Adenoid cystic carcinoma of the lacrimal gland.
This is a retrospective analysis of the 50-year University of Florida experience treating adenoid cystic carcinoma of the lacrimal gland with radiation therapy. Between 1965 and 2015, 8 patients with adenoid cystic carcinoma of the lacrimal gland received radiation therapy with curative intent. Four patients received postoperative radiation therapy and 4 received definitive radiation therapy alone. The median follow-up was 3.3 years (range, 0.3 to 11.2 years). All 4 patients who received postoperative radiation therapy received 74.4 Gy. The 4 patients who received radiation therapy alone received a median dose of 72.3 Gy (range, 70.0 to 74.4 Gy). The overall survival rates at 5 and 10 years were 25% and 13%, respectively. The cause-specific survival rates at 5 and 10 years were 29% and 14%, respectively. The local control and freedom from metastases rates at 5 and 10 years were both 43%. Local recurrences occurred in 50% of patients, and distant metastatic disease occurred in 38% of patients. No patients experienced acute complications of treatment that warranted a treatment break. Two patients experienced bone exposure as late complications of treatment. The results of this study illustrate the propensity for adenoid cystic carcinoma of the lacrimal gland to recur both locally and with distant metastases despite aggressive local treatment measures. This study also demonstrates the relatively poor outcomes for individuals with this type of tumor.


RNA interference and the vaccine effect of a subolesin homolog from the tick Rhipicephalus haemaphysaloides.
Subolesin is a well-characterized protective antigen in many ticks and, thus, it is potentially useful in the development of a broad-spectrum vaccine or an autocidal gene silencing strategy to control tick infestations. A subolesin homolog was cloned from the tick Rhipicephalus haemaphysaloides, which is widespread in China, by rapid amplification of complementary DNA (cDNA) ends. Its full-length cDNA was 1386 base pairs (bp), containing a 483 bp open reading frame with a predicted molecular mass of 18.7 kilodaltons and an isoelectric point of 9.26. The subolesin protein had a typical nuclear localization signal in its amino-terminus. The full-length cDNA of R. haemaphysaloides showed 52 and 80% identities to those from Ixodes scapularis and R. microplus, respectively, whereas amino acid sequence alignments showed 80 and 97% identities, respectively. Native subolesin was recognized in the unfed tick midgut by an antibody against recombinant subolesin. Transcriptional analysis showed that subolesin was expressed in the tick's four developmental stages and in all of the tissues examined, except for the synganglion. The pathogen Babesia microti induced the subolesin transcript by fourfold. Subolesin gene silencing by RNA interference significantly decreased the larval engorgement rate, the attachment rate and body weight of engorged nymphs, and the body weight and attachment and engorgement rates of adults, as well as the egg weight per female tick. Vaccinating mice and rabbits with recombinant subolesin induced a significant protective effect, resulting in a reduction of blood feeding and oviposition. These results encourage further studies of using subolesin to control tick infestations in China.


Automatic P-wave analysis of patients prone to atrial fibrillation.
A method is presented for automatic analysis of the P-wave, based on lead II of a 12-lead standard ECG, in resting conditions during a routine examination for the detection of patients prone to atrial fibrillation (AF), one of the most prevalent arrhythmias. First, the P-wave was delineated, and this was achieved in two steps: the detection of the QRS complexes for ECG segmentation, using a wavelet analysis method, and a hidden Markov model to represent one beat of the signal for P-wave isolation. Then, a set of parameters to detect patients prone to AF was calculated from the P-wave. The detection efficiency was validated on an ECG database of 145 patients, including a control group of 63 people and a study group of 82 patients with documented AF. A discriminant analysis was applied, and the results obtained showed a specificity and a sensitivity between 65% and 70%.


The Use of Opioids and Pain Medications in the Management of Postoperative Pain in Total Knee Arthroplasty Patients: A Retrospective Study.
The opioid crisis amplified the concern for the appropriate use of opioids. Our study aims to investigate the pain levels and amount of opiates needed during the first three days following total knee arthroplasty (TKA), whereby Drug Enforcement Administration (DEA) Schedule II oral opiates are not available. A year-long retrospective review of adult patients who underwent TKA was conducted. The postoperative pain scores and mean morphine equivalents (MME) were measured. These outcomes were assessed according to demographics, anesthesia, and analgesia used. For our 78 patients, there was no statistical difference for stratification by baseline characteristics except in spinal anesthesia, which decreased pain on the first day. Conversely, MME increased to its significantly highest of 14.22 ± 29.58 mg on day 3. The effect was noted for patient-controlled analgesia where patients with intravenous analgesia received less opioid than those on epidural analgesia on postoperative day one. Using a similar regimen of analgesia, postoperative pain following TKA would be controlled by a relatively low amount of opioids by the third postoperative day. Spinal anesthesia and patient-controlled epidural analgesia were linked to better pain control and less opioid needed.


Gastrointestinal hemorrhage in paralyzed and neurologically impaired patients: contribution of reflux esophageal disease.
The role of gastroesophageal reflux (GER) and reflux esophagitis in the pathogenesis of gastrointestinal hemorrhage was assessed in 13 male patients with chronic paralysis or neurologic impairment. Nine of the 13 patients initially presented for barium meal examination to evaluate anemia, hematemesis, heme-positive stools, or melena. Six of the 9 had radiographic evidence, confirmed by upper gastrointestinal (GI) endoscopy, of esophagitis with or without stricture without other upper GI tract lesions. Notably absent were antecedent symptoms of GER such as heartburn or dysphagia. Careful examination of the esophagus, although difficult, must be an integral part of the evaluation for anemia and/or gastrointestinal blood loss in paralyzed patients.


Cholecystokinin octapeptide, proglumide, and passive avoidance in rats.
Rats were conditioned to avoid a darkened chamber using electric footshock (0.25 mA for 2 sec). Cholecystokinin octapeptide (CCK-8), a CCK-8 antagonist proglumide, or 0.9% NaCl solution was injected immediately following the footshock to study the effect upon passive avoidance behavior. The passive avoidance behavior was observed one day following the conditioning footshock and treatment. CCK-8 produced a reduction of the passive avoidance latency of rats at doses ranging from 30 micrograms/kg to 500 micrograms/kg. Proglumide (5 mg/kg) was able to block the CCK-8 effect on rat passive avoidance conditioning. Proglumide by itself at a dose of 2 mg/kg decreased the latency to enter the darkened chamber. Endogenous CCK-8 activity may be involved in passive avoidance conditioning in rats.


The effect of minoxidil on endothelial cells in vitro.
Minoxidil - a therapeutic agent used in the control of hypertension and which has been implicated in modulation of hair follicle activity - has been shown to influence certain aspects of the physiology of cultured endothelial cells. It suspends cell proliferation in a reversible manner, appears to influence cell morphology in a dose dependent way, does not significantly alter (qualitatively) protein synthesis and does not inhibit cell migration. These results demonstrate similarities between endothelial cells and keratinocytes and dermal fibroblasts and differences between endothelial cells and dermal papilla cells, follicular root sheath fibroblasts and neutrophils in their response to this agent.


Molecular basis of Hb H and AEBart's diseases in the Lao People's Democratic Republic.
As compared to other neighboring countries, limited information on α-thalassemia diseases is available for Lao PDR. We reported for the first time a genetic diversity associated with Hb H and AEBart's diseases in Laos patients. Study was done on Laos patients with Hb H disease (n = 14) and AEBart's disease (n = 14) whose blood specimens were transferred to our laboratory for the investigation of thalassemia. Hematological parameters were recorded. Hb analysis was done using a capillary electrophoresis system. α- and β-globin genotypes were determined using PCR and related techniques. Hb and DNA analyses identified Hb H disease resulted from [--SEA /-α3.7 , βA /βA ] (n = 7), [--THAI /-α3.7 , βA /βA ] (n = 1), Hb H-Constant Spring (CS) disease (--SEA /αCS α, βA /βA ; n = 5), and Hb H-IVSI-117 (--SEA /ααIVSI-117G>A , βA /βA ; n = 1). For those of the AEBart's disease (n = 14), five were found to be AEBart's-CS disease [--SEA /αCS α, βE /βA ], two had [--THAI /αCS α, βE /βA ] genotype, six had AEBart's disease with (--SEA /-α3.7 , βE /βA ) genotype, and the remaining one was a patient with AEBart's-Pakse' [--SEA /αPS α, βE /βA ] disease. These --THAI and αIVSI-117G>A mutations are reported herein for the first time in Laos population. Accurate diagnosis in most cases was obtained after DNA analysis. This study demonstrates the diverse heterogeneity and highlights the importance of molecular diagnosis of α-thalassemia diseases in Laos population. Data on the molecular basis of α-thalassemia should prove useful for setting up a molecular diagnostic testing for thalassemia in Laos and further hemoglobin genetic study in the region.


Obestatin attenuated doxorubicin-induced cardiomyopathy via enhancing long noncoding Mhrt RNA expression.
The emergence of side-effect of doxorubicin in cardiomyopathy and heart failure has led to the search for diverse strategies to prevent its cytotoxic effects. This study was to determine the role of obestatin on doxorubicin-induced cardiomyocytes apoptosis and possible underlying mechanism. Sprague Dawley rats were divided into 3 groups and received treatment for a total of 6 weeks: group1, untreated normal rats; group2, Doxorubicin-induced heart cardiomyopathy (DC) rats; and group3, obestatin treated HC rats. Doxorubicin (2.5mg/kg) or obestatin (100μg/kg/d) were discontinuously administered via intraperitoneal injection. Primary cardiomyocytes and H9C2 cell line were used for in vitro experiments. Mhrt and Nrf2 (nuclear factor erythroid 2 -related factor 2) mRNA expressions were determined using qRT-PCR. Expression of Nrf2 protein was determined using western blotting. TUNEL assay was performed to evaluate cell apoptosis. Administration of obestatin significantly improved doxorubicin-induced dysfunction of left ventricular contractility function, moreover, resulted in upregulation of Mhrt and Nrf2 in failing myocardial tissue. Co-incubation of obestatin and doxorubicin in primary cardiomyocytes also enhanced Mhrt and Nrf2 expression as well as prevented cell apoptosis in comparison with doxorubicin only. Manipulation of cellular Mhrt by pcDNA-Mhrt or si-Mhrt transfection positively regulated Nrf2 expression in doxorubicin-incubated cardiomyocytes. Silencing Mhrt reversed cardioprotective effects of obestatin both in vivo and in vitro. Administration of obestatin attenuates doxorubicin-induced cardiac dysfunction via preservation of cardiomyocytes apoptosis in a Mhrt-Nrf2 dependent pathway.


Anatomic distribution of fluorodeoxyglucose-avid para-aortic lymph nodes in patients with cervical cancer.
Conformal treatment of para-aortic lymph nodes (PAN) in cervical cancer allows dose escalation and reduces normal tissue toxicity. Currently, data documenting the precise location of involved PAN are lacking. We define the spatial distribution of this high-risk nodal volume by analyzing fluorodeoxyglucose (FDG)-avid lymph nodes (LNs) on positron emission tomography/computed tomography (PET/CT) scans in patients with cervical cancer. We identified 72 PANs on pretreatment PET/CT of 30 patients with newly diagnosed stage IB-IVA cervical cancer treated with definitive chemoradiation. LNs were classified as left-lateral para-aortic (LPA), aortocaval (AC), or right paracaval (RPC). Distances from the LN center to the closest vessel and adjacent vertebral body were calculated. Using deformable image registration, nodes were mapped to a template computed tomogram to provide a visual impression of nodal frequencies and anatomic distribution. We identified 72 PET-positive para-aortic lymph nodes (37 LPA, 32 AC, 3 RPC). All RPC lymph nodes were in the inferior third of the para-aortic region. The mean distance from aorta for all lymph nodes was 8.3 mm (range, 3-17 mm), and from the inferior vena cava was 5.6 mm (range, 2-10 mm). Of the 72 lymph nodes, 60% were in the inferior third, 36% were in the middle third, and 4% were in the upper third of the para-aortic region. In all, 29 of 30 patients also had FDG-avid pelvic lymph nodes. A total of 96% of PET positive nodes were adjacent to the aorta; PET positive nodes to the right of the IVC were rare and were all located distally, within 3 cm of the aortic bifurcation. Our findings suggest that circumferential margins around the vessels do not accurately define the nodal region at risk. Instead, the anatomical extent of the nodal basin should be contoured on each axial image to provide optimal coverage of the para-aortic nodal compartment.


Metal-Organic Framework Glass Anode with an Exceptional Cycling-Induced Capacity Enhancement for Lithium-Ion Batteries.
Metal-organic frameworks (MOFs) hold great promise as high-energy anode materials for next-generation lithium-ion batteries (LIBs) due to their tunable chemistry, pore structure and abundant reaction sites. However, the pore structure of crystalline MOFs tends to collapse during lithium-ion insertion and extraction, and hence, their electrochemical performances are rather limited. As a critical breakthrough, a MOF glass anode for LIBs has been developed in the present work. In detail, it is fabricated by melt-quenching Cobalt-ZIF-62 (Co(Im)1.75 (bIm)0.25 ) to glass, and then by combining glass with carbon black and binder. The derived anode exhibits high lithium storage capacity (306 mAh g-1 after 1000 cycles at of 2 A g-1 ), outstanding cycling stability, and superior rate performance compared with the crystalline Cobalt-ZIF-62 and the amorphous one prepared by high-energy ball-milling. Importantly, it is found that the Li-ion storage capacity of the MOF glass anode continuously rises with charge-discharge cycling and even tripled after 1000 cycles. Combined spectroscopic and structural analyses, along with density functional theory calculations, reveal the origin of the cycling-induced enhancement of the performances of the MOF glass anode, that is, the increased distortion and local breakage of the CoN coordination bonds making the Li-ion intercalation sites more accessible.


Biochemical characterization of the human RAD51 protein. III. Modulation of DNA binding by adenosine nucleotides.
Adenosine nucleotides affect the ability of RecA small middle dotsingle-stranded DNA (ssDNA) nucleoprotein filaments to cooperatively assume and maintain an extended structure that facilitates DNA pairing during recombination. Here we have determined that ADP and ATP/ATPgammaS affect the DNA binding and aggregation properties of the human RecA homolog human RAD51 protein (hRAD51). These studies have revealed significant differences between hRAD51 and RecA. In the presence of ATPgammaS, RecA forms a stable complex with ssDNA, while the hRAD51 ssDNA complex is destabilized. Conversely, in the presence of ADP and ATP, the RecA ssDNA complex is unstable, while the hRAD51 ssDNA complex is stabilized. We identified two hRAD51 small middle dotssDNA binding forms by gel shift analysis, which were distinct from a well defined RecA small middle dotssDNA binding form. The available evidence suggests that a low molecular weight hRAD51 small middle dotssDNA binding form (hRAD51 small middle dotssDNA(low)) correlates with active ADP and ATP processing. A high molecular weight hRAD51 small middle dotssDNA aggregate (hRAD51 small middle dotssDNA(high)) appears to correlate with a form that fails to process ADP and ATP. Our data are consistent with the notion that hRAD51 is unable to appropriately coordinate ssDNA binding with adenosine nucleotide processing. These observations suggest that other factors may assist hRAD51 in order to mirror RecA recombinational function.


Morphological and structural characteristics of orthodontic mini-implants.
The purpose of this study was to investigate the geometric characteristics, composition, microstructure, and pullout strength of commercially available orthodontic mini-implants. The mini-implants used were AbsoAnchor®, Dual-Top™ JA, Spider Screws® K1, and Vector-TAS™. The geometric features were measured by optical microscopy. Surface texture and elemental composition were examined by scanning electron microscopy and energy dispersive X-ray microanalysis. Surface 3D roughness was estimated by optical profilometry, and pullout strength measured in artificial bone blocks with two bone densities. The AbsoAnchor® showed the highest intra-osseous surface area, followed by the Dual-Top™, Spider Screw®, and Vector-TAS™. The mini-implants were composed of a Ti6Al4V alloy. The Vector-TAS™ had the highest oxygen and phosphorus content with the most homogeneous surface texture. No significant differences were detected in amplitude surface roughness parameters (Sa, Sz) between the implants. However, differences existed in hybrid (Sdr, Sds) and functional (Sci) parameters. AbsoAnchor® achieved the highest pullout strength, followed by the Dual-Top™, Spider Screw®, and Vector-TAS™, with highest values in the high density group. The intra-osseous surface area of mini-implants showed a positive correlation with pullout strength, especially in the high density group. All the mini-implants tested were made of Ti6Al4V alloy. Significant differences were found in the surface area of the threaded parts. The significant differences documented in 3D surface roughness parameters (hybrid and functional) and pullout strength may anticipate variations in their clinical performance.


Bioimpedentiometry parameters used as indicators of frailty and malnutrition: association between G8 score and Phase angle (PHA) in elderly cancer patients.
Since the incidence of cancer increases with age, in older cancer patients important information may be missed without a Comprehensive Geriatric Assessment (CGA). On the other side, CGA is a time-consuming and complex instrument, so that Geriatric 8 (G8) has been proposed as a more feasible screening tool to identify patients who could benefit from a CGA evaluation. G8 consists of 8 questions (patient age + 7 items derived from the Mini Nutritional Assessment questionnaire). A G8 score ≤ 14 is considered associated with frailty and risk of malnutrition. Another screening test is Bioelectrical Impedance Analysis (Bioimpedentiometry, BIA), which enables to evaluate the nutritional status through a specific parameter known as Phase angle (PhA). This study is aimed at assessing the ability of G8 alone or in combination with PhA to detect elderly cancer patients at higher risk for malnutrition who cannot undergo immediate anticancer treatments. A total of 289 cancer patients (168 men and 121 women) aged ≥ 70 years old were enrolled and performed both G8 test, body mass index (BMI) and BIA assessments. A concurrent G8 score ≤ 14 and PhA < 5 defined subjects most exposed to the risk of malnutrition. An association between BMI and G8 (p < 0.001, OR 1.54) and a clinically significant relationship between G8 and PhA (p = 0.013) were observed. G8 can be used to identify patients at risk for malnutrition who would benefit from comprehensive CGA. The concurrent use of G8 and BIA presents a higher power in discriminating subjects at higher risk of malnutrition than a single test. This study suggests the need for routine assessment of nutritional status in cancer patients using combinations of methods, in order to implement strategies for individually-tailored care before starting any treatment.


Hyaluronidase: its effects on HI-6 dichloride and dimethanesulphonate pharmacokinetic profile in pigs.
Pigs were administered intramuscularly molar equivalents of HI-6 salts (HI-6 dichloride 10.71 mg/kg and HI-6 DMS 13.59 mg/kg) either with or without hyaluronidase (60 U/kg). Hyaluronidase is supposed to increase tissue permeability and diminishes discomfort caused by the intramuscular injection. Doses of HI-6 salts corresponded with standard HI-6 dichloride dose in one autoinjector (500 mg) and were recalculated for 1 kg of body weight. According to the results, both HI-6 salts applied in combination with hyaluronidase had increased tissue absorption and improved pharmacokinetic profile. The Cmax was significantly higher in case of HI-6 DMS plus hyaluronidase (29.6 ± 2.98 μg/ml) administration increase compared to HI-6 DMS (23.8 ± 3.04 μg/ml) and HI-6 dichloride (19.0 ± 0.93 μg/ml); both without hyaluronidase. Bioavailability calculated as AUCtotal (HI-6 DMS with hyaluronidase, 4,119 ± 647 min μg/ml) was also significantly higher compared to HI-6 DMS (2,259 ± 329 min μg/ml) and HI-6 dichloride (1,969 ± 254 min μg/ml); both without hyaluronidase. The results suggest that administration of HI-6 salt with higher solubility is the first step in the improvement of application strategy, but use some substances with spreading effect (hyaluronidase) may also leads to better absorption and better bioavailability. Improved bioavailability could to go hand in hand with increased effectiveness of therapy without the need of multiple autoinjector applications.


Neonatal infections with multidrug-resistant ESBL-producing E. cloacae and K. pneumoniae in Neonatal Units of two different Hospitals in Antananarivo, Madagascar.
We investigated the molecular mechanism of ß-lactam resistance in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterial strains isolated in neonatal units of different hospitals in Anatnanarivo, Madagascar. Bacteria were identified by standard biochemical methods, disc diffusion antibiograms and Etest. Resistance genes were sought by PCR. Strains were characterized by Rep-PCR (Diversilab), plasmid analysis and rep-typing. From April 2012 to March 2013, 29 ESBL-producing E. cloacae and 15 K. pneumoniae were isolated from blood culture (n = 32) or gastric samples (n = 12) performed at day 0 or 2 from 39/303 newborns suspected of early neonatal infection. These infants were treated with expanded spectrum cephalosporins, due to lack of carbapenems, leading to a high mortality rate (45 %). Isolates recovered were all, but 4, multidrug resistant, particularly to fluoroquinolones (FQ) except for 21 E. cloacae isolates. Isolates produced TEM-1 and CTX-M-15 ß-lactamases and their genes were located on several self-transferable plasmids of variable sizes sizes that could not be linked to a major plasmid incompatibility group. E. cloacae isolates belonged to 6 Rep-types among which two counted for 11 isolates each. The FQ resistant E. cloacae isolates belonged to one clone, whereas the FQ susceptible E. cloacae isolates belonged to four clones. The K. pneumoniae isolates belonged to 9 Rep-types among which one included five isolates. This study is the first molecular characterization of ESBL-producing isolates from neonatology units in Madagascar, a country with limited epidemiological data. It revealed an important multi-clonal dissemination of CTX-M-15-producing isolates reflecting both the high community carriage and the very early nosocomial contamination of the neonates.


Radiogenomics of lower-grade gliomas: machine learning-based MRI texture analysis for predicting 1p/19q codeletion status.
To evaluate the potential value of the machine learning (ML)-based MRI texture analysis for predicting 1p/19q codeletion status of lower-grade gliomas (LGG), using various state-of-the-art ML algorithms. For this retrospective study, 107 patients with LGG were included from a public database. Texture features were extracted from conventional T2-weighted and contrast-enhanced T1-weighted MRI images, using LIFEx software. Training and unseen validation splits were created using stratified 10-fold cross-validation technique along with minority over-sampling. Dimension reduction was done using collinearity analysis and feature selection (ReliefF). Classifications were done using adaptive boosting, k-nearest neighbours, naive Bayes, neural network, random forest, stochastic gradient descent, and support vector machine. Friedman test and pairwise post hoc analyses were used for comparison of classification performances based on the area under the curve (AUC). Overall, the predictive performance of the ML algorithms were statistically significantly different, χ2(6) = 26.7, p < 0.001. There was no statistically significant difference among the performance of the neural network, naive Bayes, support vector machine, random forest, and stochastic gradient descent, adjusted p > 0.05. The mean AUC and accuracy values of these five algorithms ranged from 0.769 to 0.869 and from 80.1 to 84%, respectively. The neural network had the highest mean rank with mean AUC and accuracy values of 0.869 and 83.8%, respectively. The ML-based MRI texture analysis might be a promising non-invasive technique for predicting the 1p/19q codeletion status of LGGs. Using this technique along with various ML algorithms, more than four-fifths of the LGGs can be correctly classified. • More than four-fifths of the lower-grade gliomas can be correctly classified with machine learning-based MRI texture analysis. Satisfying classification outcomes are not limited to a single algorithm. • A few-slice-based volumetric segmentation technique would be a valid approach, providing satisfactory predictive textural information and avoiding excessive segmentation duration in clinical practice. • Feature selection is sensitive to different patient data set samples so that each sampling leads to the selection of different feature subsets, which needs to be considered in future works.


Development of a computational model for acute ischemic stroke recanalization through cyclic aspiration.
Acute ischemic stroke (AIS), the result of embolic occlusion of a cerebral artery, is responsible for 87% of the 6.5 million stroke-related deaths each year. Despite improvements from first-generation thrombectomy devices for treating AIS, 80% of eligible stroke patients will either die or suffer a major disability. In order to maximize the number of patients with good outcomes, new AIS therapies need to be developed to achieve complete reperfusion on the first pass. One such therapy that has shown promise experimentally is the application of cyclic aspiration pressure, which led to higher recanalization rates at lower pressure magnitudes. In order to investigate AIS and cyclic aspiration recanalization, an improved computational modeling framework was developed, combining a viscoelastic thromboembolus model with a cohesive zone (CZ) model for the thromboembolus-artery interface. The model was first validated against experimental displacement data of a cyclically aspirated thromboembolus analog. The CZ model parameters, including the addition of a damage accumulation model, were then investigated computationally to determine their individual effects on the thromboembolus and CZ behavior. The relaxation time and the damage model critical opening length were shown to have the greatest effect on the CZ opening and led to increased displacement that accumulated with repeated loading. Additional simulations were performed with parameters relevant to AIS including internal carotid artery dimensions and thromboemboli mechanical properties. In these AIS cases, more upstream CZ opening was observed compared to the thromboembolus analog cases and greater displacement was achieved with the lower-frequency aspiration (0.5 vs 1 Hz).


[Role of vitamin K antagonists from a hepatologist's point of view].
Vitamin K antagonists are often used as oral anticoagulants for primary and secondary prevention of thromboembolic events. Vitamin K antagonists induce an anticoagulant effect by interfering with the vitamin K metabolism in the liver. Well-known complications are bleeding events and skin necrosis. Recent data indicate increasing numbers of cases with hepatic complications due to vitamin K antagonists ranging from mild hepatopathy to acute liver failure with high mortality. Hepatotoxicity is usually developed after a few months of latency, which is associated with unspecific symptoms, jaundice, elevated transaminase levels as well as cholestatic enzymes. Hepatotoxicity due to vitamin K antagonists is seldom; however, it should be considered in cases of elevated liver enzymes. In this case coumarin therapy should be discontinued. Caution is needed when changing to another coumarin derivative because cross-reactivity has been described.


Rapid simultaneous removal of nitrogen and phosphorous by a novel isolated Pseudomonas mendocina SCZ-2.
Nitrogen (N) and phosphorous (P) removal by a single bacterium could improve the biological reaction efficiency and reduce the operating cost and complexity in wastewater treatment plants (WWTPs). Here, an isolated strain was identified as Pseudomonas mendocina SCZ-2 and showed high performance of heterotrophic nitrification (HN) and aerobic denitrification (AD) without intermediate accumulation. During the AD process, the nitrate removal efficiency and rate reached a maximum of 100% and 47.70 mg/L/h, respectively, under optimal conditions of sodium citrate as carbon source, a carbon-to-nitrogen ratio of 10, a temperature of 35 °C, and shaking a speed of 200 rpm. Most importantly, the strain SCZ-2 could rapidly and simultaneously eliminate N and P with maximum NH4+-N, NO3--N, NO2--N, and PO43--P removal rates of 14.38, 17.77, 20.13 mg N/L/h, and 2.93 mg P/L/h, respectively. Both the N and P degradation curves matched well with the modified Gompertz model. Moreover, the amplification results of functional genes, whole genome sequencing, and enzyme activity tests provided theoretical support for simultaneous N and P removal pathways. This study deepens our understanding of the role of HN-AD bacteria and provides more options for simultaneous N and P removal from actual sewage.


P2-proline-derived inhibitors of calpain I.
The syntheses and biological activities of a series of calpain I inhibitors, derived from D- and L-Pro, are described.


Reducing the Misinformation Effect Through Initial Testing: Take Two Tests and Recall Me in the Morning?
Initial retrieval of an event can reduce people's susceptibility to misinformation. We explored whether protective effects of initial testing could be obtained on final free recall and source-monitoring tests. After studying six household scenes (e.g., a bathroom), participants attempted to recall items from the scenes zero, one, or two times. Immediately or after a 48-hour delay, non-presented items (e.g., soap and toothbrush) were exposed zero, one, or four times through a social contagion manipulation in which participants reviewed sets of recall tests ostensibly provided by other participants. A protective effect of testing emerged on a final free recall test following the delay and on a final source-memory test regardless of delay. Taking two initial tests did not increase these protective effects. Determining whether initial testing will have protective (versus harmful) effects on memory has important practical implications for interviewing eyewitnesses.


PSMA hybrid imaging in prostate cancer - current applications and perspectives.
Prostate cancer (PCa) is the most common malignancy in men and the second most common tumor-associated cause of death in the male population in Germany. Prostate-specific membrane antigen (PSMA)-targeted hybrid imaging using positron emission tomography (PET) in combination with CT or MRI represents a comparably new method that gained increasing importance in the diagnostic process of PCa in recent years. Current applications of PSMA hybrid imaging were summarized according to the German and European guidelines on PCa. New developments were elaborated based on a literature review of PubMed conducted in 10/22. PSMA-PET/CT demonstrated higher detection rates for metastases in high-risk PCa and recurrent PCa after primary therapy than established imaging methods (CT, MRI, and bone scan). Despite promising results from prospective trials in both scenarios and substantial influence on clinical decision making, data regarding the influence of PSMA-PET on PCa-specific and overall survival are still lacking. Hence, PSMA PET/CT is recommended with a "weak" strength rating in most situations. However, its importance in new treatment options like metastasis-directed therapy or PSMA-radioligand therapy expands the scope of PSMA-PET in the clinical routine. PSMA-targeting hybrid imaging represents the most sensitive diagnostic test in several stages of PCa and allows the development of new treatment strategies. Prospective studies are needed to evaluate the influence of PSMA-PET on patient survival. · PSMA-PET/CT is superior to conventional imaging in the primary staging of high-risk prostate cancer.. · PSMA hybrid imaging can detect metastases in patients with biochemical recurrence at low PSA values.. · Clinical decision making is frequently influenced by results of PSMA-PET/CT.. · Koehler D, Berliner C, Shenas F et al. PSMA hybrid imaging in prostate cancer - current applications and perspectives. Fortschr Röntgenstr 2023; 195: 1001 - 1008.


Pharyngocutaneous fistula: the incidence and the risk factors.
A pharyngocutaneous fistula is the most common complication following laryngectomy. A wide range of potential risk factors has been suggested. The purpose of this study was to determine the incidence and risk factors for the fistula at the Department of Otorhinolaryngology and Head and Neck Surgery in Ljubljana, Slovenia between 2007 and 2012. Charts from patients treated for head and neck cancer by laryngectomy were retrospectively reviewed. Comprehensive clinicopathologic data were collected including potential risk factors related to the patient, disease, surgery and postoperative period. The patients were categorised into the group with the fistula (a study group) and without it (a control group). The incidence of the fistula was calculated and the groups were statistically compared according to potential risk factors using the Chi square test, Fisher exact test, T test, Mann-Whitney U test and binary logistic regression analysis. Hundred fifty-eight patients were included. The incidence of the fistula was 30.4 %. In the primary laryngectomy group the incidence was 22.6 %, whereas in the salvage laryngectomy group 44.6 % (p = 0.006). The independent predictors for the fistula were history of head and neck cancer (p = 0.001), invasion of piriform sinus (p = 0.020) and surgical wound infection (p < 0.001). The timing of surgical wound infection could be of some importance. In the PCF group, it started on the 5th postoperative day, whereas in the control group on the 7th postoperative day (p = 0.063). Decreasing the rate of surgical wound infection could diminish the fistula rate.


Olfactory bulbectomy impairs the rat's radial-maze behavior.
Previous studies had shown that transection of the lateral olfactory tracts and lesions of the septohippocampal system were similar in the deficits they engendered in nest building and food piling or hoarding by hamsters. The present investigation asked whether olfactory lesions would also produce deficits in radial-maze behavior like those associated with septo-hippocampal lesions. Radical olfactory bulbectomy led to a marked deterioration in preoperatively trained behavior in an 8-arm radial maze. The behavioral changes resembled those resulting from septo-hippocampal lesions in three ways: (1) There were fewer choices of adjacent arms and more choices of more distant arms. (2) Choice accuracy as a function of successive choices within a trial declined more rapidly. (3) The probability of repeating choice sequences was abnormally high. Earlier studies had shown that the rat does not require olfactory cues to perform efficiently in radial mazes. It therefore seems likely that the deficits described here resulted from the disruption of interconnections between the olfactory and septo-hippocampal systems rather than from the loss of olfactory sensitivity.


Mounting and brief noncontact exposure of males to receptive females facilitate reflexive erection in rats, even after hypogastric nerve section.
In three experiments, reflexive erection in male rats was facilitated by housing the males for 2 min with inaccessible sexually receptive females. In Experiment 1, males were sexually naive or experienced and received two reflexive erection tests, 1 week apart, immediately after the males were exposed to receptive females, to unreceptive females, or to no females (n = 8 per group). In both tests, experienced males exposed to estrous females had the shortest reflexive erection latencies; in Test 1 the differences among groups were of borderline significance (p = 0.057), but in Test 2 the differences among groups were highly reliable (p<0.01). Further analysis indicated that only experienced males exposed to receptive females were significantly different from other groups. In Experiment 2, sexually experienced males (n = 11) received four reflexive erection tests: after being with no female, and 0, 5, or 10 min after exposure to estrous females. As the interval between exposure and test increased, the males had progressively shorter erection latencies (p<0.01) and more intense glans erections (p<0.03). Experiments 1 and 2 may be viewed as demonstrating the psychogenic facilitation of reflexive erections. In Experiment 3, males underwent sham surgery (sham, n = 10) or bilateral transection of the hypogastric nerves (HgNx, n = 10), which are conventionally viewed as mediating psychogenic erection. After males mounted a receptive female for 5 min without intromission or had 2 min of non-contact exposure to receptive females, the males had shorter erection latencies (p<0.001) and more erections (p<0.02). These facilitative effects of pretest stimulation were unaffected by HgN transection. During copulation tests, HgNx males had longer ejaculation latencies (p<0.05) and lower intromission ratios (p<0.05), possible signs of impaired erectile function. However, in Experiment 4, other males were tested twice for reflexive erection and copulation after sham (n = 8) or HgNx (n = 9) surgery, and there were no significant effects of surgery on reflexive erection or copulatory behavior. Collectively, these experiments indicate (a) that brief noncontact exposure of sexually experienced males to estrous females facilitates reflexive erection, (b) that this facilitation increases for at least 10 min after the females are removed, and (c) that the hypogastric nerves do not mediate these facilitative effects. The evidence for a role for the HgN in copulation was inconclusive.


Research in orthokeratology. Part VII: examination of techniques, procedures and control.
Since contact lenses are responsible for producing corneal change it is essential to rigorously examine for variables involved. The need to control corneal change further dictates that fitting procedures or techniques should also be critically evaluated. Given in this first of a two part series is a background discussion of contact lens prescribing characteristics and resultant data collected during an orthokeratology study. Specifically examined were the effects of the base curve-cornea relationship, lens position and temporal factors. Though each was noticed to be involved in the results obtained, their failure to account for all changes observed suggest that other mechanisms need be considered.


Pediatric assessment in the home.
Caring for children holistically in the home can be challenging and is dependent on working closely with families. This article identifies the four roles a nurse performs when conducting a home pediatric assessment. The Home Risk Assessment Tools presented assist nurses in evaluating a child's physical and psychosocial needs.


[Toxicity of immune checkpoints inhibitors].
Anti-tumoral immunotherapy is currently the basis of a profound modification of therapeutic concepts in oncology, in particular since the arrival of immune checkpoint inhibitors (ICI). In addition to their efficacy profile, these immune-targeted agents also generate adverse events. With the increasing use of ICI for a growing number of tumor types, awareness of immunotherapy-related adverse events is essential to ensure prompt diagnosis and effective management of these potentially serious adverse events. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (irAEs), which resemble autoimmune disease. Though severe irAEs remain rare, they can be fatal if not diagnosed and treated in an appropriate manner. Additional studies are needed to better understand the clinical characteristics and chronology of these adverse effects and to clarify their pathophysiological mechanisms.


Fullerol Nanocatalysis and Trimodal Surface Plasmon Resonance for the Determination of Isocarbophos.
Fullerol (C60OH) has been shown to catalyze the trisodium citrate (TSC)-silver nitrate reaction to generate Ag nanoparticles (AgNPs). These AgNPs exhibit significant nanoplasmic surface-enhanced Raman scattering (SERS), resonance Rayleigh scattering (RRS), and absorption (Abs). When an aptamer (Apt) adsorbs on the C60OH surface, catalysis is inhibited, and the intensities of SERS, RRS, and Abs decrease. In the presence of isocarbophos (IPS), Apt forms a stable complex (Apt-IPS) and releases C60OH. As a result, SERS, RRS, and Abs intensities increase with increasing IPS concentration. Accordingly, a new SERS, RRS, and Abs trimodal method using Apt-labeled fullerol was established for the determination of IPS. Of the three spectral methods, SERS was the most sensitive, while the Abs method was the most cost-effective.


Dental age estimation in children affected by juvenile rheumatoid arthritis.
Dental root calcification has proven to be a reliable biological evidence to estimate chronological age of children. The development of structures usually examined in the age estimation forensic practice (e.g. skeleton, teeth) is supposed to be influenced by diseases and nutritional, environmental, ethnic, and ultimately even socioeconomic factors. This research aims to study the age estimation in children affected by juvenile rheumatoid arthritis (JRA) with and without steroids treatment and compared with healthy subjects. MATERIAL AND METHODS: Dental age estimations based on 752 OPGs, 420 girls and 332 boys, aged from 3.3 to 15.99 years, were provided by applying Demirjian and Willems' original methods. Of the whole sample, 103 individuals were affected by JRA and 40 received a continuous corticosteroid therapy, over 1 year long. CONCLUSIONS: Willems' and Demirjian's original methods, as methods commonly applied to estimate age for sub-adults with unremarkable medical history, can be used for medico-legal purposes to children affected by JRA. Willems' method tended to underestimate age while Demirjian's method resulted to be prone to overestimation for both healthy and JRA-affected children. JRA showed to have no influence on root calcification process even in children that received steroid treatment for 1 year or longer.


Confocal scanning laser microscope images of hippocampal neurons intracellularly labeled with biocytin.
We have assessed the properties and usefulness of confocal scanning laser microscopy in the reflection mode for the study of neuronal morphology. In this mode, the confocal microscope detects the light reflected off the specimen as opposed to the light emitted by a fluorescent label. Neurons in slices of rat hippocampus were filled with biocytin and reacted sequentially with avidin-horseradish peroxidase and nickel-intensified diaminobenzidine (DAB/Ni). In all parts of the neuron the DAB/Ni reaction product produced a strong reflection signal in the confocal microscope. The stereo images revealed aspects of three-dimensional hippocampal cell morphology such as the conical shape of the dendritic fields and a characteristic branching pattern of the axon. Labelling neurons intracellularly is an established technique for identifying physiologically-characterized neurons. Recently, confocal microscopy has become a powerful method for examining the three-dimensional morphology of biological specimens. The resulting images in this paper show that reflection-mode confocal microscopy provides an excellent representation of the filled neurons in three dimensions and presents an opportunity for correlative electrophysiological and morphological studies and extension to the electron-microscopic level.


Indian and United States paramedic students: comparison of examination performance for the American Heart Association Advanced Cardiovascular Life Support (ACLS) training.
The American Heart Association (AHA) Advanced Cardiovascular Life Support (ACLS) course is taught worldwide. The ACLS course is designed for consistency, regardless of location; to our knowledge, no previous study has compared the cognitive performance of international ACLS students to those in the United States (US). As international health educational initiatives continue to expand, an assessment of their efficacy is essential. This study assesses the AHA ACLS curriculum in an international setting by comparing performance of a cohort of US and Indian paramedic students. First-year paramedic students at the Emergency Management and Research Institute, Hyderabad, India, and a cohort of first-year paramedic students from the United States comprised the study population. All study participants had successfully completed the standard 2-day ACLS course, taught in English. Each student was given a 40-question standardized AHA multiple-choice examination. Examination performance was calculated and compared for statistical significance. There were 117 Indian paramedic students and 43 US paramedic students enrolled in the study. The average score was 86% (± 11%) for the Indian students and 87% (± 6%) for the US students. The difference between the average examination scores was not statistically significant in an independent means t-test (p=0.508) and a Wilcoxon test (p=0.242). Indian paramedic students demonstrated excellent ACLS cognitive comprehension and performed at a level equivalent to their US counterparts on an AHA ACLS written examination. Based on the study results, the AHA ACLS course proved effective in an international setting despite being taught in a non-native language.


Acute changes in peritoneal morphology and transport properties with infectious peritonitis and mechanical injury.
Peritoneal clearance studies were performed in rats undergoing acute peritoneal dialysis. Some of these animals were then exposed to laparotomy and mechanical drying of the peritoneum. Peritoneal clearance studies were repeated at intervals up to 11 days. Another group of rats was placed on daily peritoneal dialysis and allowed to spontaneously develop peritonitis which was not treated. These rats underwent peritoneal transport studies at differing durations of infection. In all groups, animals were sacrificed at the time of the last transport studies for morphological assessment of the peritoneum by light microscopy, scanning electron microscopy, and transmission electron microscopy. The results showed similar decreases in drainage volume and increases in glucose absorption and protein losses with both infection and drying. Both types of injury resulted in extensive mesothelial structural changes. While drying caused mainly denudation of the mesothelial surface, infectious peritonitis was associated with separation of mesothelial cells, and the appearance of numerous white blood cells between and on mesothelial cells. Exposure to peritoneal dialysis alone had no obvious effects on anatomy. Although changes in the peritoneal microcirculation and deeper structures cannot be excluded as contributing to peritoneal transport alterations, the findings suggest that alterations of mesothelium might explain some of the changes in peritoneal transport properties under the conditions of these studies.


Functional activity characteristics of individuals with shoulder dysfunctions.
Shoulder-related dysfunction affects individuals' ability to function independently and thus decreases quality of life. Functional task assessment is a key concern for a clinician in diagnostic assessment, outcome measurement, and planning of treatment programs. The purpose of this study was to test the reliability of the FASTRAK 3-dimensional (3-D) motion analysis and surface electromyography (sEMG) systems to analyze 3-D shoulder complex movements during functional tasks and compare motion patterns between subjects with and without shoulder dysfunctions (SDs).For the test, sEMG and 3-D motion analysis systems were used to characterize the functional tasks. Twenty-five asymptomatic male subjects and 21 male subjects with right shoulder disorders performed four functional tasks which involved arm reaching and raising activities with their dominant arms. Reliability was estimated by the intraclass correlation coefficient (ICC). Motion pattern was compared between two groups using mixed analysis of variances (ANOVAs). Shoulder complex kinematics and associated muscular activities during functional tasks were reliably quantified (ICC=0.83-0.99) from the means of three trials. Relative to the group without SDs, the group with SDs showed significant alteration in shoulder complex kinematics (3 degrees -40 degrees ) and associated muscular activities (3-10% maximum). Scapular tipping, scapular elevation, upper trapezius muscle function, and serratus anterior muscle function may have implications in the rehabilitation of patients with SDs.


Structured reflection on shared decision making.
Shared decision making (SDM), whereby patients and clinicians work collaboratively to make health care decisions, brings multiple benefits. It has, however, been slow to integrate into clinical practice. There are some examples of SDM being embedded and evaluated within medical undergraduate curricula but, despite role models being important in promoting students' patient-centred attitudes, these examples do not involve students reflecting on clinicians' use of SDM in practice. We undertook a qualitative evaluation of a small group educational intervention. A key element was the students' use of a structured reflective template, drawing on the SHARE (seek, help, assess, reach, evaluate) SDM tool, to analyse examples of clinicians using SDM in practice critically. We undertook a thematic analysis of students' completed templates and evaluated their engagement with the SHARE tool. A total of 44 templates were analysed. Four main themes were identified, including new learning about SDM, noticing and deconstructing SDM, participants' responses to SDM and struggles in learning. Students were positive about SHARE and used it to critique experiences and suggest specific ways that clinicians could have improved SDM. A structured training intervention that promotes critical reflection on clinical role models can help to shift undergraduate medical students' understanding of, and attitudes towards, SDM. The ethical arguments for SDM, evidence for its benefits and the alignment of SDM with participants' own core values appeared to help achieve student 'buy in'. Students struggled with notions of power, risk and time constraints, and empathised with both patients and clinicians. They highlighted the scarcity of SDM in practice.


Fibrin biomatrix-conjugated platelet-derived growth factor AB accelerates wound healing in severe thermal injury.
Controlled delivery of growth factors from biodegradable biomatrices could accelerate and improve impaired wound healing. The study aim was to determine whether platelet-derived growth factor AB (PDGF.AB) with a transglutaminase (TG) crosslinking substrate site released from a fibrin biomatrix improves wound healing in severe thermal injury. The binding and release kinetics of TG-PDGF.AB were determined in vitro. Third-degree contact burns (dorsum of Yorkshire pigs) underwent epifascial necrosectomy 24 h post-burn. Wound sites were covered with autologous meshed (3:1) split-thickness skin autografts and either secured with staples or attached with sprayed fibrin sealant (FS; n = 8/group). TG-PDGF.AB binds to the fibrin biomatrix using the TG activity of factor XIIIa, and is subsequently released through enzymatic cleavage. Three doses of TG-PDGF.AB in FS (100 ng, 1 µg and 11 µg/ml FS) were tested. TG-PDGF.AB was bound to the fibrin biomatrix as evidenced by western blot analysis and subsequently released by enzymatic cleavage. A significantly accelerated and improved wound healing was achieved using sprayed FS containing TG-PDGF.AB compared to staples alone. Low concentrations (100 ng-1 µg TG-PDGF.AB/ml final FS clot) demonstrated to be sufficient to attain a nearly complete closure of mesh interstices 14 days after grafting. TG-PDGF.AB incorporated in FS via a specific binding technology was shown to be effective in grafted third-degree burn wounds. The adhesive properties of the fibrin matrix in conjunction with the prolonged growth factor stimulus enabled by this binding technology could be favourable in many pathological situations associated with wound-healing disturbances. Copyright © 2013 John Wiley & Sons, Ltd.


Soil erosion assessment in the Amazon basin in the last 60 years of deforestation.
Anthropic activities in the Amazon basin have been compromising the environmental sustainability of this complex biome. The main economic activities depend on the deforestation of the rainforest for pasture cattle ranching and agriculture. This study analyzes soil erosion to understand how deforestation has impacted the Amazon basin in this context, using three land-use temporal maps (1960, 1990, 2019) through the revised universal soil loss equation (RUSLE). Our results point to a significant influence of deforestation due to the expansion of agricultural and livestock activities on soil erosion rates in the Amazon Basin. The average soil erosion rate has increased by more than 600% between 1960 and 2019, ranging from 0.015 Mg ha-1 year-1 to 0.117 Mg ha-1 year-1. During this period, deforestation of the Amazon rainforest was approximately 7% (411,857 km2), clearly the leading cause of this increase in soil erosion, especially between 1990 and 2019. The south and southeast regions are the most impacted by increasing soil erosion, in which deforestation was accelerated for expanding agriculture and livestock activities, mainly in the sub-basins of the Madeira, Solimões, Xingu, and Tapajós that present soil erosion increases of 390%, 350%, 280%, and 240%, respectively. The sub-basins with the highest sediment delivery rate (SDR) are under the influence of the Andes, highlighting Solimões (27%), Madeira (13%), and Negro (6%) due to the increase in the soil erosion rate increase in these sub-basins.


Removal of Cu(II) from wastewater by using mechanochemically activated carbonate-based tailings through chemical precipitation.
This work explored the feasibility of utilizing the copper tailings (CT) for removing copper from the waste mine water based on the mechanochemical activation. Batch experiments were performed to evaluate the influences of various experimental parameters like the dosage of CT, reaction time, initial concentration of Cu, and anion species. By cogriding copper solution with CT in the stirred mill (mechanochemical activation), over 99.5% of copper was removed and the residual copper concentration in the solution was less than 0.5 mg/L, reaching the discharge limit. This reaction was a chemical precipitation process. The calcite of CT played a major role in precipitating copper and had a better removal effect on copper in the copper sulfate solution than copper nitrate solution. For copper sulfate solution, the copper deposit was mainly posnjakite (Cu4(SO4)(OH)6·H2O). In the copper nitrate solution, the copper sediment might consist mainly of basic copper nitrate. The stability of the two reaction products was measured by leaching test. The result showed that the sediment obtained by this method was relatively stable and was not hazardous wastes.


Joint spectral quantification of MR spectroscopic imaging using linear tangent space alignment-based manifold learning.
To develop a manifold learning-based method that leverages the intrinsic low-dimensional structure of MR Spectroscopic Imaging (MRSI) signals for joint spectral quantification. A linear tangent space alignment (LTSA) model was proposed to represent MRSI signals. In the proposed model, the signals of each metabolite were represented using a subspace model and the local coordinates of the subspaces were aligned to the global coordinates of the underlying low-dimensional manifold via linear transform. With the basis functions of the subspaces predetermined via quantum mechanics simulations, the global coordinates and the matrices for the local-to-global coordinate alignment were estimated by fitting the proposed LTSA model to noisy MRSI data with a spatial smoothness constraint on the global coordinates and a sparsity constraint on the matrices. The performance of the proposed method was validated using numerical simulation data and in vivo proton-MRSI experimental data acquired on healthy volunteers at 3T. The results of the proposed method were compared with the QUEST method and the subspace-based method. In all the compared cases, the proposed method achieved superior performance over the QUEST and the subspace-based methods both qualitatively in terms of noise and artifacts in the estimated metabolite concentration maps, and quantitatively in terms of spectral quantification accuracy measured by normalized root mean square errors. Joint spectral quantification using linear tangent space alignment-based manifold learning improves the accuracy of MRSI spectral quantification.


Change in cardiac myocyte size distribution in aortic-constricted neonatal rats.
Regional changes in cardiac myocyte size and population distribution were examined in Sprague Dawley rats receiving an abdominal aortic constriction at five days of age. At specific time intervals post-constriction, hearts were recovered from constricted animals and weight-matched controls and isolated myocytes were obtained from right and left ventricles using retrograde coronary perfusion with collagenase. Cell volume and cardiac myocyte population distribution curves were determined using a Coulter Channelyzer system. Cell length was measured directly using a Bioquant Image Analysis system. Myocyte cross-sectional area was calculated from cell volume/length. By three months of age, heart weight and heart weight-body weight ratio in constricted animals had increased by approximately 115% (p less than 0.001) in females and 85% (p less than 0.001) in males compared to controls. Between 15 and 90 days of age, the growth response, as indicated by increased cell volume, was approximately 4x greater in constricted females and 2.5x greater in constricted males compared to corresponding controls. This increase was manifested by a shift in the mean size of the myocyte population to the right and a substantial widening of the distribution. Most of the enlargement was due to increased cross-sectional area, with only a moderate contribution from increased cell length. Significant increases in size were seen in both left and right ventricles. By three months of age, a significant interaction was apparent between aortic constriction and sex. The capacity for hypertrophy was greater in the smaller myocytes in female rats of similar age compared to males. The final degree of hypertrophy was similar for male and female rats, possibly indicating a critical upper limit in cell size for cardiac myocytes.


Serum metabolite profiling of ST-segment elevation myocardial infarction using liquid chromatography quadrupole time-of-flight mass spectrometry.
ST segment elevation myocardial infarction (STEMI) is one of the most common global causes of cardiovascular disease-related death. Several metabolites may change during STEMI. Hence, analysis of metabolites in body fluid may be considered as a rapid and accurate test for initial diagnosis. This study has therefore attempted to determine the variation in metabolites identified in the serum of STEMI patients (n = 20) and 15 controls. Samples collected from the Cardiology Department, Medical Faculty, Ataturk University, were extracted by liquid-liquid extraction and analysed using liquid chromatography quadrupole time-of-flight mass spectrometry. The METLIN database was used for the identification and characterization of metabolites. According to Q-TOF/MS measurements, 231 m/z values, which were significantly different between groups (P < 0.01 and fold analysis >1.5) were detected. Metabolite identification was achieved via the Human Metabolome database. According to the multivariate data analysis, leucine, isoleucine, l-proline, l-alanine, glycine, fumaric acid, citrate, succinate and carnitine levels were decreased, whereas levels of propionic acid, maleic acid, butyric acid, urea, oleic acid, palmitic acid, lysoPC [18:2(9Z)], glycerol, phoshpatidylethanolamine, caffeine and l-lactic acid were increased in STEMI patients compared with controls. In conclusion, malonic acid, maleic acid, fumaric acid and palmitic acid can be used as biomarkers for early risk stratification of patients with STEMI.


Macular hole closure patterns: an updated classification.
The classification of macular hole closure patterns (MHCPs) currently relies on time domain OCT allowing only "open" and "closed" statuses or is based on inner foveal contour shape. Both classification types give no information on retinal layer reconstitution. Novel sophisticated surgical techniques lead to previously unknown MHCPs, outdating existing classifications and urging new ones. The purpose of the present study is to introduce a new classification allowing proper description of all MHCPs resulting from newer surgeries and based on the restoration of retinal layers. Retrospective analysis of patients undergoing MH surgery with five different surgical techniques was performed. MHCPs were classified according to spectral domain optical coherence tomography (SD-OCT). Type 0: open MH (0A: flat margin, 0B: elevated, 0C: oedematous); type 1: closed MHs (1A: reconstitution all retinal layers; 1B interruption of the external layers; 1C interruption of internal layers); type 2: MH closed with autologous or heterologous filling tissue interrupting the normal foveal layered anatomy (2A: filling tissue through all layers; 2B reconstitution of normal inner retinal layers; 2C reconstitution of normal outer retinal layers; 2D H-shaped bridging of filling tissue). Closure rate was 95.2% (241/253). Surgical technique and vision correlated to closure pattern (p < 0.001). Type 1 MHCPs had the best post-operative visual acuity (VA) compared with type 2 and type 0 (p < 0.001). MHCPs 1A and 1C performed better than all others. MHCP at months 1 and 3 changed in 42/254 (16.5%) and remained stable in 212/254 (83.5%). Improvement in vision was higher in eyes with shifting closure pattern (0.57 ± 0.33 vs 0.51 ± 0.48 logMAR; p 0.021). MHCP classification based on retinal layer restoration properly comprises post-operative anatomic morphologies. MHCPs correlate the surgical technique and post-operative visual outcomes.


Training needs in adolescent medicine of practising doctors: a Swiss national survey of six disciplines.
To assess and compare the training needs in adolescent medicine of doctors within 6 specialties as a basis for the development of pre/postgraduate and continuing medical education (CME) training curricula. Cross-sectional postal survey. Switzerland. National, representative, random sample of 1857 practising doctors in 6 disciplines (general practitioners, paediatricians, gynaecologists, internists, psychiatrists, child psychiatrists) registered with the Swiss Medical Association. Perceived importance of and training interest in 35 topics related to adolescent medicine listed in a self-administered, anonymous questionnaire. A total of 1367 questionnaires were returned, representing a response rate of 73.9%. Clear interest in adolescent medicine was reported by 62.1% of respondents. Topics perceived to be the most important in everyday practice were functional symptoms (71.4%), acne (67.1%), obesity (64.6%), depression-anxiety (68.1%) and communication with adolescents (61.7%). Differences between disciplines were especially marked for gynaecologists, who expressed interest almost exclusively in medical topics specific to their field. In contrast, other disciplines commonly reported a keen interest in psychosocial problems. Accordingly, interest in further training was expressed mostly for functional symptoms (62.4%), eating disorders (56.3%), depression-anxiety (53.7%) and obesity (52.6%). Issues related to injury prevention, chronic disease and confidentiality were rated as low priorities. Regardless of discipline, Swiss primary care doctors expressed a strong interest in adolescent medicine. Continuing medical education courses should include both interdisciplinary courses and discipline-specific sessions. Further training should address epidemiological and legal/ethical issues (e.g. injury prevention, confidentiality, impact of chronic conditions).


Pluripotent stem cell models of Shwachman-Diamond syndrome reveal a common mechanism for pancreatic and hematopoietic dysfunction.
Shwachman-Diamond syndrome (SDS), a rare autosomal-recessive disorder characterized by exocrine pancreatic insufficiency and hematopoietic dysfunction, is caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene. We created human pluripotent stem cell models of SDS through knockdown of SBDS in human embryonic stem cells (hESCs) and generation of induced pluripotent stem cell (iPSC) lines from two patients with SDS. SBDS-deficient hESCs and iPSCs manifest deficits in exocrine pancreatic and hematopoietic differentiation in vitro, enhanced apoptosis, and elevated protease levels in culture supernatants, which could be reversed by restoring SBDS protein expression through transgene rescue or by supplementing culture media with protease inhibitors. Protease-mediated autodigestion provides a mechanistic link between the pancreatic and hematopoietic phenotypes in SDS, highlighting the utility of hESCs and iPSCs in obtaining novel insights into human disease.


Efficacy and side effects of the regional arterial infusion of anti-cancer drugs combined with direct hemoperfusion in malignancies of the urinary tract.
Regional arterial infusion of high doses of anti-cancer drugs combined with direct hemoperfusion was done in 12 patients with malignancies of the urinary tract. The perfuser contained 130 gm. activated charcoal, which was coated with cellulose. General toxicity caused by escape of the drug from the tumor area was prevented by adsorption within activated charcoal. The capacity of activated charcoal to adsorb doxorubicin hydrochloride was excellent, as determined by measurements of plasma concentration. With this method, objective tumor reduction was noted in 84 per cent of the patients with prostatic or bladder carcinoma, although results were disappointing in patients with renal cell carcinoma.


Chiral phosphine-catalyzed enantioselective construction of gamma-butenolides through substitution of Morita-Baylis-Hillman acetates with 2-trimethylsilyloxy furan.
Chiral multifunctional phosphine (R)-N-(2'-diphenylphosphanyl-[1,1']binaphthalenyl-2-yl)methanesulfonamide L2 or (R)-N-(2'-diphenylphosphanyl-[1,1']binaphthalenyl-2-yl)acetamide L3 is an efficient catalyst in the allylic substitutions of MBH acetates 1 with 2-trimethylsilyloxy furan 2 to provide gamma-butenolides 3 in good to excellent yields and enantiomeric excesses in the presence of water.


Behavior of repolarization variables during exercise test in the athlete's heart.
T peak-T end, QT peak/QT ratio and T peak-T end/QT ratio are markers able to test myocardial repolarization homogeneity, their increase has been related to a higher risk of ventricular tachyarrhythmias. These parameters have not yet been studied in left ventricular hypertrophy due to training. Aim of the research was to test the behavior of these variables in the athlete's heart during exercise. We examined 70 athletes, all males, divided into two groups according to the absence or the presence of a left ventricular mass index over 49 g/m(2.7) and a control group composed of 35 healthy, untrained males. All study participants underwent electrocardiogram at rest, transthoracic echocardiogram, and ergometric test. Repolarization markers (QT, corrected QT, QT dispersion, T peak-T end, QT peak/QT, T peak-T end/QT) were calculated at rest, at peak exercise and during recovery. There was no statistically significant difference among the groups regarding all the parameters studied, except for corrected QT at rest between athletes with left ventricular hypertrophy and control group. The behavior of repolarization markers during exercise was not dissimilar in the three groups. Athlete's heart is not associated to any alteration in ventricular repolarization homogeneity, neither at rest nor during physical activity nor during recovery. Training-induced left ventricular hypertrophy does not affect relationship QT parameters/RR interval.


Prognostic significance of left ventricular diastolic dysfunction in patients with left ventricular hypertrophy and systemic hypertension (the LIFE Study).
Patients with hypertension and left ventricular (LV) hypertrophy commonly have impaired diastolic filling. However, it remains unknown whether changes in LV diastolic filling variables are associated with cardiovascular morbidity and mortality. In this study, 778 patients with hypertension with electrocardiographic LV hypertrophy who underwent echocardiography at baseline and annually thereafter during randomized losartan- or atenolol-based antihypertensive treatment were followed for a mean of 4.6 years. The composite cardiovascular end point was the first occurrence of fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, and cardiovascular mortality. Antihypertensive therapy resulted in an increase in the prevalence of normal transmitral flow pattern from 28% to 46% of patients. Although antihypertensive treatment often resulted in a marked increase in the prevalence of normal mitral valve flow pattern, this was not associated with reduced cardiovascular morbidity and mortality when adjusting for blood pressure, left atrial diameter, LV mass index, and treatment in time-varying Cox analyses. In contrast, lower in-treatment E/A ratios and shorter mitral valve deceleration times were associated with less risk for heart failure. Similarly, normal in-treatment transmitral flow pattern was strongly associated with less risk for heart failure (hazard ratio 0.22, 95% confidence interval 0.05 to 0.98, p = 0.048), even when taking in-treatment left atrial diameter and blood pressure into account. In conclusion, antihypertensive treatment in patients with hypertension with electrocardiographic LV hypertrophy resulted in significant improvement in transmitral flow patterns; this was not associated with reduced cardiovascular morbidity and mortality. However, normal in-treatment LV filling was strongly associated with a reduced risk for hospitalization for heart failure.


Association of smoking with abnormal exercise heart rate responses and long-term prognosis in a healthy, population-based cohort.
Cigarette smoking is associated with chronotropic incompetence, defined as an attenuated heart rate response to exercise. The long-term prognostic implications of this association have not been well explored. Adults enrolled in the Lipid Research Clinics' Prevalence Study who had no history of cardiovascular disease and who were not taking beta-blockers were observed for 12 years. Chronotropic incompetence was assessed as the failure to achieve 90% of an age-predicted target heart rate during an exercise test or as a low chronotropic index, a measure of exercise heart rate response adjusted for age, resting heart rate, and physical fitness. Of the 5,354 eligible participants (mean [+/- SD] age of 44 +/- 10 years; 61% male), 1,931 (36%) smoked cigarettes. Smokers were more likely to have a low chronotropic index (26% versus 16%, odds ratio = 1.8, 95% confidence interval [CI] 1.6 to 2.1) and fail to achieve an age-predicted target heart rate (32% versus 22%, odds ratio = 1.7, 95% CI 1.5 to 2.0). Adjustment for standard cardiac risk factors and physical fitness did not affect these associations. During follow-up, there were 327 deaths. Among subjects without chronotropic incompetence, the relative risk of mortality associated with smoking was moderately increased (hazard ratio = 1.8, 95% CI 1.3 to 2.3); among smokers with chronotropic incompetence, the relative risk of mortality was markedly increased (hazard ratio = 2.7, 95% CI 2.0 to 3.7, P for interaction = 0.02). In this large, middle-aged population-based cohort, smoking was associated with chronotropic incompetence, which in turn identified smokers with a particularly high mortality rate.


Effects of oral domperidone on gastric emptying and motility. A double-blind comparison with placebo and metoclopramide.
The effects of an oral treatment with domperidone on the gastric motor function were investigated in a double-blind study, including 129 patients, referred to the department of radiology for barium meal examination. None of them had an organic obstruction or had had previous gastrointestinal surgery. The patients received either domperidone (50, 20 or 10 mg), metoclopramide (20 mg) or a placebo. The medication was given 30 min before the intake of the barium meal in order to stimulate therapeutic conditions. During the barium meal examination, an assessment was made of the peristaltic activity of the antrum, the gastric emptying and the small bowel transit time. As to these parameters, 50 mg and 20 mg domperidone and 20 mg metoclopramide were significantly superior to the placebo.


Microbial risk assessment of drinking water based on hydrodynamic modelling of pathogen concentrations in source water.
Norovirus contamination of drinking water sources is an important cause of waterborne disease outbreaks. Knowledge on pathogen concentrations in source water is needed to assess the ability of a drinking water treatment plant (DWTP) to provide safe drinking water. However, pathogen enumeration in source water samples is often not sufficient to describe the source water quality. In this study, the norovirus concentrations were characterised at the contamination source, i.e. in sewage discharges. Then, the transport of norovirus within the water source (the river Göta älv in Sweden) under different loading conditions was simulated using a hydrodynamic model. Based on the estimated concentrations in source water, the required reduction of norovirus at the DWTP was calculated using quantitative microbial risk assessment (QMRA). The required reduction was compared with the estimated treatment performance at the DWTP. The average estimated concentration in source water varied between 4.8×10(2) and 7.5×10(3) genome equivalents L(-1); and the average required reduction by treatment was between 7.6 and 8.8 Log10. The treatment performance at the DWTP was estimated to be adequate to deal with all tested loading conditions, but was heavily dependent on chlorine disinfection, with the risk of poor reduction by conventional treatment and slow sand filtration. To our knowledge, this is the first article to employ discharge-based QMRA, combined with hydrodynamic modelling, in the context of drinking water.


Sex difference in the morbidity and pain response with stage 0 of medication-related osteonecrosis of the jaws.
Medication-related osteonecrosis of the jaws (MRONJ) is a potentially severe complication associated with antiresorptive or antiangiogenic therapies. Prior studies, including our own clinical data, have indicated a higher incidence of MRONJ among women compare to men. However, robust evidence establishing a relationship between sex and the prevalence of MRONJ is lacking. We conducted a meta-analysis and utilized murine models to investigate potential sex-based differences in the morbidity associated with MRONJ. Our results revealed no significant difference in the incidence of MRONJ between the sexes when using exposed necrotic bone as a diagnostic criterion. However, a histological examination of the murine models identified the presence of stage 0 MRONJ. Notably, pain assessments across all groups revealed that male mice with stage 0 MRONJ displayed less severe pain symptoms than their female counterparts. Our findings suggested that sex does not contribute to the risk of developing MRONJ. However, considering that approximately 50% of stage 0 MRONJ cases progress to more advanced stages, the less pronounced pain in male patients might delay medical consultation and potentially lead to disease progression. Clinicians should be particularly vigilant about the subdued pain response in male patients with stage 0 MRONJ to prevent disease advancement.


Controlling Plateau-Rayleigh instabilities during the reorganization of silicon macropores in the Silicon Millefeuille process.
The reorganization through high-temperature annealing of closely-packed pore arrays can be exploited to create ultra-thin (<20 µm) monocrystalline silicon layers that can work as cheap and flexible substrates for both the electronic and the photovoltaic industries. By introducing a periodic diameter modulation along deep etched pores, many thin layers can be produced from a single substrate and in a single technological process. Besides the periodicity, the exact shape of the modulation also has a profound impact on the process and subtle profile changes can lead to important differences on the process outcome. In this paper we study both theoretically and experimentally the effect of the initial profile on the pore reorganization dynamics and the morphology of the thin layers obtained through annealing. We show that process reliability, annealing time and final layer characteristics, all can be engineered and optimized by precisely controlling the initial pore profile.


Blockade of the renin-angiotensin system improves cerebral microcirculatory perfusion in diabetic hypertensive rats.
We examined the functional and structural microcirculatory alterations in the brain, skeletal muscle and myocardium of non-diabetic spontaneously hypertensive rats (SHR) and diabetic SHR (D-SHR), as well as the effects of long-term treatment with the angiotensin AT1-receptor antagonist olmesartan and the angiotensin-converting enzyme inhibitor enalapril. Diabetes was experimentally induced by a combination of a high-fat diet with a single low dose of streptozotocin (35 mg/kg, intraperitoneal injection). D-SHR were orally administered with olmesartan (5 mg/kg/day), enalapril (10 mg/kg/day) or vehicle for 28 days, and compared with vehicle-treated non-diabetic SHR or normotensive non-diabetic Wistar-Kyoto rats. The cerebral and skeletal muscle functional capillary density of pentobarbital-anesthetized rats was assessed using intravital fluorescence videomicroscopy. Chronic treatment with olmesartan or enalapril significantly lowered blood pressure and reversed brain functional capillary rarefaction. Brain oxidative stress was reduced to non-diabetic control levels in animals treated with olmesartan or enalapril. Histochemical analysis of the structural capillary density showed that both olmesartan and enalapril increased the capillary-to-fiber ratio in skeletal muscle and the capillary-to-fiber volume density in the left ventricle. Olmesartan and enalapril also prevented collagen deposition and the increase in cardiomyocyte diameter in the left ventricle. Our results suggest that the association between hypertension and diabetes results in microvascular alterations in the brain, skeletal muscle and myocardium that can be prevented by chronic blockade of the renin-angiotensin system.


Farmers' beliefs about bovine tuberculosis control in Northern Ireland.
Beliefs can play an important role in farmer behaviour and willingness to adopt new policies. In Northern Ireland, bovine tuberculosis (bTB) is one of the most important endemic diseases facing the cattle industry. An observational study was conducted on 192 farms in a high bTB incidence area during 2010-2011 in order to obtain a better understanding of farmers' beliefs in relation to bTB control. The views of farmers who had experienced a recent confirmed or multiple reactor bTB breakdowns (cases) were compared to those of farmers who had no recent reactors or restricted herd tests (controls). Data were obtained from a face-to-face questionnaire assessing farmers' agreement to 22 statements. All participating farmers found bTB control important and most were keen to learn more about bTB biosecurity measures and were in favour of the cattle-related bTB control measures as presented in the questionnaire (isolation of skin test inconclusive animals, use of the gamma-interferon test and pre-movement testing). The majority of farmers would allow badger vaccination and culling on their own land with an overall preference for vaccination. Highest disagreement was shown for the statements querying a willingness to pay for bTB control measures. There was agreement on most issues between case and control farmers and between different age groups of farmers although case farmers showed more support for additional advice on bTB biosecurity measures (P = 0.042). Case farmers were also more in favour of allowing badger vaccination (P = 0.008) and culling (P = 0.043) on their land and showed less concern for public opposition (P = 0.048).


Repair of left ventricular-aortic discontinuity complicating endocarditis from an aortic valve prosthesis.
A case of bacterial endocarditis from an aortic valve prosthesis is described in which subannular pseudoaneurysm caused discontinuity of the aorta and left ventricle. Successful repair was accomplished using compound sponge-felt to bolster the left ventricular outflow tract and to obliterate the aneurysm.


Poleward migration of western North Pacific tropical cyclones related to changes in cyclone seasonality.
The average location of observed western North Pacific (WNP) tropical cyclones (TCs) has shifted north over the last several decades, but the cause remains not fully understood. Here we show that, for the annual average, the observed northward migration of WNP TCs is related to changes in TC seasonality, not to a northward migration in all seasons. Normally, peak-season (July-September) TCs form and travel further north than late-season (October-December) TCs. In recent decades, related to less frequent late-season TCs, seasonally higher-latitude TCs contribute relatively more to the annual-average location and seasonally lower-latitude TCs contribute less. We show that the change in TC seasonality is related to the different responses of late-season and peak-season TC occurrence to a stronger Pacific Walker Circulation. Our findings provide a perspective on long-term trends in TC activity, by decomposing the annual-average statistics into seasonal components, which could respond differently to anthropogenic forcing.


Clinical and Vessel Characteristics Associated With Hard Outcomes After PCI and Their Combined Prognostic Implications.
Background Cardiac death or myocardial infarction still occurs in patients undergoing contemporary percutaneous coronary intervention (PCI). We aimed to identify adverse clinical and vessel characteristics related to hard outcomes after PCI and to investigate their individual and combined prognostic implications. Methods and Results From an individual patient data meta-analysis of 17 cohorts of patients who underwent post-PCI fractional flow reserve measurement after drug-eluting stent implantation, 2081 patients with available clinical and vessel characteristics were analyzed. The primary outcome was cardiac death or target-vessel myocardial infarction at 2 years. The mean age of patients was 64.2±10.2 years, and the mean angiographic percent diameter stenosis was 63.9%±14.3%. Among 11 clinical and 8 vessel features, 4 adverse clinical characteristics (age ≥65 years, diabetes, chronic kidney disease, and left ventricular ejection fraction <50%) and 2 adverse vessel characteristics (post-PCI fractional flow reserve ≤0.80 and total stent length ≥54 mm) were identified to independently predict the primary outcome (all P<0.05). The number of adverse vessel characteristics had additive predictability for the primary end point to that of adverse clinical characteristics (area under the curve 0.72 versus 0.78; P=0.03) and vice versa (area under the curve 0.68 versus 0.78; P=0.03). The cumulative event rate increased in the order of none, either, and both of adverse clinical characteristics ≥2 and adverse vessel characteristics ≥1 (0.3%, 2.4%, and 5.3%; P for trend <0.01). Conclusions In patients undergoing drug-eluting stent implantation, adverse clinical and vessel characteristics were associated with the risk of cardiac death or target-vessel myocardial infarction. Because these characteristics showed independent and additive prognostic value, their integrative assessment can optimize post-PCI risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04684043. www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42021234748.


Noninvasive transcutaneous ultrasound augments thrombolysis in the left circumflex coronary artery--an in vivo canine study.
Ultrasound has the potential to augment chemical thrombolysis. Thrombotic occlusions in the left circumflex artery (LCx) were induced in 27 dogs. Sixty minutes later, tissue-type plasminogen activator (t-PA) was given intravenously over 90 min. Thrombotic occlusions (n = 20) were treated with concomitant transcutaneous low frequency (27 kHz), continuous wave (CW) (n = 10) or pulsed wave (PW) (n = 10) ultrasound. Tissue-type plasminogen activator plus ultrasound (n = 20) vs. tissue-type plasminogen activator alone (n=7) resulted in more frequent Thrombolysis in Myocardial Infarction (TIMI) 3 flow (90% vs. 43%, P = 0.024) and less reocclusion (11% vs. 67%, P = 0.080). At 60 min, median TIMI grade flow for tissue-type plasminogen activator alone was 2 (mean: 1.43 +/- 1.40) compared to 3 (mean: 2.70 +/- 0.95) for tissue-type plasminogen activator plus continuous as well as pulsed wave ultrasound (P = 0.035). Continuous wave and pulsed wave ultrasound were equally effective in augmenting thrombolysis. Histologically, no ultrasound-mediated injury to the myocardium or coronary arteries occurred. Both transcutaneous low frequency continuous wave ultrasound and pulsed wave ultrasound enhance tissue-type plasminogen activator-mediated thrombolysis of the posterior circulation with higher TIMI 3 flow rates and less reocclusion than with tissue-type plasminogen activator alone. In addition, at the energy levels used, low frequency ultrasound appears safe.


Preparation of novel aminated chitosan schiff's base derivative for the removal of methyl orange dye from aqueous environment and its biological applications.
A novel, eco-friendly aminated chitosan Schiff's base (ACSSB@ZnO) was developed and utilized to remove MO from aqueous environment. The impact of different significant parameters, for example, pH (3-11), adsorbent dose (0.1-0.6 g), contact time (0-120 min), and temperature (303-323 K) have been explored by batch process. Kinetic data was illustrated by pseudo-second-order model and the isotherms fitted well with Langmuir isotherm model. The highest sorption capacity of ACSSB@ZnO was observed to be 111.11 mg/g at 323 K. Positive enthalpy and entropy values demonstrated that the MO adsorption procedure was an endothermic. Negative Gibbs free energy values implied the spontaneous nature of the adsorption system. Moreover, reusability experiments were studied and it can be regenerated by using NaOH as effluent.


Host functional and phylogenetic composition rather than host diversity structure plant-herbivore networks.
Declining plant diversity alters ecological networks, such as plant-herbivore interactions. However, our knowledge of the potential mechanisms underlying effects of plant species loss on plant-herbivore network structure is still limited. We used DNA barcoding to identify herbivore-host plant associations along declining levels of tree diversity in a large-scale, subtropical biodiversity experiment. We tested for effects of tree species richness, host functional and phylogenetic diversity, and host functional (leaf trait) and phylogenetic composition on species, phylogenetic and network composition of herbivore communities. We found that phylogenetic host composition and related palatability/defence traits but not tree species richness significantly affected herbivore communities and interaction network complexity at both the species and community levels. Our study indicates that evolutionary dependencies and functional traits of host plants determine the composition of higher trophic levels and corresponding interaction networks in species-rich ecosystems. Our findings highlight that characteristics of the species lost have effects on ecosystem structure and functioning across trophic levels that cannot be predicted from mere reductions in species richness.


Mandibular involvement in patients with multiple myeloma.
A survey of changes in the jaw bones of 38 patients with multiple myeloma revealed five cases with mandibular involvement. One case showed a pathological fracture of the mandibular angle, and in another case, a radiolucent area was found in the body of the mandible. These two clinical findings led to the diagnosis of multiple myeloma. The other three cases had no symptoms related to the oral region. All five cases also showed typical "punched-out" lesions in the skull. It is suggested that a skeletal radiologic survey including the jaw should be performed in patients with multiple myeloma.


Robotic colorectal cancer surgery in China: a nationwide retrospective observational study.
Robotic colorectal cancer surgery is widely accepted and applied. However, there is still no objective and comprehensive assessment on the data of nationwide multicenter series. A total of 28 medical centers in Mainland China participated in this nationwide retrospective observational study. From the first case performed in each center to the last until December 2017, patients with robotic resection for primary tumor and pathologically confirmed colorectal adenocarcinoma were consecutively enrolled. Clinical, pathological and follow-up data were collected and analyzed. A total of 5389 eligible patients were finally enrolled in this study, composing 72.2% of the total robotic colorectal surgery volume of Mainland China in the same period. For resections of one bowel segment of primary tumor, the postoperative mortality rate was 0.08% (4/5063 cases), and the postoperative complication rate (Clavien-Dindo grade II or higher) was 8.6% (434/5063 cases). For multiple resections, the postoperative mortality rate was 0.6% (2/326 cases), and the postoperative complication rate was 16.3% (53/326 cases). Out of 2956 patients receiving sphincter-preserving surgery in only primary resection, 130 (4.4%) patients had anastomotic leakage. Traditional low anterior resection (tumor at middle rectum) (OR 2.384, P < 0.001), traditional low anterior resection (tumor at low rectum) (OR 1.968, P = 0.017) and intersphincteric resection (OR 5.468, P = 0.006) were significant independent risk factors for anastomotic leakage. Female gender (OR 0.557, P = 0.005), age ≥ 60 years (OR 0.684, P = 0.040), and preventive stoma (OR 0.496, P = 0.043) were significant independent protective factors. Body mass index, preoperative chemotherapy/radiotherapy, tumor size, and TNM stage did not independently affect the occurrence of anastomotic leakage. Robotic colorectal cancer surgery was safe and reliable and might have advantages in patients at high risk of anastomotic leakage.


Dysregulated Genes and Signaling Pathways in the Formation and Rupture of Intracranial Aneurysm.
Intracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subsequently, candidate genes were validated at both transcript and protein level. There were 314 DGs in patients with unruptured IA when compared to control samples. Out of these, SPARC and OSM were validated as candidate molecules in unruptured IA. PI3K-AKT signaling pathway was found to be an important pathway for the formation of IA. Similarly, 301 DGs were identified in the samples of ruptured IA when compared with unruptured IAs. CTSL was found to be a key candidate molecule which along with Hippo signaling pathway may be involved in the rupture of IA. We conclude that activation of PI3K-AKT signaling pathway by OSM along with up-regulation of SPARC is important for the formation of IA. Further, regulation of Hippo pathway through PI3K-AKT signaling results in the down-regulation of YAP1 gene. This along with up-regulation of CTSL leads to further weakening of aneurysm wall and its subsequent rupture.


Bupivacaine Field Block With Clonidine for Postoperative Pain Control in Posterior Spine Approaches: A Randomized Double-Blind Trial.
The synergistic effect of clonidine with bupivacaine, well established in peripheral nerve blocks, remains controversial in local field block for postoperative analgesia. To investigate the potential analgesic benefit of adding clonidine to bupivacaine during preincisional field block in posterior approaches for spine surgeries. Two hundred twenty-five patients were enrolled in this study and underwent lumbar spinal fusion (n = 80), lumbar laminectomy (n = 25), lumbar microdiscectomy (n = 94), or cervical laminectomy (n = 26). In each surgical subgroup, patients were randomly assigned in a double-blinded fashion to receive either 20 mL of 0.25% bupivacaine alone (control group, n = 109) or with 150 μg clonidine (clonidine group, n = 116) in the form of a preincisional field block. Outcome parameters included area under the curve of pain from postoperative day D0 to D8 and rescue morphine consumption from D0 to D3. The area under the curve was reduced in the clonidine group, particularly in the microdiscectomy subgroup, and without reaching statistical significance in the cervical laminectomy subgroup. Total rescue morphine consumption was reduced in the clonidine group, particularly at D1-D2, a benefit that was exclusive to the lumbar stenosis and lumbar fusion subgroups. Field block with clonidine, surgical subgroup, and the presence of preoperative spinal pain were factors independently influencing postoperative wound pain in multivariate analysis. The addition of clonidine to local preincisional field block with bupivacaine resulted in better and prolonged postoperative analgesia in posterior lumbar spine surgeries, an effect that was more pronounced in patients with no preoperative spinal pain.


Inhibition of human telomerase by diphosphates of acyclic nucleoside phosphonates.
Diphosphates of the antiviral acyclic nucleoside phosphonates (ANPs) were evaluated in telomeric repeat amplification protocol (TRAP) for their ability to inhibit the extension of telomeres by human telomerase. Extracts from human leukaemia HL-60 cells were used as a source of the enzyme. Data show that the most effective compound studied was the guanine derivative PMEGpp (IC50 12.7+/-0.5 micromolL(-1) at 125 micromolL(-1) deoxynucleoside triphosphates (dNTPs)). The inhibitory effects of other PME, PMP and HPMP diphosphates on telomerase reverse transcriptase decreased in the order: (R)-PMPGpp>(R)-HPMPGpp>PMEDAPpp>(S)-PMPGpp>(S)-HPMPApp>PMEO-DAPypp>(R)-6-cyprPMPDAPpp>(R)-PMPApp>(R)-PMPDAPpp> or =PMEApp> or =PMECpp>PMETpp>(S)-PMPApp approximately 6-Me2PMEDAPpp. These results are consistent with the observed antineoplastic activities of the parental guanine (PMEG) and 2,6-diaminopurine (PMEDAP) PME-derivatives. Moreover, structure-activity relationship indicates enantioselectivity of some of these human telomerase inhibitors: (R)-isomers of the PMP-derivatives possess stronger inhibitory potency towards the enzyme than (S)-isomers. The data may contribute to the rational design of telomerase inhibitors based on the structure of acyclic nucleotide analogues.