Pathophysiology of brain ischemia as it relates to the therapy of acute ischemic stroke.
Current knowledge of the pathophysiology of cerebral ischemia, summarized in the present study, predicts that neurological deficits caused by moderate ischemia (flows in the penumbral range between 23 and 10 ml/100 g/min) are reversible provided flow is restored within 3-4 h of onset. It also predicts that areas of dense ischemia cannot be salvaged and that reperfusion of such areas is risky, because massive edema or even hemorrhage may develop following reperfusion. On this basis, it is argued that selection of stroke cases for thrombolysis or surgical revascularization must be based not only on computed tomographic (CT) scanning to exclude hemorrhagic stroke, but also on cerebral blood flow (CBF) tomography to exclude lacunar infarcts, early reperfusion, and dense ischemia. The methods available for routing CBF tomography in acute stroke cases are discussed, and it is concluded that single photon emission computed tomography (SPECT) using [99mTc]hexamethyl propyleneamine oxide (HM-PAO) or [99mTc]ethyl cysteinate dimer (ECD) should be explored for this use. In concluding, the glutamate receptor antagonist is mentioned. This compound is therapeutically active in some animal stroke models. In humans, it is probably used only in the acute phase, and in those in whom some degree of collateral flow is preserved. Therefore, even with this therapeutic approach, CBF tomography may be of value for patient selection.


A field study to estimate the prevalence of Trypanosoma equiperdum in Mongolian horses.
From May to July 2000, a cross-sectional study was conducted to estimate the prevalence of Trypanosoma equiperdum in the horse population of the central province (Tuv aimag) of Mongolia. On average, four herds were selected from each of the 29 aimag subdivisions (119 herds). From each herd, 10 horses were sampled in proportion to sex and age categories in the respective herds (1190 horses). Sera from 1122 horses were analysed for T. equiperdum antibodies using two serological assays, the complement fixation test (CFT) and the enzyme-linked immunosorbent assay (ELISA). The crude estimate of the CFT and the ELISA seroprevalence was 7.6 and 6.7%, respectively. Concordance between the CFT and ELISA results was high (96%). The highest number of CFT positive animals was detected in one herd in Möngönmorit (6/10), followed by herds in Bayandelger (5/10) and in Bayantsagaan (5/10). Poor body condition was significantly correlated with positive serological status in both CFT and ELISA. A history of abortion appeared to be a risk factor for both CFT and ELISA seropositivity. Blood samples of all horses belonging to herds with at least three (3/10) seropositive animals (CFT and/or ELISA) were analysed by light microscopy and by PCR using a Trypanosoma (Trypanozoon) brucei specific primer pair. No trypanosomes or any other haemoparasites could be detected in Giemsa stained thin blood smears. Eight out of the 130 samples (6.2%) analysed by PCR gave positive signals. Seven out of the eight PCR positive horses were also serologically positive. One PCR (and ELISA) positive stallion from Möngönmorit showed emaciation, scrotal and preputial oedema and an oedematous skin plaque. From the serological and DNA-based results it is concluded, that trypanosome infections occur in horses in the Tuv aimag of Mongolia. Since at present neither serological nor DNA-based tests allow a subspecies specific identification within the subgenus Trypanozoon, no definitive diagnosis can be given for T. equiperdum. Whether the examined herds are infected with T. equiperdum or with T. evansi, the causative agent of surra, remains an open question. However, based on the clinical findings, the negative parasitological results and the concentration of conspicuous seroprevalences in single herds, circumstantial evidence supports the existence of infections with the causative agent of dourine.


Tumour markers as prognostic aids in prostatic carcinoma.
Of 102 patients suffering from prostatic carcinoma, complete data on the serum concentration of 7 tumour markers were available from 90 patients, together with tumour grade, local stage and the presence or absence of skeletal metastases. The serum content of prostatic acid phosphatase, prostate specific antigen, neopterin, thymidine kinase, osteocalcin, C-reactive protein and tissue polypeptide antigen was measured. By means of Cox's regression and multivariate analysis the ability of these variables to predict prognosis, i.e. death from prostatic cancer, was studied. Neopterin appeared to be the most efficient marker, followed by tumour grade, thymidine kinase and prostate specific antigen. No other variable provided information of statistical significance. In multivariate analysis thymidine kinase performed best, followed by neopterin, tumour grade and prostate specific antigen. Several serum tumour markers reflect the biological activity of human prostate cancers and their value should be further explored. They may become useful in the management of individual patients.


Intravenous esmolol infusion improves surgical fields during sevoflurane-anesthetized endoscopic sinus surgery: a double-blind, randomized, placebo-controlled trial.
There is increasing evidence to support the use of anesthetics to affect operative fields during endoscopic sinus surgery and thus the speed, thoroughness, and safety of the surgery itself. Previous research has suggested preoperative beta-blockers improve surgical fields (SFs); our study is novel in showing the impact of a beta-blocker infusion on SFs during sinus surgery. A prospective, randomized, double-blind, placebo-controlled trial was conducted in 40 patients. Patients undergoing endoscopic sinus surgery for chronic rhinosinusitis received a constant infusion of i.v. esmolol or saline in addition to a standard inhaled anesthetic protocol. At regular 15-minutes intervals, the quality of SF, heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were assessed. Total blood loss was also recorded. Average vital sign parameters (HR/SBP/DBP) were significantly lower in the esmolol group (69.1/90.2/55.1 versus 77.2/99.5/63.5; p < 0.01). The esmolol infusion improved SFs relative to control (2.3 versus 2.6; p = 0.045). Esmolol infusion resulted in good SFs (grades 1 and 2) more often than poor fields (grades 3 and 4); on the contrary, the control group showed more poor than good SFs (chi-square; p = 0.04). A correlation between increasing HR and worsening SFs was identified (r = 0.259; p = 0.002). The control group had significantly higher average blood loss (1.3 versus 0.8 mL/min; p = 0.037). Esmolol-induced relative hypotension and bradycardia during endoscopic sinus surgery achieves significantly improved SFs relative to saline control.


Fresh Whole Blood transfusions in the austere environment.
The use of Fresh Whole Blood (FWB) transfusions can be a powerful tool for the Special Operations Forces (SOF) medic to treat uncontrolled hemorrhage. In fact, it may be the only tool currently available for hemostatic resuscitation, which along with hypotensive resuscitation, forms the basis for Damage Control Resuscitation (DCR). Until now, no comprehensive protocol has existed for conducting FWB transfusions in austere environments. The United States Special Operations Command (USSOCOM) sponsored Curriculum Evaluation Board (CEB), which is responsible for authoring the Tactical Emergency Medical Protocols (TMEPs) has produced a protocol. This article serves as its introduction.


Study of Lability and Kinetics of the Main Carotenoid Pigments of Red Pepper in the De-esterification Reaction.
Different concentrations of potassium hydroxide in methanol were used to control the time required for complete de-esterification of the carotenoids present in paprika oleoresin, and the effectiveness of the overall process was determined. With concentrated solutions of potash, 20% and 30% (w/v), the reaction was completed in a shorter time but the overall process was less effective. Solutions of low concentration, 5% and 10% (w/v), enabled the kinetic study to be carried out and the rates of de-esterification for individual pigments to be compared. The effect that the fatty acid esterifying each carotenoid had on the reaction was deduced. The pigments esterified by long-chain fatty acids had a higher rate of de-esterification than those bonded with short-chain fatty acids.


The Rydberg constant and proton size from atomic hydrogen.
At the core of the "proton radius puzzle" is a four-standard deviation discrepancy between the proton root-mean-square charge radii (rp) determined from the regular hydrogen (H) and the muonic hydrogen (µp) atoms. Using a cryogenic beam of H atoms, we measured the 2S-4P transition frequency in H, yielding the values of the Rydberg constant R∞ = 10973731.568076(96) per meterand rp = 0.8335(95) femtometer. Our rp value is 3.3 combined standard deviations smaller than the previous H world data, but in good agreement with the µp value. We motivate an asymmetric fit function, which eliminates line shifts from quantum interference of neighboring atomic resonances.


Multivariate analysis.
One of the goals of Current Protocols is to provide information from the very basic level to the very advanced. This unit is an excellent example of providing explanation and application for a complex area. Building upon several other units on data analysis, it provides a detailed explanation of how multivariate analytical techniques are applied to flow cytometry data. The unit deals with the covariance matrix, principal component analysis, and cluster analysis and provides sources for software as well as example data files. This material will be particularly valuable to the graduate student trying to obtain a good understanding of statistical methods in flow cytometry, as well as to the experienced investigator who uses these tools on a regular basis without really understanding how they operate. principal components analysis; cluster analysis; FCS file format One of the goals of Current Protocols is to provide information from the very basic level to the very advanced.


Mitochondrial genome instability and mtDNA depletion in human cancers.
An increase in the rate of glycolysis is one of the metabolic alterations in most cancer cells. However, the role of alterations in mitochondrial function and mitochondrial DNA (mtDNA) in carcinogenesis still remains unclear. In this study, we analyzed the nucleotide sequence of the D-loop and the copy number of mtDNA in 54 hepatocellular carcinomas (HCCs), 31 gastric, 31 lung, and 25 colorectal cancers as well as their corresponding non-tumorous tissues. The results revealed that 42.6% (23/54) of the HCCs, 51.6% (16/31) of the gastric cancers, 22.6% (7/31) of the lung cancers, and 40.0% (10/25) of the colorectal cancers harbored mutation(s) in the D-loop of mtDNA. The mtDNA mutations in 43.5% (10/23) of the HCCs, 62.5% (10/16) of the gastric cancers, 57.1% (4/7) of the lung cancers, and 90.0% (9/10) of the colorectal cancers were changes in the mononucleotide or dinucleotide repeats, deletions, or multiple insertions. Moreover, we found that there is a significant decrease in mtDNA copy number in 57.4% (31/54) of the HCCs, 54.8% (17/31) of the gastric cancers, 22.6% (7/31) of the lung cancers, and 28.0% (7/25) of the colorectal cancers compared with the corresponding non-tumorous tissues. It is noteworthy that the incidence of somatic mutations in the D-loop of mtDNA in the cancers of later stages was higher than that of the early-stage cancers. Taken together, our findings suggest that instability in the D-loop region of mtDNA, together with the decrease in mtDNA copy number, is involved in the carcinogenesis of human cancers.


Machine Learning in Nuclear Medicine: Part 2-Neural Networks and Clinical Aspects.
This article is the second part in our machine learning series. Part 1 provided a general overview of machine learning in nuclear medicine. Part 2 focuses on neural networks. We start with an example illustrating how neural networks work and a discussion of potential applications. Recognizing that there is a spectrum of applications, we focus on recent publications in the areas of image reconstruction, low-dose PET, disease detection, and models used for diagnosis and outcome prediction. Finally, since the way machine learning algorithms are reported in the literature is extremely variable, we conclude with a call to arms regarding the need for standardized reporting of design and outcome metrics and we propose a basic checklist our community might follow going forward.


A Deep-Learning Algorithm (ECG12Net) for Detecting Hypokalemia and Hyperkalemia by Electrocardiography: Algorithm Development.
The detection of dyskalemias-hypokalemia and hyperkalemia-currently depends on laboratory tests. Since cardiac tissue is very sensitive to dyskalemia, electrocardiography (ECG) may be able to uncover clinically important dyskalemias before laboratory results. Our study aimed to develop a deep-learning model, ECG12Net, to detect dyskalemias based on ECG presentations and to evaluate the logic and performance of this model. Spanning from May 2011 to December 2016, 66,321 ECG records with corresponding serum potassium (K+) concentrations were obtained from 40,180 patients admitted to the emergency department. ECG12Net is an 82-layer convolutional neural network that estimates serum K+ concentration. Six clinicians-three emergency physicians and three cardiologists-participated in human-machine competition. Sensitivity, specificity, and balance accuracy were used to evaluate the performance of ECG12Net with that of these physicians. In a human-machine competition including 300 ECGs of different serum K+ concentrations, the area under the curve for detecting hypokalemia and hyperkalemia with ECG12Net was 0.926 and 0.958, respectively, which was significantly better than that of our best clinicians. Moreover, in detecting hypokalemia and hyperkalemia, the sensitivities were 96.7% and 83.3%, respectively, and the specificities were 93.3% and 97.8%, respectively. In a test set including 13,222 ECGs, ECG12Net had a similar performance in terms of sensitivity for severe hypokalemia (95.6%) and severe hyperkalemia (84.5%), with a mean absolute error of 0.531. The specificities for detecting hypokalemia and hyperkalemia were 81.6% and 96.0%, respectively. A deep-learning model based on a 12-lead ECG may help physicians promptly recognize severe dyskalemias and thereby potentially reduce cardiac events.


A development of symmetric extension method for subband image coding.
Describes the development of a technique for subband image coding called the symmetric extension method which utilizes the nature of a symmetrically extended image to achieve high quality coding. There are, however, some restrictions on the usable subband coding system. The development is done based on the property of a symmetrically extended signal in the analysis process to remove the restriction. The behavior of the sequence after two processes, filtering and decimation, is examined and formulated. The development extends the application area of the technique.


Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy.
Peripheral fat loss and visceral fat gain have been reported in HIV infection. There are limited data on long-term change in adipose tissue in HIV-infected patients vs. controls. Therefore, we determined change in regional adipose tissue from baseline examination to 5 years later among participants in the study of Fat Redistribution and Metabolic Change in HIV Infection. Regional adipose tissue volume was measured using MRI at both examinations in 477 HIV-infected and 214 control men and women. Lipoatrophy was defined as leg subcutaneous adipose tissue (SAT) below the cutoff point marking the lowest decile (10%) of controls at each examination. HIV-infected and control participants showed similar adipose tissue gains. In men, all SAT depots and visceral adipose tissue started lower and remained lower on average in HIV-infected vs. controls. In women, leg and arm SAT also started lower and remained lower in HIV-infected vs. controls. Mean leg SAT of HIV-infected men was 67% of control men at baseline and 65% at follow-up; for women 83% and 77%. At baseline, 48% of HIV-infected participants had lipoatrophy; on average those with baseline lipoatrophy gained 0.96L of leg SAT compared with 1.23L gain for controls in the lowest decile (P = 0.16). At follow-up, 53% of HIV-infected participants had lipoatrophy. In multivariable models, discontinuation of stavudine appeared to produce little gain in leg SAT ( approximately 1.1%/year). HIV-infected participants did not substantially recover SAT compared with controls, although both showed average gains. HIV-associated lipoatrophy persisted after 5 years of follow-up.


Happiness in Plastic Surgery: A Cross-Sectional Analysis of 595 Practicing Plastic Surgeons, Fellows, Residents, and Medical Students.
Despite a heightened appreciation for wellness in medicine, there exists little information specific to plastic surgery. The purpose of this research was to assess happiness within the field of plastic surgery. A cross-sectional study was conducted in July of 2017 by distributing an American Society of Plastic Surgeons sponsored survey to a random cohort of current practicing American Society of Plastic Surgeons members, residents and fellows. In addition, the same survey was sent to medical students applying to integrated plastic surgery residency. Total happiness scores (Subjective Happiness Scale) were averaged and compared between and within surveyed groups. A total of 595 individuals completed surveys, including 287 practicing surgeons, 116 residents, 12 fellows, and 180 medical students. Differences in happiness scores between the groups were statistically significant (P < 0.01). For practicing physicians, happiness scores were significantly greater for those more than 20 years out from training (P < 0.01). Furthermore, a significantly positive correlation was found between practice expectations coming out of residency and happiness scores (Pearson correlation coefficient, 0.2; P < 0.01). Despite the prevalence of burnout and mental health disorders associated with a career in medicine, plastic surgeons and trainees report high levels of happiness. Practicing plastic surgeons report increased happiness further out from training and when meeting practice expectations coming out of training. Otherwise, there were no significant differences in happiness between groups. Regarding sex, it is encouraging to report no significant sex discrepancies with happiness in a field where women still face significant adversity.


The frequency of unsuspected minor illness or injury in intoxicated patients.
To determine the frequency of unsuspected minor illness or injury in a group of patients frequently seen in the ED for acute intoxication. The medical records of the 20 patients seen most frequently in the ED for acute intoxication in 1993 were reviewed for the number of ED visits for intoxication, the number of associated documented episodes of minor trauma or illness, the extent of ED workup of discovered illness or injury, and patient disposition from the ED. The 20 study patients were evaluated in the ED 1,858 times in 1993 for acute intoxication, a mean of 92.5 visits/patient (+/- 26.6). The most frequent injury was minor trauma above the neck, occurring a mean of 9 times (+/- 3.6) in each of the study patients during 1993. Evaluation included repeated neurologic examinations and frequent radiography of the cervical spine (n = 80), skull (n = 5), facial bones (n = 6), and mandible (n = 5). A limited number of head CT scans also were done (n = 8). The most frequent minor illnesses were gastritis (n = 7), managed with hydration, and mild hypothermia (n = 6), managed with passive rewarming. The incidence of unsuspected minor illness or injury in this patient group was substantial. While most unsuspected medical problems had little clinical significance, some were potentially dangerous, and some necessitated hospitalization (e.g., hypothermia, hematemesis, and respiratory depression).


Symmetrical peripheral gangrene due to Plasmodium falciparum malaria.
A 45-year-old man presented with a 4-day history of high-grade fever with rigours and a 2-day history of painful bluish black discolouration of extremities (acrocyanosis). He was haemodynamically stable and all peripheral pulses palpable, but the extremities were cold with gangrene involving bilateral fingers and toes. Mild splenomegaly was present on abdominal examination but rest of the physical examinations were normal. On investigating he was found to have anaemia, thrombocytopaenia with gametocytes of Plasmodium falciparum on peripheral blood smear. His blood was uncoagulable during performance of prothrombin time with a raised D-dimer. Oxygen saturation was normal and the arterial Doppler test showed reduced blood flow to the extremities. A diagnosis of complicated P. falciparum malaria with disseminated intravascular coagulation (DIC) leading to symmetrical peripheral gangrene was performed. Artemisinin combination therapy was started and heparin was given for DIC. A final line of demarcation of gangrene started forming by 12th day.


Analysis of Digital Documentation Speed and Sequence Using Digital Paper and Pen Technology During the Refugee Crisis in Europe: Content Analysis.
The Syria crisis has forced more than 4 million people to leave their homeland. As a result, in 2016, an overwhelming number of refugees reached Germany. In response to this, it was of utmost importance to set up refugee camps and to provide humanitarian aid, but a health surveillance system was also implemented in order to obtain rapid information about emerging diseases. The present study describes the effects of using digital paper and pen (DPP) technology on the speed, sequence, and behavior of epidemiological documentation in a refugee camp. DPP technology was used to examine documentation speed, sequence, and behavior. The data log of the digital pens used to fill in the documentation was analyzed, and each pen stroke in a field was recorded using a timestamp. Documentation time was the difference between first and last stroke on the paper, which includes clinical examination and translation. For three months, 495 data sets were recorded. After corrections had been made, 421 data sets were considered valid and subjected to further analysis. The median documentation time was 41:41 min (interquartile range 29:54 min; mean 45:02 min; SD 22:28 min). The documentation of vital signs ended up having the strongest effect on the overall time of documentation. Furthermore, filling in the free-text field clinical findings or therapy or measures required the most time (mean 16:49 min; SD 20:32 min). Analysis of the documentation sequence revealed that the final step of coding the diagnosis was a time-consuming step that took place once the form had been completed. We concluded that medical documentation using DPP technology leads to both an increase in documentation speed and data quality through the compliance of the data recorders who regard the tool to be convenient in everyday routine. Further analysis of more data sets will allow optimization of the documentation form used. Thus, DPP technology is an effective tool for the medical documentation process in refugee camps.


Chromatographic investigation of the glycosylation pattern of alpha-1-acid glycoprotein secreted by the HepG2 cell line; a putative model for inflammation?
In certain pathophysiological conditions, such as rheumatoid arthritis, there are alterations in the glycosylation pattern of the acute phase protein, alpha-1-acid glycoprotein (AGP). These changes are likely to be functionally significant, however, verification of the latter role requires a system which reflects in vivo glycosylation changes in AGP and also produces sufficient quantities of the protein for further study. The human hepatoma cell line HepG2 is documented as displaying a shift in the glycosylation pattern of glycoproteins from normal state to acute phase after stimulation with inflammatory mediators. We have isolated AGP from the culture medium of HepG2 cells both before and after stimulation with a cytokine preparation and analysed the glycosylation pattern of each preparation, after enzymatic release, by high pH anion-exchange chromatography. Before stimulation, the glycosylated population was similar to a profile of AGP isolated from normal plasma; however, cytokine stimulation resulted in a shift to a profile which was consistent with that of AGP from a rheumatoid arthritis sufferer. Thus a HepG2 cell culture system is capable of being a crude model of the changes in glycosylation of acute phase proteins although it has a tendency to produce oligosaccharide chains which are not fully sialylated.


A Case Report on Lateral Proboscis: A Rare Congenital Anomaly.
Lateral proboscis is a rare congenital condition characterized by a cylindrical protuberance on the nasofrontal region accompanied by abnormal nasal development on the affected side. We aimed to describe the management of the lateral proboscis in staged repair. A 7-year-old girl came with a tube-like projection on the left medial canthal region and nasal agenesis on the ipsilateral side. She was diagnosed with lateral proboscis, left microphthalmia, lower eye lid coloboma, and asymmetry in the orbital region. The patient has undergone 3 major surgeries at our institution. The first surgery involved the deconstruction of the tube to form the left nasal body and nostril. The second operation involved trimming of the new nose form and the excision of the bony protrusion directly beneath the base of the pedicle through bifrontal craniotomy. The remaining bone defect was closed using a pericranial flap. The orbital floor was reconstructed using titanium mesh. The third operation involved nasal reconstruction using a costal cartilage graft to create a dorsal nasal and alar framework. The patient healed with no complications, had become less reserved and her grades improved significantly after the operation. Further appointments are being scheduled to evaluate growth distortion and the resulting facial asymmetry. Surgical correction will be planned thereafter to further reconstruct the facial features. Evaluation of patient is necessary to explore possible clinical outcomes and corresponding treatment options. Multidisciplinary management is highly recommended, involving plastic surgeons, neurosurgeons, ophthalmologists, pediatricians, and pediatric psychiatrists in order to improve patient's quality of life.


Airline pilot disability: the continued experience of a major US airline.
This study details our continued experience with preemployment screening and medical disability in a large group of pilots from one airline from 1975 through 1982. During this period, 368 pilot applicants underwent preemployment screening and 73 of these were rejected for employment because of medical reasons. The majority (45) of these were unsuitable for psychological reasons. Medical disability accounted for approximately 20% of the pilots separated from the company during the period of study. Age-specific disability rates increased rapidly after age 45 years, with cardiovascular disease responsible for more than 50% of these medical losses. Disability rates of older pilots have decreased considerably compared with previous rates: the age-adjusted rate for pilots age 45 years or older has decreased from 27.50/1,000 person-years to 8.97/1,000 person-years (p less than 0.0001). The reasons for this reduction remain unclear, but changes in the interpretation of the Federal Aviation Administration regulations and changes in company policies may have contributed. The role of preventive medicine in the form of regular medical surveillance is uncertain, with no direct evidence of a beneficial effect.


Evaluation of similarity measures for use in the intensity-based rigid 2D-3D registration for patient positioning in radiotherapy.
Rigid 2D-3D registration is an alternative to 3D-3D registration for cases where largely bony anatomy can be used for patient positioning in external beam radiation therapy. In this article, the authors evaluated seven similarity measures for use in the intensity-based rigid 2D-3D registration using a variation in Skerl's similarity measure evaluation protocol. The seven similarity measures are partitioned intensity uniformity, normalized mutual information (NMI), normalized cross correlation (NCC), entropy of the difference image, pattern intensity (PI), gradient correlation (GC), and gradient difference (GD). In contrast to traditional evaluation methods that rely on visual inspection or registration outcomes, the similarity measure evaluation protocol probes the transform parameter space and computes a number of similarity measure properties, which is objective and optimization method independent. The variation in protocol offers an improved property in the quantification of the capture range. The authors used this protocol to investigate the effects of the downsampling ratio, the region of interest, and the method of the digitally reconstructed radiograph (DRR) calculation [i.e., the incremental ray-tracing method implemented on a central processing unit (CPU) or the 3D texture rendering method implemented on a graphics processing unit (GPU)] on the performance of the similarity measures. The studies were carried out using both the kilovoltage (kV) and the megavoltage (MV) images of an anthropomorphic cranial phantom and the MV images of a head-and-neck cancer patient. Both the phantom and the patient studies showed the 2D-3D registration using the GPU-based DRR calculation yielded better robustness, while providing similar accuracy compared to the CPU-based calculation. The phantom study using kV imaging suggested that NCC has the best accuracy and robustness, but its slow function value change near the global maximum requires a stricter termination condition for an optimization method. The phantom study using MV imaging indicated that PI, GD, and GC have the best accuracy, while NCC and NMI have the best robustness. The clinical study using MV imaging showed that NCC and NMI have the best robustness. The authors evaluated the performance of seven similarity measures for use in 2D-3D image registration using the variation in Skerl's similarity measure evaluation protocol. The generalized methodology can be used to select the best similarity measures, determine the optimal or near optimal choice of parameter, and choose the appropriate registration strategy for the end user in his specific registration applications in medical imaging.


Tribology and its growing use toward the study of food oral processing and sensory perception.
Here we provide a comprehensive review of the knowledge base of soft tribology, the study of friction, lubrication, and wear on deformable surfaces, with consideration for its application toward oral tribology and food lubrication. Studies on "soft-tribology" have emerged to provide knowledge and tools to predict oral behavior and assess the performance of foods and beverages. We have shown that there is a comprehensive set of fundamental literature, mainly based on soft contacts in the Mini-traction machine with rolling ball on disk configuration, which provides a baseline for interpreting tribological data from complex food systems. Tribology-sensory relationships do currently exist. However, they are restricted to the specific formulations and tribological configuration utilized, and cannot usually be applied more broadly. With a careful and rigorous formulation/experimental design, we envisage tribological tools to provide insights into the sensory perception of foods in combination with other in vitro technique such as rheology, particle sizing or characterization of surface interactions. This can only occur with the use of well characterized tribopairs and equipment; a careful characterization of simpler model foods before considering complex food products; the incorporation of saliva in tribological studies; the removal of confounding factors from the sensory study and a global approach that considers all regimes of lubrication.


[The anti-inflammatory activity of intal and beta-carotene in a model of experimental granulomatous lung inflammation].
A-25 sephadex-induced granulomatous inflammation of the lungs in rats was treated with beta-carotene and intal in inhalations. Both drugs showed antiinflammatory activity reducing the area of alveolitis and emphysema in the lungs, number of neutrophils and lymphocytes in the bronchoalveolar fluid. The experimental data allow to recommend further trial of intal and beta-carotene in granulomatous pulmonary diseases.


Two alanine racemase genes in Salmonella typhimurium that differ in structure and function.
Mutations were isolated in a previously undescribed Salmonella typhimurium gene encoding an alanine racemase essential for utilization of L-alanine as a source of carbon, energy, and nitrogen. This new locus, designated dadB, lies within one kilobase of the D-alanine dehydrogenase locus (dadA), which is also required for alanine catabolism. The dadA and dadB genes are coregulated. Mutants (including insertions) lacking the dadB alanine racemase do not require D-alanine for growth unless a mutation is introduced at a second locus, designated dal. Two genes specifying alanine racemase activity were cloned from S. typhimurium. The two cloned DNA sequences do not cross-hybridize with each other; one was shown to contain the dadB gene.


Role of Ultrasound and CT in the Workup of Right Upper Quadrant Pain in Adults in the Emergency Department: A Retrospective Review of More Than 2800 Cases.
OBJECTIVE. The purpose of this study was to compare ultrasound and CT in the diagnostic evaluation of right upper quadrant pain in adults in the emergency department. MATERIALS AND METHODS. A retrospective review was conducted of adult emergency department encounters for right upper quadrant pain over a 5-year period, excluding those for prior cholecystectomy, current pregnancy, and trauma. Imaging study reports were reviewed for gallbladder and nongallbladder explanations of right upper quadrant pain and were considered positive for cholecystitis when two or more supportive features were present. Encounter outcomes were evaluated on the basis of pathology data and clinical management. RESULTS. Among the encounters, 2859 met the study inclusion criteria, and 18% met the study definition of cholecystitis by pathologic or clinical criteria. The following metrics showed no statistically significant difference between ultrasound and CT, respectively: sensitivity, 61% and 55%; specificity, 91% and 92%; positive predictive value, 63% and 63%; and negative predictive value, 91% and 90%. Both modalities were performed in 20% of encounters. In the subgroup analysis, ultrasound showed an acute nongallbladder abnormality that was missed at a preceding CT examination in only 1 of 238 cases (0.4%). CT showed an acute nongallbladder abnormality missed at a preceding ultrasound examination in 103 of 322 cases (32%). CONCLUSION. CT is noninferior to ultrasound in both ruling in and ruling out the diagnosis of cholecystitis in adult patients undergoing emergency evaluation of right upper quadrant pain and offers the advantage of depicting acute nongallbladder abnormalities.


Glutamatergic Activation of Neuronostatin Neurons in the Periventricular Nucleus of the Hypothalamus.
Neuronostatin, a newly identified anorexigenic peptide, is present in the central nervous system. We tested the hypothesis that neuronostatin neurons are activated by feeding as a peripheral factor and that the glutamatergic system has regulatory influences on neuronostatin neurons. The first set of experiments analyzed the activation of neuronostatin neurons by refeeding as a physiological stimulus and the effectiveness of the glutamatergic system on this physiological stimulation. The subjects were randomly divided into three groups: the fasting group, refeeding group, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)+refeeding group. We found that refeeding increased the phosphorylated signal transducers and transcription activator-5 (pSTAT5) expression in neuronostatin-positive neurons and that the CNQX injection significantly suppressed the number of pSTAT5-expressing neuronostatin neurons. The second set of experiments analyzed the activation pathways of neuronostatin neurons and the regulating effects of the glutamatergic system on neuronostatin neurons. The animals received intraperitoneal injections of glutamate receptor agonists (kainic acid, α-amino-3-hydroxy-5methyl-4-isoazepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA)) or 0.9% NaCl. The number of c-Fos-expressing neuronostatin neurons significantly increased following the AMPA and NMDA injections. In conclusion, we found that the neuronostatin neurons were activated by peripheral or central signals, including food intake and/or glutamatergic innervation, and that the glutamate receptors played an important role in this activation.


Energy flow through the lower extremities in high school baseball pitching.
It is generally accepted that most of the energy transferred to the ball during a baseball pitch is generated in the trunk and lower extremities. Therefore, purpose of this study was to assess the energy flow through the lower extremities during a baseball pitch. It was hypothesised that the (stabilising) leading leg mainly transfers energy in a distal-to-proximal order as a kinetic chain while the (driving) trailing leg generates most energy, primarily at the hip. A joint power analysis was used to determine the rates of energy (power) transfer and generation in the ankles, knees, hips and lumbosacral joint (L5-S1) for 22 youth pitchers. Analyses showed that the leading leg mainly transfers energy upwards in a distal-to-proximal order just before stride foot contact. Furthermore, energy generation was higher in the trailing leg and primarily arose from the trailing hip. In conclusion, the legs contribute differently to the energy flow where the leading leg acts as an initial kinetic chain component and the trailing leg drives the pitch by generating energy. The actions of both legs are combined in the pelvis and passed on to the subsequent, more commonly discussed, open kinetic chain starting at L5-S1.


Intracavity absorption with a continuous wave dye laser: quantification for a narrowband absorber.
Although it is recognized as a very sensitive detection technique, the general application of intracavity absorption to areas such as chemical kinetics and photochemistry has been somewhat limited. Concerns are frequently expressed about the nonlinear nature, experimental difficulty, and reliability of the technique. To allay some of these objections, the dependence of intracavity absorption on factors such as transition strength, concentration, absorber path length, and pump power has been investigated experimentally for a cw dye laser with a narrowband absorber (NO(2)). For this case a Beer-Lambert type relationship has been confirmed over a useful range of these parameters. The extent of intracavity absorption was quantitatively measured directly from the dye laser spectral profiles and, when compared to extracavity measurements, indicated enhancements as high as 12,000 for pump powers near lasing threshold. By defining an intracavity absorption coefficient, it was possible to demonstrate the reliability of the method by obtaining accurate transition strength ratios.


Endoscopic sphincterotomy for stones by experts is safe, even in younger patients with normal ducts.
To provide current information on the risks of endoscopic sphincterotomy for stone. In recent years (since the popularity of laparoscopic cholecystectomy), endoscopic sphincterotomy has been used increasingly for the management of bile duct stones in relatively young and healthy patients. The validity of this trend has been questioned using data on short-term complications derived from earlier decades that involved more elderly and high-risk patients. Seven academic centers collected data prospectively using a common database. Complications within 30 days of the procedures were documented by standard criteria. Of 1921 patients, 112 (5.8%) developed complications; two thirds of these events were graded as mild (<3 days in hospital). There was no evidence of increased risk in younger patients or in those with smaller bile ducts. There was only one severe complication and there were no fatalities in 238 patients age <60, with bile duct diameters of <9 mm. Sphincterotomy for stones can be performed very safely by experienced endoscopists.


Antiphospholipid Antibody Profile Stability Over Time: Prospective Results From the APS ACTION Clinical Database and Repository.
The APS ACTION Registry studies long-term outcomes in persistently antiphospholipid antibody (aPL)-positive patients. Our primary objective was to determine whether clinically meaningful aPL profiles at baseline remain stable over time. Our secondary objectives were to determine (1) whether baseline characteristics differ between patients with stable and unstable aPL profiles, and (2) predictors of unstable aPL profiles over time. A clinically meaningful aPL profile was defined as positive lupus anticoagulant (LAC) test and/or anticardiolipin (aCL)/anti-β2 glycoprotein-I (anti-β2-GPI) IgG/M ≥ 40 U. Stable aPL profile was defined as a clinically meaningful aPL profile in at least two-thirds of follow-up measurements. Generalized linear mixed models with logit link were used for primary objective analysis. Of 472 patients with clinically meaningful aPL profile at baseline (median follow-up 5.1 yrs), 366/472 (78%) patients had stable aPL profiles over time, 54 (11%) unstable, and 52 (11%) inconclusive. Time did not significantly affect odds of maintaining a clinically meaningful aPL profile at follow-up in univariate (P = 0.906) and multivariable analysis (P = 0.790). Baseline triple aPL positivity decreased (OR 0.25, 95% CI 0.10-0.64, P = 0.004) and isolated LAC test positivity increased (OR 3.3, 95% CI 1.53-7.13, P = 0.002) the odds of an unstable aPL profile over time. Approximately 80% of our international cohort patients with clinically meaningful aPL profiles at baseline remain stable at a median follow-up of 5 years; triple aPL-positivity increase the odds of a stable aPL profile. These results will guide future validation studies of stored blood samples through APS ACTION Core Laboratories.


[An intense result contract].
As a consequence of developments in the oral health care profession and in society as a whole horizontally organized oral health care is becoming increasingly widely accepted. For patients, this brings increasing obscurity along with it regarding questions as to whom is responsible for what exactly. In case of conflict it will also become more difficult for lawyers to determine with whom a patient has entered into a (partial) treatment agreement. In order to put an end to such obscurity this article makes a case for legislation prescribing centralized liability for oral health care centres.


Training health professionals in smoking cessation.
There is good evidence that brief interventions from health professionals can increase rates of smoking cessation. A number of trials have examined whether specific skills training for health professionals leads them to have greater success in helping their patients who smoke. The aim of this review was to assess the effectiveness of training health care professionals to deliver smoking cessation interventions to their patients, and to assess the additional effects of prompts and reminders to the health professional to intervene. We searched the Cochrane Tobacco Addiction Group trials register for studies relating to training. Randomised trials in which the intervention was training of health care professionals in smoking cessation. Trials were considered if they reported outcomes for patient smoking rates at least six months after the intervention. We reported on process outcomes, but we excluded trials that reported effects only on process outcomes and not smoking behaviour. We extracted data in duplicate on the type of health professionals, the nature of and duration of the training, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measures were 1. Rates of abstinence from smoking after at least six months follow-up in patients smoking at baseline. 2. Rates of performance of tasks of smoking cessation by health care professionals including offering counselling, setting quit dates, giving follow-up appointments, distributing self-help materials and recommending nicotine gum. Healthcare professionals who had received training were more likely to perform tasks of smoking cessation than untrained controls. Of eight studies that compared patient smoking behaviour between trained professionals and controls, six found no effect of intervention. The effects of training on process outcomes increased if prompts and reminders were used. Training health professionals to provide smoking cessation interventions had a measurable effect on professional performance. There was no strong evidence that it changed smoking behaviour.


The effects of substrates on the optical rotatory dipersion of carnitine acetyltransferase.
1. The optical rotatory dispersion of carnitine acetyltransferase is altered in the presence of l-carnitine or acetyl-l-carnitine. These changes, which include an increase in the reduced mean residue rotation at 233nm. ([M'](233)), suggest that substrate binding causes the enzyme to unfold. 2. CoA and acetyl-CoA have no immediate effect on [M'](233) and CoA has no effect on the change in this parameter induced by l-carnitine. 3. The change in [M'](233) was used as a measure of the degree of saturation of the enzyme with carnitine substrates. Dissociation constants for the enzyme complexes with l-carnitine, d-carnitine and acetyl-l-carnitine were determined in this way. 4. Prolonged incubation of carnitine acetyltransferase in the presence of CoA leads to a small increase in the value of [M'](233) accompanied by irreversible inhibition of the enzyme. 5. Optical-rotatory-dispersion studies of two specifically inhibited enzyme forms are reported.


Usability Testing of Two Mini-Games and One Serious Game to Educate People About Genetics.
The lowering costs of DNA sequencing and the diffusion of numerous Direct to Consumer Genetic Testing (DTC-GT) services have made genetic testing easily available to the general public who can buy them without any medical prescription or consultation. Nevertheless, the knowledge required to understand the provided results and their implications is still scarce in the general public. Starting from these considerations, we developed two mini-games and one serious game to increase people genetic literacy through experiential learning. The three games were tested for usability on a sample of 30 participants, 10 for each game, who were asked to report any positive or negative issue related to the games and to fulfill the Game Experience Questionnaire in order to evaluate their playing experience. Results from the three games show that players experienced moderate levels of immersion and flow, low levels of negative sensations, and a prevalence of positive emotions. In general, these encouraging results suggest that the proposed games are suitable to transmit genetic notions to the general public.


Combining "Bottom-up" and "Top-down" Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC-0941) Pharmacokinetics.
Pictilisib, a weakly basic compound, is an orally administered, potent, and selective pan-inhibitor of phosphatidylinositol 3-kinases for oncology indications. To investigate the significance of high-fat food and gastric pH on pictilisib pharmacokinetics (PK) and enable label recommendations, a dedicated clinical study was conducted in healthy volunteers, whereby both top-down (population PK, PopPK) and bottom-up (physiologically based PK, PBPK) approaches were applied to enhance confidence of recommendation and facilitate the clinical development through scenario simulations. The PopPK model identified food (for absorption rate constant (Ka )) and proton pump inhibitors (PPI, for relative bioavailability (Frel ) and Ka ) as significant covariates. Food and PPI also impacted the variability of Frel . The PBPK model accounted for the supersaturation tendency of pictilisib, and gastric emptying physiology successfully predicted the food and PPI effect on pictilisib absorption. Our research highlights the importance of applying both quantitative approaches to address critical drug development questions.


Disulfide bond structure of the AVR9 elicitor of the fungal tomato pathogen Cladosporium fulvum: evidence for a cystine knot.
Disease resistance in plants is commonly activated by the product of an avirulence (Avr) gene of a pathogen after interaction with the product of a matching resistance (R) gene in the host. In susceptible plants, Avr products might function as virulence or pathogenicity factors. The AVR9 elicitor from the fungus Cladosporium fulvum induces defense responses in tomato plants carrying the Cf-9 resistance gene. This 28-residue beta-sheet AVR9 peptide contains three disulfide bridges, which were identified in this study as Cys2-Cys16, Cys6-Cys19, and Cys12-Cys26. For this purpose, AVR9 was partially reduced, and the thiol groups of newly formed cysteines were modified to prevent reactions with disulfides. After HPLC purification, the partially reduced peptides were sequenced to determine the positions of the modified cysteines, which originated from the reduced disulfide bridge(s). All steps involving molecules with free thiol groups were performed at low pH to suppress disulfide scrambling. For that reason, cysteine modification by N-ethylmaleimide was preferred over modification by iodoacetamide. Upon (partial) reduction of native AVR9, the Cys2-Cys16 bridge opened selectively. The resulting molecule was further reduced to two one-bridge intermediates, which were subsequently completely reduced. The (partially) reduced cysteine-modified AVR9 species showed little or no necrosis-inducing activity, demonstrating the importance of the disulfide bridges for biological activity. Based on peptide length and cysteine spacing, it was previously suggested that AVR9 isa cystine-knotted peptide. Now, we have proven that the bridging pattern of AVR9 is indeed identical to that of cystine-knotted peptides. Moreover, NMR data obtained for AVR9 show that it is structurally closely related to the cystine-knotted carboxypeptidase inhibitor. However, AVR9 does not show any carboxypeptidase inhibiting activity, indicating that the cystine-knot fold is a commonly occurring motif with varying biological functions.


Age-dependent reduction of gamma oscillations in the mouse hippocampus in vitro.
Normal brain ageing is associated with a decline in hippocampal memory functions. Neuronal oscillations in the gamma frequency band have been implicated in various cognitive tasks. In this study we test the effect of normal brain ageing on gamma oscillations in the mouse hippocampus in vitro. gamma Oscillations were evoked by either 10 microM carbachol or 100 nM kainate in ventral hippocampus slices from young (>5 month) and aged (>22 month) C57Bl/J6 mice. In slices from young mice carbachol-induced gamma oscillations were more regular and more coherent than those induced by kainate. Compared with young, the power in the 20-80 Hz frequency range in area CA3 of slices from aged mice was reduced to 14% for kainate-induced oscillations and to 7% for carbachol-induced oscillations, whereas waveform, dominant frequency and coherence of the oscillation were unchanged. Local network properties were assessed by paired-pulse stimulation of Schaffer collateral/commissural fibers. The excitatory synaptic response in stratum radiatum of CA3 was reduced, in correlation with the antidromic population spike, but functional inhibition in CA3 and CA1 was unaffected. Changes in local network properties could not explain the reduced gamma oscillation strength. Since oscillations driven by two different pathways are similarly affected with age, an age-dependent effect on tonic depolarizing drive of principal cells is unlikely to explain the current results. Other mechanisms, including a change with age in the use-dependent modulation of synaptic strength, should account for the impaired gamma oscillations in the aged hippocampus that may contribute to age-dependent memory impairment.


Study of oxidative-stress in rotavirus infected infant mice.
Rotavirus induced diarrhoea was investigated in neonatal mice. Assessment of oxidative/antioxidative profile was the mechanistic approach to study the nature of injury. Neonatal mice (NMRI strain) were infected orally with the homologous strain of (EB) rotavirus (serotype 3). The peak severity of rotavirus infection was attained on the third day post infection. The whole small intestine of neonatal mice on day 3 post infection was homogenized and analysed for oxidative/antioxidative profile. Glutathione and related thiols were significantly declined in rotavirus infected group. Superoxide dismutase, glutathione peroxidase and glutathione-S-transferase (1-chloro 2, 4 dinitrobenzene) activities were also decreased in the rotavirus infected group. The activities of glutathione reductase and glutathione-S-transferase (ethacrynic acid) however were elevated with rotavirus infection in comparison to the control group. Similarly, ADP-FeCI3, NADPH induced lipid peroxidation was elevated with rotavirus infection. Thus the altered oxidative/antioxidative profile indicated the presence of oxidative stress in the rotavirus infected group and can be postulated to have a prominent role in the pathogenesis of the disease.


Adverse events following immunization (AEFI) with the novel influenza a (H1N1) 2009 vaccine: findings from the national registry of all vaccine recipients and AEFI and the passive surveillance system in South Korea.
This study characterized the adverse events following immunization (AEFI) with the novel influenza A (H1N1) 2009 vaccine in Korea. Data on immunization and AEFI were collected between October 27, 2009 and March 15, 2010 through the national immunization registry and passive surveillance systems. The frequency of AEFI and serious adverse events (SAEs) were calculated according to age, sex, priority group, and vaccine type. In 13,758,527 vaccine recipients aged 6 months or older, 2,530 AEFI were reported (18.4 per 100,000 immunizations). The AEFI reporting rate was highest among people aged 10-19 years (29.6 per 100,000 immunizations) and was higher in female recipients than in male recipients (20.0 versus 16.7 per 100,000 immunizations). Most AEFIs were nonspecific systematic reactions that occurred within 24 h (77.4%) after vaccine administration. A total of 178 vaccine-related SAEs were identified, and vaccine-related mortalities were not reported. This study showed that the AEFI reporting rate after influenza A (H1N1) 2009 vaccinations was relatively high, especially in the younger population. Mild systemic reactions accounted for the majority of reported AEFI, and fatal SAEs were rare. This study also implied that passive surveillance might be an efficient safety monitoring system that can detect relatively rare AEFI.


Acetaminophen Metabolite N-Acylphenolamine Induces Analgesia via Transient Receptor Potential Vanilloid 1 Receptors Expressed on the Primary Afferent Terminals of C-fibers in the Spinal Dorsal Horn.
The widely used analgesic acetaminophen is metabolized to N-acylphenolamine, which induces analgesia by acting directly on transient receptor potential vanilloid 1 or cannabinoid 1 receptors in the brain. Although these receptors are also abundant in the spinal cord, no previous studies have reported analgesic effects of acetaminophen or N-acylphenolamine mediated by the spinal cord dorsal horn. We hypothesized that clinical doses of acetaminophen induce analgesia via these spinal mechanisms. We assessed our hypothesis in a rat model using behavioral measures. We also used in vivo and in vitro whole cell patch-clamp recordings of dorsal horn neurons to assess excitatory synaptic transmission. Intravenous acetaminophen decreased peripheral pinch-induced excitatory responses in the dorsal horn (53.1 ± 20.7% of control; n = 10; P < 0.01), while direct application of acetaminophen to the dorsal horn did not reduce these responses. Direct application of N-acylphenolamine decreased the amplitudes of monosynaptic excitatory postsynaptic currents evoked by C-fiber stimulation (control, 462.5 ± 197.5 pA; N-acylphenolamine, 272.5 ± 134.5 pA; n = 10; P = 0.022) but not those evoked by stimulation of Aδ-fibers. These phenomena were mediated by transient receptor potential vanilloid 1 receptors, but not cannabinoid 1 receptors. The analgesic effects of acetaminophen and N-acylphenolamine were stronger in rats experiencing an inflammatory pain model compared to naïve rats. Our results suggest that the acetaminophen metabolite N-acylphenolamine induces analgesia directly via transient receptor potential vanilloid 1 receptors expressed on central terminals of C-fibers in the spinal dorsal horn and leads to conduction block, shunt currents, and desensitization of these fibers.


Localization of temporal lobe foci by ictal EEG patterns.
Identifying patients whose complex partial seizures originate in temporal neocortex rather than in hippocampus is important because such patients have less favorable outcomes with standard anteromesial temporal resections. We reviewed scalp-recorded ictal EEGs of 93 epilepsy surgery candidates who either underwent intracranial EEG monitoring (n = 58) or who were referred directly for temporal lobectomy (n = 35). We definded seven patterns of early seizure discharges, grouped patients according to their seizure pattern, and correlated these with the site of seizure onset determined by intracranial EEG. Categorization by seizure pattern was also compared with brain magnetic resonance imaging (MRI) findings intracarotid amobarbital (Wada) testing. An initial, regular 5- to 9- Hz inferotemporal rhythm (type 1A) was most specific for hippocampal-onset seizures. Less commonly, a similar vertex/parasagittal positive rhythm (type 1B) or a combination of types 1B and 1A rhythms (type 1C) was recorded. Seizures originating in temporal neocortex were most often associated with irregular, polymorphic, 2- to 5-Hz lateralized activity (type 2A). This pattern was commonly followed by a type 1A theta rhythm (type 2B) or was preceded by repetitive, sometimes periodic, sharp waves (type 2C). Seizures without a clear lateralized EEG discharge (type 3) were most commonly of temporal neocortical origin. These associations between type of seizure pattern and probable site of cerebral origin were statistically significant. MRI and Wada testing did not have as much specificity as ictal patterns in differentiating among seizure origins. We conclude that the initial pattern of ictal discharge on scalp EEG can assist in distinguishing seizures of temporal neocortical onset from those of hippocampal onset. This information can be used to identify patients for invasive monitoring.


Chronic Cerebral Hypoperfusion Activates the Coagulation and Complement Cascades in Alzheimer's Disease Mice.
Alzheimer's disease (AD) in the elderly is frequently accompanied by chronic cerebral hypoperfusion (CCH), which impairs the clearance of amyloid beta (Aβ) due to the dysfunction of the blood-brain barrier (BBB) and accelerates the AD pathology. Since the coagulation and complement cascades are associated with BBB dysfunction and AD pathology, we investigated the expression changes of coagulation (fibrinogen alpha chain-FGA, coagulation factor XIII A chain-Factor XIIIα) and complement (plasma protease C1 inhibitor-C1-INH, Complement component 3-C3) factors in the brain of novel AD model (APP23) mice with CCH at 12 months of age. Immunohistochemical and immunofluorescent analysis showed that the expressions of FGA, Factor XIIIα, C1-INH and C3 were significantly increased in cerebral neocortex, hippocampus, and thalamus of APP23 + CCH group (n = 12) as compared with wild type (WT, n = 10) and APP23 (n = 10) groups (⁎P < .05 and ⁎⁎P < .01 vs WT; #P < .05 and ##P < .01 vs APP23), especially near and inside of neurovascular unit. The present study suggests that CCH activated both the coagulation and complement cascades in a novel AD model mice brain accompanied by the acceleration of AD pathology.


Yeast and mammalian metallothioneins functionally substitute for yeast copper-zinc superoxide dismutase.
Copper-zinc superoxide dismutase catalyzes the disproportionation of superoxide anion to hydrogen peroxide and dioxygen and is thought to play an important role in protecting cells from oxygen toxicity. Saccharomyces cerevisiae strains lacking copper-zinc superoxide dismutase, which is encoded by the SOD1 gene, are sensitive to oxidative stress and exhibit a variety of growth defects including hypersensitivity to dioxygen and to superoxide-generating drugs such as paraquat. We have found that in addition to these known phenotypes, SOD1-deletion strains fail to grow on agar containing the respiratory carbon source lactate. We demonstrate here that expression of the yeast or monkey metallothionein proteins in the presence of copper suppresses the lactate growth defect and some other phenotypes associated with SOD1-deletion strains, indicating that copper metallothioneins substitute for copper-zinc superoxide dismutase in vivo to protect cells from oxygen toxicity. Consistent with these results, we show that yeast metallothionein mRNA levels are dramatically elevated under conditions of oxidative stress. Furthermore, in vitro assays demonstrate that yeast metallothionein, purified or from whole-cell extracts, exhibits copper-dependent antioxidant activity. Taken together, these data suggest that both yeast and mammalian metallothioneins may play a direct role in the cellular defense against oxidative stress by functioning as antioxidants.


Validation of the Short Version (TLS-15) of the Triangular Love Scale (TLS-45) across 37 Languages.
Love is a phenomenon that occurs across the world and affects many aspects of human life, including the choice of, and process of bonding with, a romantic partner. Thus, developing a reliable and valid measure of love experiences is crucial. One of the most popular tools to quantify love is Sternberg's 45-item Triangular Love Scale (TLS-45), which measures three love components: intimacy, passion, and commitment. However, our literature review reveals that most studies (64%) use a broad variety of shortened versions of the TLS-45. Here, aiming to achieve scientific consensus and improve the reliability, comparability, and generalizability of results across studies, we developed a short version of the scale-the TLS-15-comprised of 15 items with 5-point, rather than 9-point, response scales. In Study 1 (N = 7,332), we re-analyzed secondary data from a large-scale multinational study that validated the original TLS-45 to establish whether the scale could be truncated. In Study 2 (N = 307), we provided evidence for the three-factor structure of the TLS-15 and its reliability. Study 3 (N = 413) confirmed convergent validity and test-retest stability of the TLS-15. Study 4 (N = 60,311) presented a large-scale validation across 37 linguistic versions of the TLS-15 on a cross-cultural sample spanning every continent of the globe. The overall results provide support for the reliability, validity, and cross-cultural invariance of the TLS-15, which can be used as a measure of love components-either separately or jointly as a three-factor measure.


Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates TLR9-Mediated Innate Immune Responses.
TLRs are distributed in their characteristic cellular or subcellular compartments to efficiently recognize specific ligands and to initiate intracellular signaling. Whereas TLRs recognizing pathogen-associated lipids or proteins are localized to the cell surface, nucleic acid-sensing TLRs are expressed in endosomes and lysosomes. Several endoplasmic reticulum (ER)-resident proteins are known to regulate the trafficking of TLRs to the specific cellular compartments, thus playing important roles in the initiation of innate immune responses. In this study, we show that an ER-resident protein, Nogo-B (or RTN4-B), is necessary for immune responses triggered by nucleic acid-sensing TLRs, and that a newly identified Nogo-B-binding protein (glucosyltransferases, Rab-like GTPase activators and myotubularins [GRAM] domain containing 4 [GRAMD4]) negatively regulates the responses. Production of inflammatory cytokines in vitro by macrophages stimulated with CpG-B oligonucleotides or polyinosinic:polycytidylic acid was attenuated in the absence of Nogo-B, which was also confirmed in serum samples from Nogo-deficient mice injected with polyinosinic:polycytidylic acid. Although a deficiency of Nogo-B did not change the incorporation or delivery of CpG to endosomes, the localization of TLR9 to endolysosomes was found to be impaired. We identified GRAMD4 as a downmodulator for TLR9 response with a Nogo-B binding ability in ER, because our knockdown and overexpression experiments indicated that GRAMD4 suppresses the TLR9 response and knockdown of Gramd4 strongly enhanced the response in the absence of Nogo-B. Our findings indicate a critical role of Nogo-B and GRAMD4 in trafficking of TLR9.


Understanding Girls' Motivation to Participate in Sport: The Effects of Social Identity and Physical Self-Concept.
Introduction: Girls are often less motivated to participate in community sport compared to boys. Having a strong social identity with a sports team is positively associated with motivation to continue participation in sport, yet the mechanisms explaining this association are not well-known. In the current study, physical self-concept is tested as a mediator of the association between social identity and motivation. Method: Girl badminton athletes were recruited to examine how the team environment shapes physical self-concept, and whether this association relates to motivation to participate in sport. Ninety-two girls completed a self-report survey to measure social identity, physical self-perceptions, and motivation. Two mediation models were conducted to examine whether physical self-concept mediated the relationship between social identity and autonomous motivation and controlled motivation. Results: Physical self-concept partially mediated the relationship between social identity and autonomous motivation. The bootstrapped unstandardized indirect effect was, b = 0.05, 95% CI = 0.002 to.14. Physical self-concept fully mediated the relationship between social identity and controlled motivation. The bootstrapped unstandardized indirect effect was, b = -0.13, 95% CI = -0.30 to -0.01, p = 0.04. Discussion: These results highlight the importance of the group context in relation to individual physical self-concept and motivation. Overall, targeting aspects of the team environment in community-level sport may be an important strategy to improve girls' physical self-concept, and autonomous motivation to continue sport participation.


A Technique for Safe Redo Sternotomy in Patients with Aortic Proximity to the Sternum.
The risk of redo sternotomy is greatly elevated in the setting of aortic proximity to the sternum. Current strategies to avoid catastrophic neurologic injury upon sternal reentry include establishment of peripheral bypass with the use of deep hypothermia and low-flow bypass, both of which may increase risk of neurologic complications. Here, we describe a technique for safe sternal reentry and illustrate its successful use in a patient with close proximity of the aorta to the sternum. With this technique, peripheral cardiopulmonary bypass is established prior to sternal reentry via cannulation of the right axillary artery and femoral vein, and the patient is cooled as the innominate artery is dissected, mobilized, and controlled. This permits the rapid institution of selective antegrade cerebral perfusion (SACP) in the event of aortic injury during sternal reentry. Once the innominate artery is isolated and SACP is initiated, one can safely complete the redo sternotomy, dissection, and distal ascending aortic cross-clamping to continue the operation without interruption in cerebral blood flow. This technique offers a safe approach in select patients and should be utilized in similar high-risk cases.


Cardiac remodeling secondary to chronic volume overload is attenuated by a novel MMP9/2 blocking antibody.
Monoclonal antibody derivatives are promising drugs for the treatment of various diseases due to their high matrix metalloproteinases (MMP) active site specificity. We studied the effects of a novel antibody, SDS3, which specifically recognizes the mature active site of MMP9/2 during ventricular remodeling progression in a mouse model of chronic volume overload (VO). VO was induced by creating an aortocaval fistula (ACF) in 10- to 12-week-old C57BL male mice. The VO-induced mice were treated with either vehicle control (PBS) or with SDS3 twice weekly by intraperitoneal (ip) injection. The relative changes in cardiac parameters between baseline (day 1) and end-point (day 30), were evaluated by echocardiography. The effects of SDS3 treatment on cardiac fibrosis, cardiomyocyte volume, and cardiac inflammation were tested by cardiac staining with Masson's trichrome, wheat Germ Agglutinin (WGA), and CD45, respectively. Serum levels of TNFα and IL-6 with and without SDS3 treatment were tested by ELISA. SDS3 significantly reduced cardiac dilatation, left ventricular (LV) mass, and cardiomyocyte hypertrophy compared to the vehicle treated animals. The antibody also reduced the heart-to-body weight ratio of the ACF animals to values comparable to those of the controls. Interestingly, the SDS3 group underwent significant reduction of cardiac inflammation and pro-inflammatory cytokine production, indicating a regulatory role for MMP9/2 in tissue remodeling, possibly by tumor necrosis factor alpha (TNFα) activation. In addition, significant changes in the expression of proteins related to mitochondrial function were observed in ACF animals, these changes were reversed following treatment with SDS3. The data suggest that MMP9/2 blockage with SDS3 attenuates myocardial remodeling associated with chronic VO by three potential pathways: downregulating the extracellular matrix proteolytic cleavage, reducing the cardiac inflammatory responses, and preserving the cardiac mitochondrial structure and function.


Random forests, a novel approach for discrimination of fish populations using parasites as biological tags.
Due to the complexity of host-parasite relationships, discrimination between fish populations using parasites as biological tags is difficult. This study introduces, to our knowledge for the first time, random forests (RF) as a new modelling technique in the application of parasite community data as biological markers for population assignment of fish. This novel approach is applied to a dataset with a complex structure comprising 763 parasite infracommunities in population samples of Atlantic cod, Gadus morhua, from the spawning/feeding areas in five regions in the North East Atlantic (Baltic, Celtic, Irish and North seas and Icelandic waters). The learning behaviour of RF is evaluated in comparison with two other algorithms applied to class assignment problems, the linear discriminant function analysis (LDA) and artificial neural networks (ANN). The three algorithms are used to develop predictive models applying three cross-validation procedures in a series of experiments (252 models in total). The comparative approach to RF, LDA and ANN algorithms applied to the same datasets demonstrates the competitive potential of RF for developing predictive models since RF exhibited better accuracy of prediction and outperformed LDA and ANN in the assignment of fish to their regions of sampling using parasite community data. The comparative analyses and the validation experiment with a 'blind' sample confirmed that RF models performed more effectively with a large and diverse training set and a large number of variables. The discrimination results obtained for a migratory fish species with largely overlapping parasite communities reflects the high potential of RF for developing predictive models using data that are both complex and noisy, and indicates that it is a promising tool for parasite tag studies. Our results suggest that parasite community data can be used successfully to discriminate individual cod from the five different regions of the North East Atlantic studied using RF.


Bacteriophage therapy for control of necrotic enteritis of broiler chickens experimentally infected with Clostridium perfringens.
Several lytic bacteriophages effective at destroying a genetically diverse population of Clostridium perfringens were isolated from the environment, extensively characterized, and used to formulate a multivalent bacteriophage cocktail designated -401." Two in vivo studies were conducted to determine the cocktail's efficacy in controlling necrotic enteritis (NE) caused by C. perfringens. The first study investigated the efficacy of INT-401 and a bacteriophage-derived, toxoid-type vaccine in controlling NE in C. perfringens-challenged broiler chickens. The study was designed as a proof-of-concept battery cage study with birds reared until 28 days old. Compared with the mortality observed with the C. perfringens-challenged but untreated chickens, oral administration of INT-401 significantly (P < 0.05) reduced the mortality of the C. perfringens-challenged birds by 92%. Overall, INT-401 was more effective than the toxoid vaccine in controlling active C. perfringens infection. The second study was conducted to investigate the effectiveness of the cocktail when administered via oral gavage, feed, or drinking water. The study was conducted in floor pens, with birds reared to 42 days old. INT-401 administered by all three methods significantly (P < 0.05) reduced mortality. Weight gain and feed conversion ratios were significantly better in the C, perfringens-challenged chickens treated with INT-401 than in the C. perfringens-challenged, phage-untreated control birds. The data indicate that delivering INT-401 to broiler chickens via their drinking water or feed may be an effective means for controlling NE caused by C. perfringens and may improve weight gain and feed conversion ratios in birds with clinical or subclinical NE.


Evaluation of Hindlimb Deformity and Posture in Dogs with Grade 2 Medial Patellar Luxation during Awake Computed Tomography Imaging while Standing.
The aim of this study was to determine the degree of bone deformities and hindlimb postural abnormalities in a standing position in awake Toy poodles with and without grade 2 medial patellar luxation (MPL) using high speed 320-row computed tomography (CT). The limbs with grade 2 MPL (MPL-G2 group) and without any orthopaedic disorders (control group) were imaged in a standing position, without sedation or anaesthesia, using CT. In MPL-G2 group, images were obtained when the patella was luxated (G2-L group) and reduced (non-luxation, G2-NL group). Bone morphologies of the femur and tibia were quantified three-dimensionally. Hindlimb standing posture was evaluated by measuring femoral rotation and abduction angles, tibial rotation angle, metatarsal rotation angle, foot rotation angle, angle between the femoral anatomical axis and the mechanical axis of hindlimb and stifle joint line convergence angle. There were no significant differences in bone morphologic parameters between the MPL-G2 group (5 limbs) and the control group (6 limbs). In the G2-NL group, there were no significant hindlimb postural abnormalities. In contrast, in the G2-L group, significant hindlimb postural abnormalities including external rotation of femur, internal rotation of tibia and foot, external rotation of tarsal joint, large stifle joint convergence angle, genu varum and toe-in standing were observed. Dogs with grade 2 MPL have no bone deformities but show abnormal standing posture when the patella is luxated.


Heroin self-administration: I. Incubation of goal-directed behavior in rats.
This study used heroin self-administration to investigate incubation of goal-directed heroin-seeking behavior following abstinence. Male Sprague-Dawley rats self-administered heroin on a fixed ratio 10 (FR10) schedule of reinforcement with licking of an empty spout serving as the operant behavior during 14 daily 3 h sessions. After this acquisition period, all rats received a 90 min extinction session following either 1 day or 14 days of home cage abstinence. When the extinction session occurred after only 1 day of home cage abstinence, rats with a history of heroin self-administration divided their responses equally between the previously "active" and "inactive" spouts. However, when the extinction session occurred following 14 days of home cage abstinence, the rats exhibited marked goal-directed heroin-seeking behavior by licking more on the previously "active" than "inactive" spout. These findings demonstrate that heroin-seeking behavior incubates over time, resulting in goal-directed heroin-seeking behavior in rats following 14 days but not 1 day of abstinence. Moreover, this facilitatory effect occurred in response to a different training schedule, lower total drug intake, and shorter periods of daily access than previously reported with heroin.


Application of the electro-Fenton process for cutting fluid mineralization.
Organic compound is the main pollutant in industrial effluent. Conventional wastewater treatment processes are inefficient for the removal of toxic or non-biodegradable organic pollutants. Advanced electrochemical depollution is a very efficient and economic method, suitable when the wastewater contains toxic and recalcitrant organic pollutants. The aim of the present study was to investigate the application of the electro-Fenton (EF) process for the degradation and mineralization of a stable oil-in-water emulsion (0.01% in v/v). The effects of operating parameters such as cathode material (graphite, Ti/Pt and steel), nature (Na2SO4, NaNO3 and NaCl) and dose of electrolyte (25-75 mM), initial ferrous ions concentration (1-75 mM), current intensity (0.1-0.2 A) and operating time, on chemical oxygen demand (COD) removal efficiency, were studied. Results showed that the EF method can be used efficiently for the degradation of stable cutting oil emulsion. For considered initial conditions (bubbling compressed air at 1 L/min, 0.15 A, pH 3, [Na2SO4]=0.05 M, [FeSO4]=0.015 M, COD0=400 mg O2/L), the best removal efficiencies were obtained under the following conditions: graphite as cathode material, 180 min for treatment duration and 0.05 M [Na2SO4]. For these conditions, treatment of 250 mL of emulsion led to 93.6% of cutting fluid mineralization, which correspond to 25 mg O2/L of final COD, 19 kWh/m3 of treated wastewater and 24.039 kWh/kg of COD removal.


Comparison of optical resolution with digital and standard fiberoptic cystoscopes in an in vitro model.
To compare two different distal sensor flexible endoscopes with standard fiberoptic cystoscopes for optical resolution. Distal video sensor flexible endoscopy may represent the cusp of a new endoscopic revolution. Twenty-three participants evaluated the optical resolution capabilities of six flexible cystoscopes. The two presently available distal sensor flexible cystoscopes, ACMI DCN-2010 digital flexible cystoscope and Olympus CYF-V EndoEYE flexible video cystoscope, were compared with the four leading fiberoptic cystoscopes, ACMI ACN-2 fiberoptic cystoscope, Olympus CYF-4 Cystofiberscope, Karl Storz 11272CU1 Flexible Cystoscope, and Richard Wolf Flexible Fibre Urethro-Cystoscope, in an in vitro model. The participants recorded the numerical digits they were able to visualize through five solutions with progressively increasing concentrations of hematoxylin dye (C1 to C5). The cystoscopic images were viewed on a 13-in. medical grade Olympus monitor with an Olympus Visera camera system. No differences were detected among the cystoscopes at the lowest concentrations of hematoxylin dye (C1 and C2). At C3 to C5, the mean percentage of visualized numbers for the ACMI and Olympus distal sensor flexible cystoscopes was significantly greater than for all fiberoptic cystoscopes (P <0.01). At the highest concentration (C5), the ACMI distal sensor cystoscope performed significantly better than did the Olympus distal sensor flexible cystoscopes (P <0.01), although at all other concentrations, the two digital video cystoscopes performed equivalently. The results of this in vitro study suggest that cystoscopes with distal sensor technology improve visibility in a simulated challenging working environment compared with fiberoptic cystoscopes.


Occupational therapy practice patterns with older Swedish persons at home.
This paper explores and describes occupational therapy practice patterns during two periods for 89 elderly persons living at home. Occupational therapists working in one social welfare district in Stockholm, Sweden documented and reported every occupational therapy intervention provided. The results revealed that the elderly persons who received occupational therapy services during an extended period had an age span of 30 years, with a mean age over 80 years. They had several medical problems and were living in different types of settings. Occupational therapists provided a wide range of interventions, most frequently categorised as treatment, especially related to leisure activities. Irrespective of level of care, the median of interventions per person increased or was the same over time, and 72% of the elderly persons remained at the same level of care. Enabling occupation for elderly disabled person living in their home involves constantly adjusting to the current situation since the clients' capacities, goals and environment change over time. Therefore, occupational therapists need to have a client-centred approach working in home health community services.


[The spontaneous activity of the perivesical area of the ureter].
Electrical activity of the ureter pericystic region was found to have a definite own rhythm. Noradrenaline and adrenaline were able to induce rhythmic activity in previously inactive pericystic areas. The existence of pacemaker area in the ureter pericystic region seems to act as an additional system for coordination of polarity of the excitation-contractile waves.


Ultrasonic output measurements of multiple-mode diagnostic ultrasound systems.
Electronic control has brought unprecedented flexibility and complexity in the variety of ultrasonic signals and beams available from a single modern multiple-mode ultrasonic imaging system. The process of measuring the ultrasonic output of these systems is started with the identification of relevant system parameters. Because the combinations of control settings for these parameters can number in the tens of thousands for some of the newer systems, a rational methodology for finding the highest global intensity or pressure values was necessary. To aid in the search, a linear simulation model was developed to predict those control settings that produce the highest relative intensity and pressure levels and their peak locations. This information became the starting point for actual measurements. An equipment setup suitable for multimode measurements is described. Experimental mapping procedures were used to find actual global maxima by varying a smaller subset of control parameters. Data were checked by formulae derived specifically for multimode measurements.


Nasal eosinophilia and serum soluble intercellular adhesion molecule 1 in patients with allergic rhinitis treated with montelukast alone or in combination with desloratadine or levocetirizine.
Because intercellular adhesion molecule (ICAM) 1 and recruitment of eosinophils are crucial in supporting allergic inflammation, their down-regulation may bring additional benefits in patients' recovery. We have assessed nasal eosinophilia and serum soluble ICAM-1 (sICAM-1) concentrations in relation to nasal symptoms in patients with persistent allergic rhinitis (AR) treated for 6 weeks with either desloratadine, levocetirizine, montelukast alone, or in combination. In this single-center, randomized, double-blind, placebo-controlled, crossover, two-arm study, 40 patients with persistent AR were randomized to receive either montelukast and/or levocetirizine or placebo (n = 20) or to receive treatment with montelukast and/or desloratadine or placebo (n = 20). Nasal eosinophilia and concentration of sICAM-1 in peripheral blood were assessed before and on the last day of each treatment period. All active treatments in both arms of the study resulted in the decrease of sICAM-1 and nasal eosinophilia, which correlated with the severity of nasal symptoms. In the montelukast/levocetirizine arm, montelukast decreased nasal eosinophilia more significantly than levocetirizine, whereas in reduction of sICAM-1 all active treatment options were equally effective. However, in the desloratadine/montelukast arm, the resulting improvement of combination therapy of sICAM-1 and the influx of eosinophils was not statistically significant. The improvement of nasal symptoms in patients with AR treated with antihistamines, with or without montelukast, may additionally result from the reduction of sICAM-1 and nasal eosinophilia. Because the combination therapy may bring inconclusive benefits in this area there is a strong need of further studies to find mechanisms that favor combination therapy.


Small bowel disease prevalence on video capsule endoscopy in chronic granulomatous disease-associated inflammatory bowel disease.
Patients with chronic granulomatous disease (CGD) may develop inflammatory bowel disease (IBD). Characterization of small bowel disease in this cohort is scarce. Here, we sought to determine the prevalence and characteristics of small bowel disease and evaluate the clinical utility of video capsule endoscopy (VCE) for its diagnosis. A retrospective study was performed on patients with CGD who were evaluated for gastrointestinal disease with VCE as a part of ongoing natural history studies at a single academic center. VCEs were reviewed for inflammatory findings and severity of disease utilizing the Capsule Endoscopy Crohn's Disease Activity Index. Radiographic studies and endoscopies performed within 30 days of VCE were compared with small bowel inflammatory findings. Twenty-six VCEs corresponding to 25 patients were found. The majority of patients were male and White; mean age was 28 years old. The majority (85%) demonstrated presence of small bowel inflammatory findings on VCE including strictures, ulcers, erosions, and erythema. Duodenal and ileal inflammatory disease on endoscopy did not correlate with disease on VCE. Moderate-severe colonic disease correlated with moderate-severe disease on VCE. Radiography did not correlate with disease on VCE. Prolonged small bowel transit time correlated with moderate-severe small bowel disease. Small bowel IBD was highly prevalent in this cohort of patients with CGD. Limitations included small sample size. Given that radiology and duodenal/ileal disease did not correlate with VCE findings, VCE-driven investigation of small bowel disease should be considered in patients with CGD-associated IBD, particularly those with colonic disease.


Quantitative microinjection of trehalose into mouse oocytes and zygotes, and its effect on development.
Sugars such as trehalose are effectively used by various organisms as protective agents to undergo anhydrobiosis and cryobiosis. The objective of this study was first to establish a method for quantitative delivery of trehalose as a model sugar into oocytes, and then to evaluate its effect on development of mouse zygotes. To this end, a quantitative microinjection technique was developed using volumetric response of microdroplets suspended in dimethylpolysilaxene. To verify accuracy of this technique, both microdroplets and oocytes were microinjected with fluorophore-labeled dextran. Thereafter, injection volumes were calculated from fluorescence intensity, and volumetric responses of both microdroplets and oocytes. Comparison of calculated injection volumes revealed that this technique reflects microinjection into oocytes with pL-accuracy. The next series of experiments focused on toxicity of injection buffers (i.e., 10mM Tris and 15mM Hepes) and trehalose. Microinjection of Hepes and Tris buffer in the presence of 0.1M trehalose resulted in blastocyst rates of 86 and 72%, respectively, without a significant difference when compared to controls (86%). In subsequent experiments, Hepes was used as the injection buffer, and embryonic development of zygotes was studied as a function of intracellular trehalose concentrations. Microinjection of trehalose up to 0.15M resulted in development to blastocyst stage similar to controls (85 and 87%, respectively) while the blastocyst rate was significantly decreased (43%) in the presence of 0.20M intracellular trehalose. When transferred to foster mothers, trehalose-injected zygotes (0.1M) implanted and developed to day 16 fetuses similar to controls, healthy pups were born. The findings of this study suggest that trehalose at effective intracellular concentrations does not impair development of mouse zygotes.


Deep learning approach to assess damage mechanics of bone tissue.
Machine learning methods have the potential to transform imaging techniques and analysis for healthcare applications with automation, making diagnostics and treatment more accurate and efficient, as well as to provide mechanistic insights into tissue deformation and fracture in physiological and pathological conditions. Here we report an exploratory investigation for the classification and prediction of mechanical states of cortical and trabecular bone tissue using convolutional neural networks (CNNs), residual neural networks (ResNet), and transfer learning applied to a novel dataset derived from high-resolution synchrotron-radiation micro-computed tomography (SR-microCT) images acquired in uniaxial continuous compression in situ. We present the systematic optimization of CNN architectures for classification of this dataset, visualization of class-defining features detected by the CNNs using gradient class activation maps (Grad-CAMs), comparison of CNN performance with ResNet and transfer learning models, and perhaps most critically, the challenges that arose from applying machine learning methods to an experimentally-derived dataset for the first time. With optimized CNN architectures, we obtained trained models that classified novel images between failed and pristine classes with over 98% accuracy for cortical bone and over 90% accuracy for trabecular bone. Harnessing a pre-trained ResNet with transfer learning, we further achieved over 98% accuracy on the cortical dataset, and 99% on the trabecular dataset. This demonstrates that powerful classifiers for high-resolution SR-microCT images can be developed even with few unique training samples and invites further development through the inclusion of more data and training methods to move towards novel, fundamental, and machine learning-driven insights into microstructural states and properties of bone.


Aging under Pressure: The Roles of Reactive Oxygen and Nitrogen Species (RONS) Production and Aging Skeletal Muscle in Endothelial Function and Hypertension-From Biological Processes to Potential Interventions.
The proportion of adults living with hypertension increases significantly with advancing age. It is therefore important to consider how health and vitality can be maintained by the aging population until end of life. A primary risk factor for the progression of cardiovascular diseases (CVD) is hypertension, so exploring the factors and processes central to this burden of disease is essential for healthy aging. A loss of skeletal muscle quantity and quality is characteristic in normal aging, with a reduction of vasodilatory capacity caused by endothelial dysfunction, and subsequent increase in peripheral resistance and risk for hypertension. Reactive Oxygen and Nitrogen Species (RONS) encompass the reactive derivatives of NO and superoxide, which are continuously generated in contracting skeletal muscle and are essential mediators for cellular metabolism. They act together as intra and intercellular messengers, gene expression regulators, and induce programmed cell death. In excessive amounts RONS can inflict damage to endothelial and skeletal muscle cells, alter signaling pathways or prematurely promote stress responses and potentially speed up the aging process. The age-related increase in RONS by skeletal muscle and endothelial mitochondria leads to impaired production of NO, resulting in vascular changes and endothelial dysfunction. Changes in vascular morphology is an early occurrence in the etiology of CVDs and, while this is also a normal characteristic of aging, whether it is a cause or a consequence of aging in hypertension remains unclear. This review serves to focus on the roles and mechanisms of biological processes central to hypertension and CVD, with a specific focus on the effects of aging muscle and RONS production, as well as the influence of established and more novel interventions to mediate the increasing risk for hypertension and CVD and improve health outcomes as we age.


Energy evaluation of β-strand packing in a fibril-forming SH3 domain.
We examine the energetics of β-strand packing in a fibril-forming SH3 domain using a simple sequence-based energy model. First, we describe this packing energy function and then apply it to three model systems: Aβ, HET-s prion, and SH3 domain. The packing results of Aβ and HET-s are compared to and are consistent with available experimental and computational results. Moreover, our results show that a native β-strand in SH3 is strongly disfavored to pack with any other strand, in accord with recent NMR data. Finally, based on packing energy calculations, several SH3 models of β-strand packing are proposed that fit well with known electron microscopy maps.


Physician self-audit: a scoping review.
Self-audit involves self-collection of personal performance data, reflection on gaps between performance and standards, and development and implementation of learning or quality improvement plans by individual care providers. It appears to stimulate learning and quality improvement, but few physicians engage in self-audit. The purpose of this study was to identify how self-audit has been operationalized; factors influencing self-audit conduct and outcomes, including program design; and issues warranting further research. A systematic review of quantitative and qualitative studies was undertaken. Two individuals independently reviewed searches of indexed literature databases, tables of contents, and references of eligible studies. Data were extracted and tabulated to describe the nature and impact of self-audit programs. Six studies evaluated the impact of self-audit programs. No program was based on a model or theory that informed its design. All studies showed improved compliance with care delivery guidelines and/or improved patient outcomes, although these findings were largely self-reported. Programs varied so features associated with benefit could not be identified. Overall there is a need for guidance on all aspects of self-audit for both participants and leaders. This guidance would be useful to educators, professional associations, and medical certification bodies to plan, develop, implement, evaluate, and support self-audit programs. Further research should aim at developing training programs and tools that address and evaluate a variety of competencies across different disciplines using more rigorous research designs, including both quantitative and qualitative approaches.


Immune defence under extreme ambient temperature.
Owing to global climate change, the extreme weather conditions are predicted to become more frequent, which is suggested to have an even greater impact on ecological interactions than the gradual increase in average temperatures. Here, we examined whether exposure to high ambient temperature affects immune function of the great pond snail (Lymnaea stagnalis). We quantified the levels of several immune traits from snails maintained in a non-stressful temperature (15°C) and in an extreme temperature (30°C) that occurs in small ponds during hot summers. We found that snails exposed to high temperature had weaker immune defence, which potentially predisposes them to infections. However, while phenoloxidase and antibacterial activity of snail haemolymph were reduced at high temperature, haemocyte concentration was not affected. This suggests that the effect of high temperature on snail susceptibility to infections may vary across different pathogens because different components of invertebrate immune defence have different roles in resistance.


[Antibiotic treatment of cystic fibrosis].
Lower respiratory tract superinfection is nearly constant in cystic fibrosis and has a significant impact on mortality. The three organisms which most often colonize the bronchial tree are Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. The latter organism is found in 70% to 90% of older cystic fibrosis patients. P. aeruginosa infections are remarkably persistent and cause severe, extensive lung damage. Antimicrobial therapy is indicated in patients with clinical symptoms (fever, weight loss, changes in sputum and auscultation) and should be selected on the basis of cytobacteriologic studies of sputum. Oral antibiotics are usually successful in eradicating S. aureus and H. influenzae. Conversely, intravenous therapy is required in most cases of P. aeruginosa infection. Fifteen-day courses are given repeatedly, either on a routine basis every three months, or whenever new clinical symptoms develop. Antimicrobials usually fail to eradicate P. aeruginosa even when significant clinical improvement occurs. Two-drug therapy and judicious use of the various available anti-microbial agents should delay development of resistant strains, an event which is nearly inevitable as antimicrobial treatments are repeated.