiliac endografts: an alternative that preserves pelvic blood flow.
Dilated common iliac arteries that complicate aortic aneurysm stent grafting usually have been managed with endograft extension across the iliac artery bifurcation with internal iliac artery (IIA) occlusion. We studied 25 patients with significant common iliac artery (CIA) dilation treated with two methods: endograft extension across the iliac bifurcation or a new approach with a flared cuff within the CIA that preserves the IIA. Of 86 patients with abdominal aortic aneurysm (AAA) who underwent bifurcated endovascular stent grafting (ESG), 25 (29.1%) had at least one dilated CIA. Two treatment groups had different methods of management of iliac artery dilation. Group 1 underwent ESG with straight extension across the iliac bifurcation and IIA coil embolization before the ESG procedure (n = 2) or simultaneously with ESG (n = 8). Group 2 underwent ESG with flared distal cuff (AneuRx, Medtronic AVE, Santa Rosa, Calif) contained within the CIA, the so-called "bell-bottom" procedure, thus preserving the IIA (n = 15). Iliac artery dimensions, operating room time, fluoroscopy time, and postoperative complications were prospectively gathered. Two women and 23 men had mean diameters of AAA of 56.6 mm (range, 38 to 98 mm) and of CIA of 21.4 mm (range, 15 to 48 mm). The diameters of CIA treated with device extension into external iliac artery after IIA coil embolization in group 1 and with the bell-bottom procedure in group 2 were not different (mean CIA diameter, 19.9 mm; range, 15 to 26 mm; and mean, 19.1 mm; range, 15 to 24 mm; respectively). However, significantly lower operating room and catheter procedure times were found in group 2 compared with group 1 (137 versus 192 minutes; 58 versus 106 minutes; P =.02 and.02, respectively). No periprocedural type I endoleaks were found in either group. Nine patients in group 2 also had a second contralateral CIA aneurysm, and five patients (mean CIA diameter, 33.0 mm; range, 22 to 48 mm) underwent treatment with extension across the iliac artery bifurcation and IIA occlusion. Use of the bell-bottom procedure on the other side allowed preservation of one IIA. Four cases (mean diameter, 19.3 mm) also underwent contralateral bell-bottom procedure. Two of these group 2 patients had complications, with severe buttock claudication in one and distal embolism necessitating limb salvage bypass after preoperative coil embolization of the IIA in another. Significant CIA ectasia or small aneurysm is often associated with AAA. In such cases, the bell-bottom procedure that preserves IIA circulation is a new alternative to the common practice of placement of endograft extensions across the iliac artery bifurcation in patients with at least one CIA diameter of less than 26 mm. Additional benefits include reduced total procedure time. Early technical success appears to justify continued use. However, long-term evaluation is necessary to determine durability because the risk of rupture as the result of potential expansion of the excluded iliac artery or late failure is unknown.


Physio-biochemical responses and expressional profiling analysis of drought tolerant genes in new promising rice genotype.
Rice cultivation in Egypt is limited by the scarcity of water resources. The main strategy of rice breeders to overcome this problem is to develop new high-yielding varieties that are tolerant to drought stress. In this study, an drought-tolerant (IR60080-46A) variety was crossed with commercial Egyptian varieties using the back-cross method and marker-assisted selection (MAS) approach. The advanced lines of these crosses were selected under drought stress conditions. The best-performing candidate line, RBL-112, and its parental genotypes, were evaluated under drought stress and control conditions. The RBL-112 line showed superior its root system, which in turn produced higher grain yield under drought-stress conditions than its parental and check genotypes. Furthermore, physiological and biochemical studies showed that the RBL-112 line maintained higher relative water content (RWC), maximum quantum efficiency of photosystem II (Fv/Fm) values, proline content, superoxide dismutase (SOD) activity, and lower malondialdehyde (MDA) content compared to its parents and the check. The functional expression profiles of 22 drought tolerance-related genes were studied, out of which the genes OsAHL1, OsLEA3, OsCATA, OsP5CS, OsSNAC1, Os1g64660, OsRab21, OsAPX2, OsDREB2A, OsSKIPa, and OsLG3 were strongly induced in the newly developed RBL-112 line under drought-stress conditions. It could be concluded that the new line has a higher capacity to modulate physiological activities and expression levels of several drought-induced genes to withstand drought stress with high yielding ability. This finding suggests that the RBL-112 line presents a promising new addition to enable sustainable rice cultivation under water-limited conditions, and confirms the efficiency of the approach implemented in the current study.


Implementation of 'One Health' approach in Kerala state, India - A systematic review.
With humans, animals and the environment being as interconnected as they are, the science describing their interactions needs to cut across disciplinary boundaries. Systems research at the interface between the three goes by several names, such as 'Eco-Health' and 'Planetary Health', each with a varied focus, but the concept of 'One Health' (OH) has stood out as the most popular one. COVID-19 has reiterated the importance of OH in response to health challenges. This review aimed to assess the OH approach integration and implementation level in Kerala state, India, in the context of emerging zoonotic diseases. A systematic literature review was conducted by searching for relevant articles with specific keywords across six electronic databases. This involved screening the initial hits for titles and abstracts, then systematic sorting to identify the ones that met the criteria, followed by more thorough scrutiny to finally shortlist the six studies to be included in the review. We found that OH in Kerala has made good progress, as evident from a few recent examples, but has a long way to go with significant challenges. In line with the study's aim, identifying and analysing what is already done, what is missing and what needs to be done can have wider implications for future OH implementation. Relevant threats and opportunities were identified, with lessons for Kerala and India and broader applications.


[A rating scale and therapeutic strategy in dysphagia in patients with brain stem damage].
Dysphagia appears in 15-17% of cases after removal of tumors of the posterior cranial fossa (PCF), which is one of the most life-threatening postoperative complications due to a risk of acute airway patency impairment, possible aspiration, bronchopulmonary infectious complications. This makes prognosis workse and complicates a patient's rehabilitation. Based on the results of fibrolaryngotracheoscopic study and treatment of 1653 patients operated on for PCF tumors, the authors have developed a scale for rating the severity of bulbar disorders. The proposed scale promotes decision making on the expediency of performing tracheostomy and on the necessity of evaluating the efficiency of performed therapy (trends in bulbar disorders) and predicting the course of a postoperative period.


Estimation of hominoid ancestral population sizes under bayesian coalescent models incorporating mutation rate variation and sequencing errors.
Estimation of population parameters for the common ancestors of humans and the great apes is important in understanding our evolutionary history. In particular, inference of population size for the human-chimpanzee common ancestor may shed light on the process by which the 2 species separated and on whether the human population experienced a severe size reduction in its early evolutionary history. In this study, the Bayesian method of ancestral inference of Rannala and Yang (2003. Bayes estimation of species divergence times and ancestral population sizes using DNA sequences from multiple loci. Genetics. 164:1645-1656) was extended to accommodate variable mutation rates among loci and random species-specific sequencing errors. The model was applied to analyze a genome-wide data set of approximately 15,000 neutral loci (7.4 Mb) aligned for human, chimpanzee, gorilla, orangutan, and macaque. We obtained robust and precise estimates for effective population sizes along the hominoid lineage extending back approximately 30 Myr to the cercopithecoid divergence. The results showed that ancestral populations were 5-10 times larger than modern humans along the entire hominoid lineage. The estimates were robust to the priors used and to model assumptions about recombination. The unusually low X chromosome divergence between human and chimpanzee could not be explained by variation in the male mutation bias or by current models of hybridization and introgression. Instead, our parameter estimates were consistent with a simple instantaneous process for human-chimpanzee speciation but showed a major reduction in X chromosome effective population size peculiar to the human-chimpanzee common ancestor, possibly due to selective sweeps on the X prior to separation of the 2 species.


Toluene can perturb the neuronal voltage-dependent Ca2+ channels involved in the middle-ear reflex.
Numerous laboratory-based data have shown the ability of toluene (Tol) to exacerbate noise-induced hearing loss. However, the mechanism responsible for the synergistic effects of a coexposure to noise and Tol has not yet been completely elucidated. Recent investigations in rats have focused on quantifying the anticholinergic effects of certain aromatic solvents and have demonstrated that these solvents can cancel the protective role played by the middle-ear reflex (MER). Voltage-dependent Ca(2+) channels (VDCCs) regulate acetylcholine release in the central synaptic network and control muscular excitation/contraction processes as well. In order to identify the prevailing action of Tol in the central or peripheral compartment of the MER arc, two VDCC antagonists were injected into the common carotid trunk: omega-conotoxin MVIIC, which blocks only the neuronal N- and P/Q-type Ca(2+) channels, or verapamil, which inhibits the muscular L-type Ca(2+) channels. Rats were also implanted with an electrode on the round window membrane to measure the cochlear microphonic potential (CMP) elicited with a band noise centered at 4 kHz and emitted at 85 dB sound pressure level. The variations in CMP recorded during the test compound injection showed that Tol has similar effects to those induced by omega-conotoxin, the neuronal VDCC blocker. The response obtained with the verapamil injection was broader than those obtained with Tol or conotoxin. This investigation therefore revealed that Tol can mimic the effects of VDCC blockers. The antagonist effects of Tol would be closer to neuronal than to muscular blockers and would be presumably located at the level of the integrator centers of the reflex.


Serratia marcescens.
Serratia marcescens is now recognized as a serious pathogen and of particular importance in nosocomial infections. Both hand-to-hand and point-source transmission can result in outbreaks. The organism is easily grown and identified in the microbiology laboratory. Treatment may be difficult due to plasmid-mediated resistance. Typing systems are available and can be useful for epidemiologic studies.


[A case of Ellis-van Creveld syndrome with partial atrioventricular septal defect and double orifice mitral valve].
Ellis-van Creveld Syndrome (ECS) is characterized by chondrodysplasia, ectodermal dysplasia, polydactyly, and congenital cardiac defects. As congenital cardiac defects, single atrium and endocardial cusion defect are frequent in literatures. We described a case, a 68-year-old woman, presenting with ECS with partial atrioventricular septal defect and double orifice mitral valve. The partial atrioventricular septal defect was repaired by closure with a Dacron patch. The accessory orifice was located at the anterior cusp of the mitral valve, which was left, untouched, because no regurgitation had been detected preoperatively. Her postoperative course was uneventful, and the patient was discharged on 25th postoperative day.


Exploring the Landscape of Diazabicyclooctane (DBO) Inhibition: Avibactam Inactivation of PER-2 β-Lactamase.
PER β-lactamases are an emerging family of extended-spectrum β-lactamases (ESBL) found in Gram-negative bacteria. PER β-lactamases are unique among class A enzymes as they possess an inverted omega (Ω) loop and extended B3 β-strand. These singular structural features are hypothesized to contribute to their hydrolytic profile against oxyimino-cephalosporins (e.g., cefotaxime and ceftazidime). Here, we tested the ability of avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor to inactivate PER-2. Interestingly, the PER-2 inhibition constants (i.e., k2/K = 2 × 103 ± 0.1 × 103 M-1 s-1, where k2 is the rate constant for acylation (carbamylation) and K is the equilibrium constant) that were obtained when AVI was tested were reminiscent of values observed testing the inhibition by AVI of class C and D β-lactamases (i.e., k2/K range of ≈103 M-1 s-1) and not class A β-lactamases (i.e., k2/K range, 104 to 105 M-1 s-1). Once AVI was bound, a stable complex with PER-2 was observed via mass spectrometry (e.g., 31,389 ± 3 atomic mass units [amu] → 31,604 ± 3 amu for 24 h). Molecular modeling of PER-2 with AVI showed that the carbonyl of AVI was located in the oxyanion hole of the β-lactamase and that the sulfate of AVI formed interactions with the β-lactam carboxylate binding site of the PER-2 β-lactamase (R220 and T237). However, hydrophobic patches near the PER-2 active site (by Ser70 and B3-B4 β-strands) were observed and may affect the binding of necessary catalytic water molecules, thus slowing acylation (k2/K) of AVI onto PER-2. Similar electrostatics and hydrophobicity of the active site were also observed between OXA-48 and PER-2, while CTX-M-15 was more hydrophilic. To demonstrate the ability of AVI to overcome the enhanced cephalosporinase activity of PER-2 β-lactamase, we tested different β-lactam-AVI combinations. By lowering MICs to ≤2 mg/liter, the ceftaroline-AVI combination could represent a favorable therapeutic option against Enterobacteriaceae expressing blaPER-2 Our studies define the inactivation of the PER-2 ESBL by AVI and suggest that the biophysical properties of the active site contribute to determining the efficiency of inactivation.


The critical factors for COVID-19 vaccination uptake are perceived vaccine effectiveness and the desire to protect others.
The proportion of the population vaccinated in Israel against COVID-19 in 2021 was significantly higher than that of the annual uptake rates of the influenza vaccine over time. Understanding the reasons behind the high vaccination rate may facilitate maintaining these rates if annual COVID-19 vaccination is required. Using a mixed-methods design, we characterized the individuals who were vaccinated and studied their attitudes toward vaccines and motivators for the COVID-19 vaccine. The first part was a cross-sectional study of adults aged 65 and over who were vaccinated against COVID-19. We stratified them according to their annual influenza vaccination patterns, and compared variables such as age, gender, health status, and timing of COVID-19 vaccination. The second part consisted of a questionnaire administered to a subsample of the above population, inquiring about vaccine hesitancy, motivators for vaccination, and intention to be vaccinated in the future. We found that motivating factors for COVID-19 vaccination are similar between those who regularly vaccinate against influenza and those who don't. Internal motivators such as perceived vaccine effectiveness and the desire to protect others were stronger than external rewards or sanctions. High adherence to annual influenza vaccine recommendations was associated with earlier COVID-19 vaccine uptake. Respondents with lower adherence to influenza vaccines were more likely to demonstrate higher levels of vaccine hesitancy. These factors should be addressed in future vaccination campaigns.


Repressive coping style and its relation to psychosocial distress in males with erectile dysfunction.
There is evidence that repressive coping adversely affects medical conditions such as coronary heart disease, hypertension, and bronchial asthma. Erectile dysfunction (ED) is known to have a severe and lasting negative impact on health, quality of life, and partnership. Although ED may be eminently threatening for the self-image of affected men, a repressive coping style and its consequences for their mental health and partnership has not yet been investigated. Based on the presumption that the male self-image is threatened by ED, we expected men with repressive coping strategies-although reporting the same degree of impairments regarding their sexual function-to describe themselves as more satisfied with: (i) their sexual relationship, to report (ii) a better quality of their partnership; and (iii) less distress (depression and physical complaints) as compared with those who do not use such strategies. Fifty-nine patients with ED from the outpatient unit of the Clinic of Urology, Pediatric Urology and Andrology of the University of Giessen were examined using standardized German versions of international questionnaires. Coping style was determined using a combination of the State Trait Anxiety Inventory (STAI) and the Marlowe Crown Social Desirability Scale (SDS-CM) measuring defensiveness. Questionnaires measuring anxiety (STAI), depression (Center for Epidemiological Studies Depression Scale), social desirability (SDS-CM), quality of partnership (Partnership Questionnaire), and physical complaints (Complaint List) were administered. Repressors did not differ from nonrepressors with regard to their self-reported sexual function (International Index of Erectile Function). However, they described themselves as less distressed (depression, physical complaints) and rated the quality of their partnership as higher. Repressors tend to report their complaints in a manner that protects their self-worth. Clinicians therefore might have difficulties deciding whether and which treatment is necessary. Additional clinical information (e.g., interview together with the female partner) or questionnaires might prove useful sources of information on patients' coping style.


Interferon α-induced sarcoidosis to a patient with polycythemia vera.
Treatment with interferon (IFN) can precipitate a variety of inflammatory conditions, including sarcoidosis. Although many other systems can be affected, the clinical picture in this case mostly includes cutaneous and pulmonary symptoms. The prognosis is better than the idiopathic form of the disease, and the most effective treatment is considered the discontinuation of antivirus therapy alone or in combination with corticosteroid administration. The authors present the case of a 36-year-old man who developed sarcoidosis stage I after 2 years of IFNα therapy for polycythemia vera.


Cell processing engineering for ex-vivo expansion of hematopoietic cells.
The cell processing engineering for ex vivo expansion of hematopoietic cells is reviewed. All hematopoietic cells of different lineages and/or at various stages of differentiation are derived from the same precursor, pluripotent hematopoietic stem cells. Bone marrow stromal cells promote and regulate the self-renewal, commitment, differentiation, and proliferation of stem cells and progenitors through their secreted extracellular matrices and cytokine environment in the hematopoietic microenvironment. Although stroma-mediated hematopoiesis has been studied in vitro using the Dexter culture system in tissue culture flasks, hematopoiesis in the Dexter culture system is almost limited to a granulocyte lineage and the system could not expand primitive cells. The addition of large amounts of cytokines to the culture of hematopoietic cells enabled their expansion, but is too expensive. Some clonal stromal cell lines have been established from the Dexter culture of murine bone marrow cells in order to simplify and stimulate the ex vivo expansion of hematopoietic cells. In order to solve the problem regarding the usage of exogeneic stromal cell lines, a novel membrane-separated coculture system, in which stromal cells adhere onto the lower surface of a porous membrane and hematopoietic cells are incubated on the upper surface of the membrane, was proposed. In order to mimic the contact between stromal and hematopoietic cells in vivo in the bone marrow, several types of three-dimensional (3-D) culture of hematopoietic cells were developed. The 3-D coculture of hematopoietic cells with spatial development of stromal cells in nonwoven fabrics enabled the expansion of progenitors without cytokine addition. Progenitors in cord blood mononucleated cells were also successfully expanded without the addition in the 3-D coculture with primary human bone marrow stromal cells in 3-D. Heparin addition to the 3-D coculture and coating the nonwoven fabrics with N-(O-beta-(6-O-sulfogalactopyranosyl)-6-oxyhexyl)-3,5-bis(dodecyloxy)-benzamide further increased the number of progenitors.


Variations in active transport behavior among different neighborhoods and across adult lifestages.
Built environment characteristics are closely related to transport behavior, but observed variations could be due to residents own choice of neighborhood called residential self-selection. The aim of this study was to investigate differences in neighborhood walkability and residential self-selection across life stages in relation to active transport behavior. The IPEN walkability index, which consists of four built environment characteristics, was used to define 16 high and low walkable neighborhoods in Aarhus, Denmark (250.000 inhabitants). Transport behavior was assessed using the IPAQ questionnaire. Life stages were categorized in three groups according to age and parental status. A factor analysis was conducted to investigate patterns of self-selection. Multivariable logistic regression analyses were carried out to evaluate the association between walkability and transport behavior i.e. walking, cycling and motorized transport adjusted for residential self-selection and life stages. A total of 642 adults aged 20-65 years completed the questionnaire. The highest rated self-selection preference across all groups was a safe and secure neighborhood followed by getting around easily on foot and by bicycle. Three self-selection factors were detected, and varied across the life stages. In the multivariable models high neighborhood walkability was associated with less motorized transport (OR 0.33 95%CI 0.18-0.58), more walking (OR 1.65 95%CI 1.03-2.65) and cycling (OR 1.50 95% CI 1.01-2.23). Self-selection and life stage were also associated with transport behavior, and attenuated the association with walkability. This study supports the hypothesis that some variation in transport behavior can be explained by life stages and self-selection, but the association between living in a more walkable neighborhood and active transport is still significant after adjusting for these factors. Life stage significantly moderated the association between neighborhood walkability and cycling for transport, and household income significantly moderated the association between neighborhood walkability and walking for transport. Getting around easily by bicycle and on foot was the highest rated self-selection factor second only to perceived neighborhood safety.


Discovery of MicroRNAs and Their Target Genes Related to Drought in Paulownia "Yuza 1" by High-Throughput Sequencing.
Understanding the role of miRNAs in regulating the molecular mechanisms responsive to drought stress was studied in Paulownia "yuza 1." Two small RNA libraries and two degradome libraries were, respectively, constructed and sequenced in order to detect miRNAs and their target genes associated with drought stress. A total of 107 miRNAs and 42 putative target genes were identified in this study. Among them, 77 miRNAs were differentially expressed between drought-treated Paulownia "yuza 1" and the control (60 downregulated and 17 upregulated). The predicted target genes were annotated using the GO, KEGG, and Nr databases. According to the functional classification of the target genes, Paulownia "yuza 1" may respond to drought stress via plant hormone signal transduction, photosynthesis, and osmotic adjustment. Furthermore, the expression levels of seven miRNAs (ptf-miR157b, ptf-miR159b, ptf-miR398a, ptf-miR9726a, ptf-M2153, ptf-M2218, and ptf-M24a) and their corresponding target genes were validated by quantitative real-time PCR. The results provide relevant information for understanding the molecular mechanism of Paulownia resistance to drought and reference data for researching drought resistance of other trees.


Improving nitrogen source utilization from defatted soybean meal for nisin production by enhancing proteolytic function of Lactococcus lactis F44.
Nisin, one kind of natural antimicrobial peptide, is produced by certain Lactococcus lactis strains, which generally require expensive high-quality nitrogen sources due to limited ability of amino acids biosynthesis. Here we use defatted soybean meal (DSM) as sole nitrogen source to support L. lactis growth and nisin production. DSM medium composition and fermentation conditions were optimized using the methods of Plackett-Burman design and central composite design. The highest nisin production of 3879.58 IU/ml was obtained in DSM medium, which was 21.3% higher than that of commercial medium. To further increase the utilization ability of nitrogen sources, we enhanced the proteolytic function in L. lactis through rationally expressing the related enzymes, which were selected according to the compositions of amino acids and molecular weight of peptides in DSM medium. Significantly, an artificial proteolytic system consisting of a heterologous protease (NprB), an oligopeptides transporter subunit (OppA) and two peptidases (PepF and PepM) was introduced into L.lactis. The constructed strain BAFM was capable of achieving efficient biomass accumulation and nisin yield with 30% decreased amount of DSM hydrolysates, which further reduced the cost of nisin production. The strategy described here offers opportunities for low-cost L. lactis fermentation and large-scale nisin production in industry.


Effects of conditioned food aversions on nutritional behavior in humans.
Conditioned food aversion (CFA) and taste aversion (CTA) are widely occurring phenomena mediating rejection of solids or liquids, the ingestion of which has induced the onset of post-ingestional malaise. It is a powerful and durable imprint learning that may influence food choice and intake in all animals, including humans. For ethical reasons, CTA has been extensively investigated in a wide variety of laboratory animal's species but only incidentally in humans. Nevertheless, convincing evidence has been provided that CFA and CTA learning are possible in a wide range of human subjects. The results in humans may have some limitations in accuracy since data are sparse, sometimes indirect, and poorly controlled. There is only limited information on the extent of CFA in the elderly since most studies have employed questionnaire and/or interview methods on young people (i.e. college students). The present review evaluates the literature derived both from laboratory animals and humans. In the first instance, the salient features of food and taste aversion learning and the neural mechanisms involved in this learning behavior will be examined. Then, the problems encountered when trying to assess the role of learned food and taste aversions in the nutritional status of healthy as well as sick young or elderly people will be considered. In particular, the importance of CFA on the nutritional status of cancer patients and treatment of alcoholism will be examined. It is concluded that the data are compelling enough to warrant further research and, some indications and recommendations are suggested.


Antiadhesion agents against Gram-positive pathogens.
A fundamental step of Gram-positive pathogenesis is the bacterial adhesion to the host tissue involving interaction between bacterial surface molecules and host ligands. This review is focused on antivirulence compounds that target Gram-positive adhesins and on their potential development as therapeutic agents alternative or complementary to conventional antibiotics in the contrast of pathogens. In particular, compounds that target the sortase A, wall theicoic acid inhibitors, carbohydrates able to bind bacterial proteins and proteins capable of influencing the bacterial adhesion, were described. We further discuss the advantages and disadvantages of this strategy in the development of novel antimicrobials and the future perspective of this research field still at its first steps.


Apoptosis inhibition of Atlantic salmon (Salmo salar) peritoneal macrophages by Piscirickettsia salmonis.
To improve the understanding of the piscirickettsiosis pathogenesis, the in vivo apoptosis modulation of peritoneal macrophages and lymphocytes was studied in juvenile Salmo salar intraperitoneally injected with Piscirickettsia salmonis. Five fish were sampled at post-exposure days 1, 5, 8 (preclinical), 20 (clinical) and 40 (post-clinical period of the disease), and the leucocytes of their coelomic washings were analysed by flow cytometry (using the JC-1 cationic dye), TUNEL and cytology to detect apoptotic cells. A selective and temporal pattern of apoptosis modulation by P. salmonis infection was observed. Apoptosis in lymphocytes was not affected, whereas it was inhibited in macrophages but only during the preclinical stage of the induced piscirickettsiosis. Hence, it is postulated that P. salmonis inhibits macrophage apoptosis at the beginning of the disease development to survive, multiply and probably be transported inside these phagocytes; once this process is complete, macrophage apoptosis is no longer inhibited, thus facilitating the exit of the bacteria from the infected cells for continuing their life cycle.


Risk assessment of exposure to lead in tap water among residents of Seri Kembangan, Selangor state, Malaysia.
A cross sectional study was conducted to estimate risk of exposure to lead via tap water ingestion pathway for the population of Seri Kembangan (SK). By using purposive sampling method, 100 respondents who fulfilled the inclusive criteria were selected from different housing areas of SK based on geographical population distribution. Residents with filtration systems installed were excluded from the study. Questionnaires were administered to determine water consumption-related information and demographics. Two water samples (first-flushed and fully-flushed samples) were collected from kitchen tap of each household using HDPE bottles. A total of 200 water samples were collected and lead concentrations were determined using a Graphite Furnace Atomic Absorption Spectrophotometer (GFAAS). Mean lead concentration in first-flushed samples was 3.041± SD 6.967µg/L and 1.064± SD 1.103µg/L for fully-flushed samples. Of the first-flushed samples, four (4) had exceeded the National Drinking Water Quality Standard (NDWQS) lead limit value of 10µg/L while none of the fully-flushed samples had lead concentration exceeded the limit. There was a significant difference between first-flushed samples and fully-flushed samples and flushing had elicited a significant change in lead concentration in the water (Z = -5.880, p<0.05). It was also found that lead concentration in both first-flushed and fully flushed samples was not significantly different across nine (9) areas of Seri Kembangan (p>0.05). Serdang Jaya was found to have the highest lead concentration in first-flushed water (mean= 10.44± SD 17.83µg/L) while Taman Universiti Indah had the highest lead concentration in fully-flushed water (mean=1.45± SD 1.83µg/L). Exposure assessment found that the mean chronic daily intake (CDI) was 0.028± SD 0.034µgday-1kg-1. None of the hazard quotient (HQ) value was found to be greater than 1. The overall quality of water supply in SK was satisfactory because most of the parameters tested in this study were within the range of permissible limit and only a few samples had exceeded the standard values for lead and pH. Non-carcinogenic risk attributed to ingestion of lead in SK tap water was found to be negligible.


Risk factors of osteonecrosis of the jaw after tooth extraction in osteoporotic patients on oral bisphosphonates.
The aim of this study was to investigate the incidence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after tooth extraction in patients with osteoporosis on oral bisphosphonates in Korea and to evaluate local factors affecting the development of BRONJ. The clinical records of 320 patients who underwent dental extraction while receiving oral bisphosphonates were reviewed. All patients had a healing period of more than 6 months following the extractions. Each patient's clinical record was used to assess the incidence of BRONJ; if BRONJ occurred, a further radiographic investigation was carried out to obtain a more definitive diagnosis. Various local factors including age, gender, extraction site, drug type, duration of administration, and C-terminal telopeptide (CTx) level were retrieved from the patients' clinical records for evaluating their effect on the incidence of BRONJ. Among the 320 osteoporotic patients who underwent tooth extraction, 11 developed BRONJ, reflecting an incidence rate of 3.44%. Out of the local factors that may affect the incidence of BRONJ, gender, drug type, and CTx level showed no statistically significant effects, while statistically significant associations were found for age, extraction site, and duration of administration. The incidence of BRONJ increased with age, was greater in the mandible than the maxilla, and was associated with a duration of administration of more than 3 years. Tooth extraction in patients on oral bisphosphonates requires careful consideration of their age, the extraction site, and the duration of administration, and close postoperative follow-up should be carried out to facilitate effective early management.


Barrier Heights for Diels-Alder Transition States Leading to Pentacyclic Adducts: A Benchmark Study of Crowded, Strained Transition States of Large Molecules.
Theoretical characterization of reactions of complex molecules depends on providing consistent accuracy for the relative energies of intermediates and transition states. Here we employ the DLPNO-CCSD(T) method with core-valence correlation, large basis sets, and extrapolation to the CBS limit to provide benchmark values for Diels-Alder transition states leading to competitive strained pentacyclic adducts. We then used those benchmarks to test a diverse set of wave function and density functional methods for the absolute and relative barrier heights of these transition states. Our results show that only a few of the tested density functionals can predict the absolute barrier heights satisfactorily, although relative barrier heights are more accurate. The most accurate functionals tested are ωB97M-V, M11plus, ωB97X-V, PBE-D3(0), M11, and MN15 with MUDs from best estimates less than 3.0 kcal. These findings can guide selection of density functionals for future studies of crowded, strained transition states of large molecules.


Teaching Incision and Drainage: Perceived Educational Value of Abscess Models.
Incision and drainage (I&D) of skin abscesses is an important procedural skill for pediatric emergency medicine providers. Practical skills training using simulation provides an opportunity to learn and gain confidence with this invasive procedure. Our objective was to assess the perceived educational value of 2 versions of an abscess model as part of an educational workshop for teaching I&D. A combined didactic and practical skills workshop was developed for use at 2 national conferences. The didactic content was created through an iterative process. To facilitate hands-on training, 2 versions of an abscess model were created: 1 constructed from a negative mold and the other using a 3-dimensional printer. Participants were surveyed regarding prior experience with I&D, procedural confidence, and perceptions of the educational utility of the models. Seventy physicians and 75 nurse practitioners participated in the study. Procedural confidence improved after training using each version of the model, with the greatest improvements noted among novice learners. Ninety-four percent of physicians, and 99% of nurse practitioners rated the respective models as either "educational" or "very educational," and 97% and 100%, respectively, would recommend the abscess models to others. A combined didactic and practical skills educational workshop using novel abscess models was effective at improving learners' confidence. Our novel models provide an effective strategy for teaching procedural skills such as I&D and demonstrate a novel use of 3-dimensional printers in medical education. Further study is needed to determine if these educational gains translate into improvement in clinical performance or patient outcomes.


Genetic evaluation of paediatric nephrocalcinosis: phenotype-driven genetic panels reveal a rare diagnosis.
Monogenic causes of paediatric nephrocalcinosis are associated with extensive phenotypic variability. We report a 14-year-old male who presented at 8 years of age with incidentally identified nephrocalcinosis alongside growth impairment and dental anomalies. Extensive genetic investigation confirmed a molecular diagnosis of Bartter syndrome type II. This is exceptional in both late presentation and the presence of amelogenesis imperfecta, a very rare association of inherited tubulopathies. Details of the nephrocalcinosis gene panel analysed and associated phenotypes are presented to highlight the utility of a phenotype-driven genetic panel in resolving an atypical presentation of nephrocalcinosis, allowing precise diagnosis, tailored therapy and prognostication.


pH-responsive drug release and real-time fluorescence detection of porous silica nanoparticles.
In this work, pH-sensitive "dual-switch" porous silica (pSiO2) nanoparticles (NPs) were constructed for drug delivery. Poly(acrylic acid) (PAA) was grafting onto the internal and external surfaces of amino groups functionalized porous silica (pSiO2-NH2) NPs by the amidation between the amino groups and the carboxyl groups of PAA for pH triggered drug release. The resultant pSiO2/PAA NPs have an average diameter of 50-60nm and high specific surface area (914m2·g-1). To improve the loading capacity, ZnO quantum dots (QDs) were used to block the partial pores of pSiO2/PAA and the loading capacity reached to 28% for methotrexate (MTX) model drug. The in vitro cellular cytotoxicity test and a hemolysis assay demonstrated that the pSiO2/PAA/ZnO NPs were highly biocompatible and suitable to utilize as drug carriers. The MTX-loaded pSiO2/PAA/ZnO NPs displayed more efficient cytotoxic to HepG2 cells than free MTX. The pSiO2/PAA/ZnO NPs displayed low premature, pH-responsive release and pH-dependent fluorescence. Moreover, pH-dependent fluorescence enables to trace MTX release behavior.


Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2.
Tyrosyl-DNA phosphodiesterase 2 (TDP2) reverses Topoisomerase 2 DNA-protein crosslinks (TOP2-DPCs) in a direct-reversal pathway licensed by ZATTZNF451 SUMO2 E3 ligase and SUMOylation of TOP2. TDP2 also binds ubiquitin (Ub), but how Ub regulates TDP2 functions is unknown. Here, we show that TDP2 co-purifies with K63 and K27 poly-Ubiquitinated cellular proteins independently of, and separately from SUMOylated TOP2 complexes. Poly-ubiquitin chains of ≥ Ub3 stimulate TDP2 catalytic activity in nuclear extracts and enhance TDP2 binding of DNA-protein crosslinks in vitro. X-ray crystal structures and small-angle X-ray scattering analysis of TDP2-Ub complexes reveal that the TDP2 UBA domain binds K63-Ub3 in a 1:1 stoichiometric complex that relieves a UBA-regulated autoinhibitory state of TDP2. Our data indicates that that poly-Ub regulates TDP2-catalyzed TOP2-DPC removal, and TDP2 single nucleotide polymorphisms can disrupt the TDP2-Ubiquitin interface.


[1-9-NαC]-crourorb A1 isolated from Croton urucurana latex induces G2/M cell cycle arrest and apoptosis in human hepatocarcinoma cells.
[1-9-NαC]-crourorb A1 is a cyclic peptide isolated from Croton urucurana Baillon latex, found in midwestern Brazil, that has been shown to exert cytotoxic effects against a panel of cancer cell lines. However, the underlying mechanisms responsible for the crourorb A1-induced cytotoxicity in cancer cells remain unknown. In this study, the effects of crourorb A1 on the viability, apoptosis, cell cycle and migration of Huh-7 (human hepatocarcinoma) cells were investigated. We evaluated the viability of Huh-7 cells treated with crourorb A1 in 2D and 3D collagen cultures and found that cells in 3D culture exhibited increased resistance to crourorb A1 compared to cells in 2D culture (IC50: 62μg/ml versus 35.75μg/ml). Crourorb A1 treatment decreases the viability of Huh-7 cells in a dose- and time-dependent manner and is associated with the induction of apoptosis, in the absence of necrotic cells, through the activation of caspase-3/7 and increased expression of the pro-apoptotic proteins Bak, Bid, Bax, Puma, Bim, and Bad. The effects of crourorb A1 are also associated with G2/M phase cell cycle arrest and increases in cyclin-dependent kinase (CDK1) and cyclin B1 expression. A significant reduction in Huh-7 cell migration induced by crourorb A1 was also observed in the presence of mitomycin C. Finally, we showed that the JNK/MAP pathway, but not ERK signaling, is involved in crourorb A1-induced hepatocarcinoma cell mortality.


A biomechanical analysis of anterior Bankart repair using suture anchors.
Arthroscopic repair of anterior Bankart lesions is typically done with single-loaded suture anchors tied with simple stitch configuration. The knotless suture anchor will have similar biomechanical properties compared with two types of conventional suture anchors. Controlled laboratory study. Fresh-frozen shoulders were dissected and an anteroinferior Bankart lesion was created. For phase 1, specimens were randomized into either simple stitch (SSA) or knotless suture anchors (KSA) and loaded to failure. For phase 2, specimens were randomized into 1 of 4 repair techniques and cyclically loaded then loaded to failure: (1) SSA, (2) suture anchor with horizontal mattress configuration, (3) double-loaded suture anchor with simple stitch configuration, or (4) KSA. Data recorded included mode of failure, ultimate load to failure, load at 2 mm of displacement, as well as displacement during cyclical loading. For phase 1, the load required to 2 mm displacement of the repair construct was significantly greater in SSA (66.5 +/- 21.7 N) than KSA (35.0 +/- 12.5 N, P = .02). For phase 2, there was a statistically significant difference in ultimate load to failure among the 4groups, with both the single-loaded suture anchor with simple stitch (184.0 +/- 64.5 N), horizontal mattress stitch (189.0 +/- 65.3N), and double-loaded suture anchor with simple stitch (216.7 +/- 61.7 N) groups having significantly (P < .05) higher loads than the knotless group (103.9 +/- 52.8 N). There was no statistically significant difference (P > .05) among the 4 groups in displacement after cyclical loading or load at 2 mm of displacement. Both knotless and simple anchor configurations demonstrated similar single loads to failure (without cycling); however, the knotless device required less single load to displace 2 mm. All repair stitches, including simple, horizontal, and double-loaded performed similarly. The findings may suggest that with cyclical loading up to 25 N there is no difference in gapping greater than 2mm, but a macrotraumatic event may demonstrate a difference in fixation during the initial postoperative period. Additional in vivo studies are needed to determine whether these differences affect the integrity of the repair construct and, ultimately, the clinical outcome.


Acute liver failure.
Acute liver failure (ALF) is a rare critical illness with high mortality whose successful management requires early recognition and effective initial management. Though it may result from a wide variety of causes, in the UK and much of the developed world most cases result from paracetamol-induced hepatotoxicity, and administration of antidotal N-acetyl cysteine at first recognition is key. Involvement of local critical care services should occur at an early stage for stabilisation, monitoring and supportive care with parallel discussion with specialist liver centres to identify those patients who may benefit from transfer. Prognostic criteria are applied to identify patients for emergency liver transplantation, and candidates for surgery are prioritised on waitlisting schemes. Outcomes now approach that of elective surgery. However, the majority of cases, and particularly those with paracetamol-induced disease, recover with supportive medical care alone. Overall outcomes for patients with ALF have improved dramatically over the last three decades, but mortality remains unacceptable and further advances in care are required.


Spanish post-menopausal women's viewpoints on hormone therapy.
The purpose of this study was to identify women's socio-demographic and climacteric factors, as well as other variables related to health care, associated with the prescription of the treatment during menopause and to investigate the prevalence of certain conditioning factors in early discontinuation in women aged 40-65 years in a population of post-menopausal women in Spain. Cross-sectional survey. Four of the most inhabited cities in Spain (Madrid, Barcelona, Seville and Valencia). A total of 270 symptomatic post-menopausal women. A personal interview with a semi-structured questionnaire specifically designed to collect information on treatments for climacteric-related complaints. The reasons for HRT, the evaluation of alternative therapies, the reasons for choosing one therapy or another and reasons for discontinuation. Of all the subjects included, 180 were still taking any type of treatment and 90 were former HRT users or had never used HRT. Among the latter, 43% of women expressed fear of the side effects and 38% gave the risk of breast cancer as the main reason for not using HRT. Of them, 58% receive phytoestrogens. Media and negative data from medical journals influenced this attitude in 67% of the women. On the other hand, only 9.4% of HRT users were reluctant to receive the therapy and the main reasons for maintaining HRT were its efficacy against climacteric symptoms, medical prescription and life quality. Side effects and fear of cancer were the most common reasons for not using HRT; and medical prescription, symptomatic improvement and quality of life were the main reasons for using it. Negative data from journals have an important effect on women's attitudes to HRT.


Direct binding to GABARAP family members is essential for HIV-1 Nef plasma membrane localization.
HIV-1 Nef is an important pathogenic factor for HIV/AIDS pathogenesis. Studies have shown that the association of Nef with the inner leaflet of the plasma membrane and with endocytic and perinuclear vesicles is essential for most activities of Nef. Using purified recombinant proteins in pull-down assays and by co-immunoprecipitation assays we demonstrate that Nef binds directly and specifically to all GABARAP family members, but not to LC3 family members. Based on nuclear magnetic resonance (NMR) experiments we showed that Nef binds to GABARAP via two surface exposed hydrophobic pockets. S53 and F62 of GABARAP were identified as key residues for the interaction with Nef. During live-cell fluorescence microscopy an accumulation of Nef and all GABARAP family members in vesicular structures throughout the cytoplasm and at the plasma membrane was observed. This plasma membrane accumulation was significantly reduced after knocking down GABARAP, GABARAPL1 and GABARAPL2 with respective siRNAs. We identified GABARAPs as the first known direct interaction partners of Nef that are essential for its plasma membrane localization.


Incidence of perioperative adverse events in obese children undergoing elective general surgery.
A worldwide increase in the prevalence of obesity has been observed in both developed and developing countries. Few studies have addressed the anaesthetic or perioperative implications of childhood obesity. Children aged 2-16 yr undergoing general surgery were classified using age- and sex-adjusted BMI. Patient characteristic, co-morbidity, and perioperative data were collected to ascertain the risks associated with overweight and obese children. We enrolled 1465 subjects in our study, of which 154 (10.5%) were classified as obese and a further 223 (15.2%) as overweight. After adjusting for age, we identified increased rates of arterial haemoglobin desaturation, difficult mask ventilation, airway obstruction, and bronchospasm in obese children. The relative risk (RR) of adverse respiratory events was higher among obese subjects than non-obese subjects and higher in younger age groups. Controlling for age, adjusted-RR (confidence interval) was 1.49 (1.2-1.86). There was a significant association between obesity and asthma with a higher odds ratio (OR) in younger age groups controlling for age: adjusted-OR=1.8 (1.15-2.82). A significant association was detected between obesity and sleep apnoea controlling for age: adjusted-OR=4.03 (2.37-6.8). These results suggest an increased incidence of perioperative adverse respiratory events in obese children, especially at younger ages.


Photocatalytically induced hydrophilicity influences bone remodelling at longer healing periods: a rabbit study.
Previously, we have reported that photocatalytically active hydrophilicity of the anatase titanium dioxide (TiO₂) nanoparticles coated onto commercially pure titanium discs presented significantly improved hydrophilicity after ultraviolet irradiation. As hydrophilicity has shown enhancement of osseointegration, the in vivo responses were of great interest. The aim of this study was to evaluate whether or not the photo-activated hydrophilicity generated at the time of implant placement has an effect on the longer healing periods for osseointegration. Photocatatytically active nanostructured TiO₂ powder (Degussa P-25), which consists of approximately 80% anatase and 20% rutile, was spin-coated onto commercially pure titanium discs and was heat-treated thereafter. These P25-coated discs were irradiated with ultraviolet (UV) light for the test (+UV) group, and non-irradiated discs were prepared for the control (-UV) group. Both groups of discs were placed in the rabbits' tibiae. After 12 weeks of healing period, histological analysis and gene expression analysis using real-time RT-PCR were performed. From the histological analyses, there were no specific differences between -UV and +UV groups. However, from the gene expression analysis, ALP, RUNX-2 and IL-10 were significantly upregulated for the +UV group compared with the -UV group. The biologically enhancing effect to photocatalytically activated surfaces remained even after 12 weeks of healing time in terms of genetic responses.


Screening method for the detection of aflatoxins, ochratoxin, patulin, sterigmatocystin, and zearalenone in cereals.
A screening method has been developed for the detection of aflatoxins, ochratoxin A, patulin, sterigmatocystin, and zearalenone in cereals. After extraction, the sample is cleaned up by gel filtration. The mycotoxins are separated by thin layer chromatography. The limits of detection are about 5 microgram aflatoxins, 10 microgram ochratoxin A, 50 microgram patulin, 10 microgram sterigmatocystin, and 35 microgram zearalenone/kg.


Orchidectomy alone versus orchidectomy plus radiotherapy in stage I nonseminomatous testicular cancer: a randomized study by the Danish Testicular Carcinoma Study Group.
All Danish patients with stage I nonseminomatous testicular cancer diagnosed between December 1980 and January 1984 entered a randomized study comparing irradiation of retroperitoneal lymph nodes with surveillance only after orchidectomy. Twenty-four of the seventy-nine patients in the observation-only group have relapsed, three patients relapsing more than 2 years after orchidectomy. Ten of the seventy-three patients receiving irradiation have relapsed, all within 10 months after orchidectomy. The median time to relapse in both groups was 4.5 months. Irradiation prevented retroperitoneal relapses. Thirty-three of the relapsed patients were rendered disease free with chemotherapy, and one is still being treated. Four deaths have occurred, all unrelated to testicular cancer or antineoplastic treatment. Absence of embryonal carcinoma and presence of teratocarcinoma correlated with improved relapse-free survival. Patients with increased serum concentrations of tumour markers before orchidectomy had an increased risk of relapse. Surveillance-only is a reasonable treatment strategy in clinical stage I nonseminomatous testicular cancer. Preferably control and treatment of relapses should take place in specialized centres.


Active compression-decompression resuscitation and impedance threshold device for out-of-hospital cardiac arrest: a systematic review and metaanalysis of randomized controlled trials.
Active compression-decompression resuscitation and impedance threshold device are proposed to improve survival of patients of cardiac arrest by lowering intrathoracic pressure and increasing cardiac output. The results of clinical studies of active compression-decompression resuscitation or impedance threshold device were controversial. This metaanalysis pooled results of randomized controlled trials to examine whether active compression-decompression resuscitation or impedance threshold device would improve outcomes of out-of-hospital cardiac arrest in comparison with standard cardiopulmonary resuscitation and to explore factors modifying these effects. Medline and Embase were searched from inception to September 2013. Randomized controlled trials comparing active compression-decompression resuscitation or impedance threshold device with standard cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients were selected. There were no restrictions for language, population, or publication year. Data on study characteristics, including patients, intervention details, and outcome measures, were independently extracted. Fifteen trials, including 16,088 patients, were identified from 331 potentially relevant references. Return of spontaneous circulation was designated as the primary outcome. The pooled result showed no significant improvement in return of spontaneous circulation by active compression-decompression resuscitation or impedance threshold device in comparison with standard cardiopulmonary resuscitation (risk ratio, 1.04; 95% CI, 0.93-1.16; I, 46%). There was also no significant difference in survival or neurologic outcome at hospital discharge between active compression-decompression resuscitation or impedance threshold device and standard cardiopulmonary resuscitation. The meta-regression indicated that this minimal effect might be modified by two important prognostic factors, that is, witnessed status and response time. After adjustment of these two factors, impedance threshold device appeared to improve return of spontaneous circulation, which could be further augmented by advanced airway use. Active compression-decompression resuscitation or impedance threshold device seemed not to improve return of spontaneous circulation in out-of-hospital cardiac arrest patients. The meta-regression indicated two probable prognostic factors causing this minimal effect. Nonetheless, these findings referred to differences between trials and could not necessarily be extrapolated to individual patients. The individual patient-level extrapolation may need to be solved by a future randomized controlled trial.


[Attitudes towards physical disability in the Middle Ages].
The article describes attitudes to disability and physically disabled people, taking into account the aspect of ethical and social location, what physically disabled meant in societies, and ways to solve the problems of disability. The article is based on studies of disability and historical sources. Christ's attitude shown in the Gospels changed the traditional cultures of the ancient treatment of disability in terms of it being seen as a penalty of the divine. The development of Christianity caused a gradual expansion of the ideas of charity, at the same time stepping up care and material support to all those physically disabled in need. Care of the disabled is based mostly on charity. Church activities supported, by the structure of the State and private individuals, was of paramount importance. Medieval society felt responsible for disabled people.


5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease.
Clinical observations have suggested that ritanserin, a 5-HT(2A/C) receptor antagonist may reduce motor deficits in persons with Parkinson's Disease (PD). To better understand the potential antiparkinsonian actions of ritanserin, we compared the effects of ritanserin with the selective 5-HT(2A) receptor antagonist M100907 and the selective 5-HT(2C) receptor antagonist SB 206553 on motor impairments in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-treated mice exhibited decreased performance on the beam-walking apparatus. These motor deficits were reversed by acute treatment with L-3,4-dihydroxyphenylalanine (levodopa). Both the mixed 5-HT(2A/C) antagonist ritanserin and the selective 5-HT(2A) antagonist M100907 improved motor performance on the beam-walking apparatus. In contrast, SB 206553 was ineffective in improving the motor deficits in MPTP-treated mice. These data suggest that 5-HT(2A) receptor antagonists may represent a novel approach to ameliorate motor symptoms of Parkinson's disease.


Anti-hTERT siRNA-Loaded Nanoparticles Block the Growth of Anaplastic Thyroid Cancer Xenograft.
The high frequency of hTERT-promoting mutations and the increased expression of hTERT mRNA in anaplastic thyroid cancer (ATC) make TERT a suitable molecular target for the treatment of this lethal neoplasm. In this study, we encapsulated an anti-hTERT oligonucleotide in biocompatible nanoparticles and analyzed the effects of this novel pharmaceutical preparation in preclinical models of ATC. Biocompatible nanoparticles were obtained in an acidified aqueous solution containing chitosan, anti-hTERT oligoRNAs, and poloxamer 188 as a stabilizer. The effects of these anti-hTERT nanoparticles (Na-siTERT) were tested in vitro on ATC cell lines (CAL-62 and 8505C) and in vivo on xenograft tumors obtained by flank injection of CAL-62 cells into SCID mice. The Na-siTERT reduced the viability and migration of CAL-62 and 8505C cells after 48-hour incubation. Intravenous administration (every 48 hours for 13 days) of this encapsulated drug in mice hosting a xenograft thyroid cancer determined a great reduction in the growth of the neoplasm (about 50% vs. untreated animals or mice receiving empty nanoparticles), and decreased levels of Ki67 associated with lower hTERT expression. Moreover, the treatment resulted in minimal invasion of nearby tissues and reduced the vascularity of the xenograft tumor. No signs of toxicity appeared following this treatment. Telomere length was not modified by the Na-siTERT, indicating that the inhibitory effects of neoplasm growth were independent from the enzymatic telomerase function. These findings demonstrate the potential suitability of this anti-TERT nanoparticle formulation as a novel tool for ATC treatment. Mol Cancer Ther; 17(6); 1187-95. ©2018 AACR.


Transport model predictions of 225Ac production cross sections via energetic p, d and α irradiation of 232Th targets.
Monte Carlo transport codes PHITS and MCNP6 were used to calculate the production cross sections of 225,227Ac, 227,229Th, 223,225Ra, and 229,230,231Pa via the bombardment of a232Th target with energetic protons, deuterons, and α-particles. The incident projectile energies ranged between 10 and 800 MeV/nucleon. When possible, the predicted production cross sections were compared with the available experimental data and other predictions. The degree of the codes' abilities to match the measured data provides a qualitative assessment of the codes' abilities to predict data from similar, but unmeasured, projectile/target systems. In addition, a comparison between calculated cross sections and data may provide insight into possible improvements in the physics models employed by those transport codes.


Diurnal variations of interleukin-1 beta mRNA and beta-actin mRNA in rat brain.
Interleukin-1 beta (IL-1 beta) is posited to play an important physiological role in brain functions in addition to its better defined role in pathology. The experiments described herein were performed to determine if IL-1 beta mRNA and beta-actin display diurnal rhythms in various areas of brain. Rats were sacrificed at 4 h intervals across a 12:12 h light/dark cycle. Hypothalamic, hippocampal and cortical IL-1 beta mRNA peaked just after lights were turned on, declined slightly during the remaining light period and stayed low in the dark. There were no significant changes in IL-1 beta mRNA in brain stem or cerebellum samples. beta-actin mRNA levels were relatively constant across the day in the hypothalamus, brain stem and cerebellum. However, beta-actin mRNA levels were lower during the day than during the night in the hippocampus and cortex.


Partial closure and other techniques in pilonidal surgery: an assessment of 157 cases.
The report is a retrospective study of 157 patients with pilonidal disease. The period in hospital, the healing time, and the rates of wound breakdown and sinus recurrence were documented following four different methods of management. After incision and drainage of the pilonidal abscess, later excision was necessary in less than 40 per cent of patients. Elective excision of the granulation tissue and skin, with partial closure of the defect, gave better results than excision and primary suture.


Systolic anterior motion of the mitral valve associated with acute type A aortic dissection: a case report describing one-step surgery of ascending aortic replacement and interventricular septal myectomy.
Systolic anterior motion of the mitral valve associated with acute type A aortic dissection is rare in daily clinical practice. The prevention of systolic anterior motion is important, because once it occurs, the hemodynamics may become unstable, leading to a critical situation. In the surgical procedure to treat systolic anterior motion, the prevention of new iatrogenic aortic intimal tears is important in the context of acute type A aortic dissection. We present a case of systolic anterior motion in a 68-year-old woman with an acute type A aortic dissection and suspected acute relative adrenal insufficiency. Preoperative transthoracic echocardiography revealed left ventricular outflow tract obstruction due to systolic anterior motion without left ventricular hypertrophy and interventricular septal bulging due to a narrow aorto-mitral angle. We successfully performed a one-step surgery for ascending aortic replacement and interventricular septal myectomy using the needle stick technique for the treatment of systolic anterior motion. Concomitant interventricular septal myectomy using the needle stick technique with thoracic aortic replacement is a safe and feasible technique. Interventricular septal myectomy may be effective in preventing postoperative unstable hemodynamics due to systolic anterior motion in the management of acute aortic dissection.


Stress relaxation of deformed gel in a good solvent.
A method for obtaining elastic moduli and frictional properties of gel chains, diagonal and off-diagonal elements of a friction tensor, from a tensile force relaxation of cylindrical gel that is stretched in a good solvent is presented. The theory to describe the relaxation is developed on the assumption that an off-diagonal element of the friction tensor is nonzero and compared with experimental results obtained for the poly(acrylamide) gel in water. The experiments revealed that the tensile force relaxation, F(t) at a long t, was described by a function: F(t)=A(Fi-FS) x exp(-t/tau)+FS, where Fi, FS, and A, respectively, were tensile forces at the initiation and the steady state, and a constant. The tau was found to be proportional to a square of radius of the gel. The experiments also revealed that the elastic force relaxation was synchronized with a change of the gel diameter. The theory well elucidates the experimental results to reveal the bulk and shear moduli, and the diagonal and off-diagonal elements of friction tensor.


Mixture-Based Screening of Focused Combinatorial Libraries by NMR: Application to the Antiapoptotic Protein hMcl-1.
We report on an innovative ligand discovery strategy based on protein NMR-based screening of a combinatorial library of ∼125,000 compounds that was arranged in 96 distinct mixtures. Using sensitive solution protein NMR spectroscopy and chemical perturbation-based screening followed by an iterative synthesis, deconvolutions, and optimization strategy, we demonstrate that the approach could be useful in the identification of initial binding molecules for difficult drug targets, such as those involved in protein-protein interactions. As an application, we will report novel agents targeting the Bcl-2 family protein hMcl-1. The approach is of general applicability and could be deployed as an effective screening strategy for de novo identification of ligands, particularly when tackling targets involved in protein-protein interactions.


Supply curves for using powder river basin coal to reduce sulfur emissions.
Supply curves were prepared for coal-fired power plants in the contiguous United States switching to Wyoming's Powder River Basin (PRB) low-sulfur coal. Up to 625 plants, representing approximately 44% of the nameplate capacity of all coal-fired plants, could switch. If all switched, more than dollars 8.8 billion additional capital would be required and the cost of electricity would increase by up to dollars 5.9 billion per year, depending on levels of plant derating. Coal switching would result in sulfur dioxide (SO2) emissions reduction of 4.5 million t/yr. Increase in cost of electricity would be in the range of 0.31-0.73 cents per kilowatt-hour. Average cost of S emissions reduction could be as high as dollars 1298 per t of SO2. Up to 367 plants, or 59% of selected plants with 32% of 44% nameplate capacity, could have marginal cost in excess of dollars 1000 per t of SO2. Up to 73 plants would appear to benefit from both a lowering of the annual cost and a lowering of SO2 emissions by switching to the PRB coal.


A Case Report of Vulvar Leiomyoma: A Rare Pathological Entity.
Smooth muscle tumors, known as leiomyomas, are benign and can grow anywhere in the body, but the uterine myometrium is the most common site. Vulvar leiomyomas are uncommon and rare. We report a case of a 25-year-old female P (para) 1 L (live) 1 with a previous normal vaginal delivery, who presented two painless swelling of in vulva for one year. The urethral meatus deviated to the left side. After surgical excision, a histopathological examination was performed that confirmed leiomyoma. The patient was discharged after an uneventful postoperative period. A vulvar leiomyoma tumor is often mistaken for a Bartholin cyst, and it is challenging to distinguish between benign and malignant types of vulvar leiomyomas, making diagnosis extremely challenging.


Thyroid and Assisted Reproduction Technologies: A Brief Clinical Update with Recommendations for Practice.
Infertility is a common disease that in about one third of cases has a female cause and often requires assisted reproduction technologies (ART) to conceive. Also thyroid autoimmunity (TAI), with or without hypothyroidism, is a common disease, particularly in females, and referral for endocrine consultation is not infrequent. In the last 15 years a remarkable amount of studies has been published that investigated the pathophysiology of women suffering from TAI, who undergo ART. Due to insufficient sample size, data about the association between infertility and TAI/subclinical hypothyroidism are conflicting. In relation to pregnancy rate, miscarriage, and live births (primary outcomes) data of the literature do not allow to clearly demonstrating an unfavorable impact attributable to TAI/subclinical hypothyroidism; however, secondary outcomes like ovarian reserve or oocytes quality look like worsened. For sure, the therapeutic regimens used for controlled ovarian hyperstimulation (COH) induce a deterioration of thyroid function in patients suffering from TAI [with or without Levothyroxine (LT4) treatment]. This picture places patients in a condition of increased risk of developing untimely TSH elevation during fertilization; then, it is reasonable that a patient, above all if thyroid antibody positive, would have a TSH value <2.5mIU/L before undergoing COH, and that would be strictly monitored to start or increase LT4 treatment, when necessary.


Investigations on microbial diversity of Jakrem hot spring, Meghalaya, India using cultivation-independent approach.
Jakrem hot water spring is located in the West Khasi Hill District of the state of Meghalaya, and is one of the most popular hot springs of the state. There is a populist belief among the inhabitants and people that the hot spring water has got curative properties against various skin ailments. This is the first report on V3 hyper-variable region of 16S rDNA metagenome sequence employing Illumina platform to profile the microbial community of this less known hot spring from Meghalaya, India. Metagenome comprised of 10, 74,120 raw sequences with a sequence length of 151 bp and 56.35% G + C content. Metagenome sequence information is now available at NCBI, SRA database accession no. SRP056897. A total of 8, 77, 364 pre-processed reads were clustered into 694 OTUs (operational taxonomical units) comprising of 14 bacterial phyla including unknown phylum demonstrating 49 families. Hot spring bacterial community is dominated by Firmicutes (61.60%), Chloroflexi (21.37%), Cyanobacteria (12.96%) and unclassified bacteria (1.2%) respectively.


HPLC-MS/MS methods for the quantitative analysis of 5-oxoproline (pyroglutamate) in rat plasma and hepatic cell line culture medium.
5-Oxoproline (5-OP; pyroglutamate) is an intermediate in the biosynthesis of the endogenous tripeptide glutathione and has been seen to be elevated in the biofluids and tissues of rats following the administration of glutathione-depleting hepatotoxic xenobiotics such as acetaminophen (paracetamol), bromobenzene and ethionine. As 5-OP is a potential biomarker for hepatotoxicity HPLC-MS/MS methods have been developed for its quantification in in vitro cell culture media and rat plasma. For the cell culture media the lower limit of quantification (LLOQ), defined as the lowest concentration on the calibration curve, was 10 ng/ml. Minimal carry over was observed for cell culture media between injections (less than 5% at all concentrations examined), precision and accuracy were generally better than 20% for within and between day analyses. For rat plasma a LLOQ of 50 ng/ml was obtained. Carry over for plasma was less than 5% for all concentrations, within and between batch accuracy and precision were generally better than 20%. The methods were linear for both sample types from the LLOQ up to 1 μg/ml. For samples obtained from rats subjected to chronic administration of the hepatotoxin methapyrilene, concentrations of 5-OP were not observed to increase significantly at any time point compared to controls. 5-OP was also determined in the culture media of human liver epithelial (THLE) cells transfected with cytochrome P450 2E1 (THLE-2E1). Following exposure of THLE-2E1 cells to acetaminophen, large increases in the concentrations of 5-OP were observed, which correlated with reduced cellular glutathione content and with cell toxicity. These results show that LC-MS/MS can be used to perform rapid, sensitive, and quantitative determination of 5-OP in vivo and in vitro and will enable additional investigations into the utility of 5-OP as a biomarker of liver drug-induced liver injury.


The efficacy of resection of an intradural extramedullary foramen magnum cavernous malformation presenting with repeated subarachnoid hemorrhage: a case report.
Intradural extramedullary cavernous angiomas of the central nervous system are a rare type of cavernous angioma, but they can cause fatal subarachnoid hemorrhage. The efficacy of resection for this type of cavernous malformations remains uncertain. This is the first report to recommend surgical resection of these types of lesions regardless of the fatal condition. Our patient was a 70-year-old Japanese man who experienced a sudden onset of an occipital headache, followed by bilateral abducens nerve palsy. Magnetic resonance imaging revealed a small amount of hemorrhage in both of the lateral ventricles and an intradural extramedullary mass lesion in the left side of his foramen magnum. Two weeks after the appearance of initial symptoms, he became comatose. A computed tomography scan showed an increase in the subarachnoid intraventricular hemorrhaging and of the acute hydrocephalus. Following ventricular drainage, total tumor resection was performed using the lateral suboccipital transcondylar approach in conjunction with a first cervical hemilaminectomy. We observed a grape-like vascular-rich tumor with calcification that was adhering tightly to the wall of his left vertebral artery. A histopathological examination of the surgery specimen identified it as a cavernous angioma. After placement of a ventriculoperitoneal shunt and 2 months of rehabilitation, he recovered completely. An intradural extramedullary foramen magnum cavernous malformation is quite rare. The fragile surface of our patient's lesion was causing repeated subarachnoid hemorrhage and consequently progressive fatal neurological deterioration. Surgical resection of the lesion to prevent repeated hemorrhage was performed and he recovered fully. Therefore, we recommend surgical resection of the lesion regardless of the potentially fatal condition.


The efficacy and safety of aspirin in preventing venous thrombosis in major orthopedic surgery: An updated meta-analysis of randomized controlled trials.
Major orthopedic surgery, including hip and knee replacement and lower extremity trauma fractures surgery, is associated with a high risk of venous thromboembolism (VTE), especially proximal deep vein thrombosis (DVT), and pulmonary embolism (PE), and is linked with high morbidity and mortality rates. Chemical anticoagulation is routinely used to prevent VTE, with previous meta-analyses reporting on the efficacy and safety of aspirin and other anticoagulants, however, opinions are divided. In the past 2 years, several large randomized controlled trials have been published, therefore, we reanalyzed aspirin efficacy and safety when compared with other anticoagulants in preventing VTE in major orthopedic surgery. Using PubMed, The Cochrane Library, Embase, and Web of Science databases, we conducted a RCT search in August 2023. The main outcomes included VTE, proximal DVT or PE. Additional outcomes included bleeding events, wound complications, wound infections, blood transfusions, and death events. In total, 17 eligible articles, involving 29,522 patients (15,253 aspirin vs 14,269 other anticoagulant cases), were included. Primary outcomes showed that VTE incidence was more high in the aspirin group when compared with other anticoagulants (risk ratio [RR] = 1.45, 95% confidence interval [CI] = 1.18-1.77, P = .0004) and proximal in the aspirin group the DVT and/or PE incidence was significantly higher in the aspirin group when compared with other anticoagulants (RR = 1.19, 95% CI = 1.02-1.39, P = .03). No significant secondary outcome differences were identified in the aspirin group when compared with other anticoagulants (bleeding events [RR] = 0.83, 95% CI = 0.63-1.10, P = .20); wound complications (RR = 0.45, 95% CI = 0.20-1.04, P = .06); wound infection (RR = 1.08, 95% CI = 0.85-1.38, P = .53); blood transfusion events (RR = 1.00, 95% CI = 0.84-1.19, P = 1.00) and death events (RR = 1.11, 95% CI = 0.78-1.57, P = .55). Our updated meta-analysis showed that aspirin was inferior to when compared with other anticoagulants in VTE-related orthopedic major surgery, including proximal DVT and/or PE, and was more likely to form VTE. No differences between groups were identified for bleeding, wound complications, wound infections, transfusion, or death events.


Exercise Training at Maximal Fat Oxidation Intensity for Older Women with Type 2 Diabetes.
The purpose of this study was to investigate the pleiotropic effects of 12 weeks of supervised exercise training at maximal fat oxidation (FATmax) intensity on body composition, lipid profile, glycemic control, insulin sensitivity and serum adipokine levels in older women with type 2 diabetes. Thirty-one women with type 2 diabetes, aged 60 to 69 years, were randomly allocated into exercise and control groups. Body composition, lipid profile, blood glucose, insulin resistance and serum leptin and adiponectin concentrations were measured before and after the intervention. Exercise group (n=16) walked at individualized FATmax intensities for 1 h/day for 3 days/week over 12 weeks. No dietary intervention was introduced during the experimental period. Maximal fat oxidation rate was 0.37±0.10 g/min, and occurred at 37.3±7.3% of the estimated VO2max. Within the exercise group, significant improvements were observed for most of the measured variables compared to non-exercising controls; in particular, the FATmax program reduced body fat% (p<0.001), visceral fat% (p<0.001), and insulin resistance (p<0.001). There was no significant change in daily energy intake for all participants during the intervention period. These results suggest that individualized FATmax training is an effective exercise training intensity for managing type 2 diabetes in older women.


Serotypes and virulence genes of ovine non-O157 Shiga toxin-producing Escherichia coli in Switzerland.
Sixty ovine STEC strains were examined with the aim (i) to serotype the strains, (ii) to characterize virulence factors, and (iii) to discuss possible associations between these factors and to assess the potential pathogenicity of these strains for humans. The 60 sorbitol-positive, non-O157 STEC strains belonged to 19 O:H serotypes, whereas 68% were of five serotypes (O87:H16, O91:H-, O103:H2, O128:H2, O176:H4). 52% belonged to serotypes reported in association with HUS. Five serotypes were not previously reported in sheep strains. Of the 47 strains encoding for stx1 variants, 57% were stx1c- and of the 45 encoding for stx2 variants, 80% were stx2d-positive. Eighty-two percent of the strains showed further putative virulence factors: 13% were eae-, 60% ehxA- and 67% saa-positive. The associations between harboring (i) eae and stx1, stx2, ehxA or no saa and (ii) saa and stx1c or stx2d were significant (P<0.05). The strains belonged to 27 seropathotypes (association between serotypes and virulence factors), but 57% belonged to only six and O91:H-stx1 stx2d saa and O128:H2 stx1c stx2d ehxA saa were the most common. Seven of the eight intimin-positive strains harbored eae. Four strains of serotype O103:H2 and O121:H10 harboring stx2, eae and ehxA showed virulence factors typical for strains associated with severe human disease. However, according to the virulence factors, the majority of the ovine non-O157 STEC strains are assumed low-virulence variants. Nevertheless, as long as the contribution and interaction of these factors in milder disease remains unclear P, a certain risk for humans cannot be excluded.


Ultrasound changes within the liver after total pancreatectomy and intrahepatic islet cell autotransplantation.
Intrahepatic infusion is the most common method of islet autotransplantation. Structural and functional changes within the liver may result from a number of factors, including embolization of the terminal branches of the portal vein, the effects of high insulin concentration on surrounding hepatocytes or responses to the death of admixed exocrine tissue. Awareness of the potential changes in the appearance of the liver on ultrasonography (USS), together with an assessment of liver function, is important in the postoperative surveillance of these patients. We retrospectively reviewed 83 patients who underwent total pancreatectomy between 1993 and 2006. Thirty-three patients had total pancreatectomy alone (control group) and 50 patients underwent total pancreatectomy and islet autotransplantation (islet group). The islets were infused into the left lobe of the liver through the middle colic or recannalated umbilical vein. All patients underwent USS as part of their hepaticojejunostomy surveillance (initially every 6 months and then yearly). "Echogenic nodularity" of the liver was observed in 25% of the islet group of patients and in none of the control group patients (P=0.03). These USS changes occurred from 6 to 12 months after islet autotransplantation and were not associated with any significant loss of liver function or increase in insulin requirements. The islet group had significantly less insulin requirement compared with the control group (P<0.01). Echogenicity with a nodular appearance is a common ultrasonographic finding in the liver after intrahepatic islet autotransplantation. These changes do not seem to adversely affect liver function or insulin requirement. Appreciating these changes is important to avoid misinterpretation or over-interpretation of postoperative USS images.


Wound Gel with Antimicrobial Effects Based on Polyvinyl Alcohol and Functional Aryloxycyclotriphosphazene.
A silver-containing gel based on polyvinyl alcohol and aryloxycyclotriphosphazene containing β-carboxyethenylphenoxy and p-formylphenoxy groups has been developed. Phosphazene was synthesized via the Doebner reaction from hexakis[(4-formyl)phenoxy]cyclotriphosphazene and malonic acid and characterized by 1H, 13C, and 31P NMR spectroscopy and MALDI-TOF mass spectrometry. The study of the gel using scanning electron microscopy showed that the gel contains open pores and can absorb wound exudate. The maximum water absorption capacity of the gel was 272%, which was reached after 80 min of testing. The antimicrobial activity of the obtained silver-containing gel was evaluated using the diffusion method. The gel was found to inhibit the growth of the main microorganisms in contact with the skin: the bacteria S. aureus, P. aeruginosa, E. coli, B. subtilis, S. epidermidis, and C. stationis and the fungus C. albicans. The study of the wound-healing effect of the gel in vivo showed a decrease in the wound area of the rabbit hind limb by 91.43% (p < 0.05) on the 10th day of observation and a decrease in the content of C-reactive protein in the rabbit blood serum by 1.3 times (p < 0.05).


Disruption of tight junctions contributes to hyposalivation of salivary glands in a mouse model of type 2 diabetes.
Tight junction (TJ) plays an important role in regulating paracellular fluid transport in salivary glands; however, little is known about the involvement of TJs in diabetes salivary glands. This study aimed to investigate the alterations of TJs and their possible contribution in diabetes-induced hyposalivation. Here, we observed that the morphologies of submandibular glands (SMGs) were impaired, characterized by enlarged acini accumulation with giant secretory granules, which were significantly reduced in atrophic ducts in SMGs of db/db mice, a spontaneous model of type-2 diabetes. However, the secretory granules were increased and scattered in the acini of diabetes parotid glands (PGs). Other ultrastructural damages including swollen mitochondria, expansive endoplasmic reticulum, and autophagosomes were observed in the diabetes group. The levels of TJ proteins including claudin-1 (Cldn1) and claudin-3 (Cldn3) were increased, whereas those of claudin-4 (Cldn4), occludin (Ocln), and zonula occludens-1 (ZO-1) were decreased in SMGs of db/db mice. Higher Cldn1 and Cldn3 and lower claudin-10 (Cldn10) and Ocln levels were observed in PGs of diabetes mice. Taken together, the structures of SMGs and PGs were impaired in diabetes mice, and the disruption of TJ integrity in both SMGs and PGs may contribute to diabetes-induced hyposalivation.