The anatomy of pain and suffering in the brain and its clinical implications.
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Chronic pain, with a prevalence of 20-30 % is the major cause of human suffering worldwide, because effective, specific and safe therapies have yet to be developed. It is unevenly distributed among sexes, with women experiencing more pain and suffering. Chronic pain can be anatomically and phenomenologically dissected into three separable but interacting pathways, a lateral 'painfulness' pathway, a medial 'suffering' pathway and a descending pain inhibitory pathway. One may have pain(fullness) without suffering and suffering without pain(fullness). Pain sensation leads to suffering via a cognitive, emotional and autonomic processing, and is expressed as anger, fear, frustration, anxiety and depression. The medial pathway overlaps with the salience and stress networks, explaining that behavioural relevance or meaning determines the suffering associated with painfulness. Genetic and epigenetic influences trigger chronic neuroinflammatory changes which are involved in transitioning from acute to chronic pain. Based on the concept of the Bayesian brain, pain (and suffering) can be regarded as the consequence of an imbalance between the two ascending and the descending pain inhibitory pathways under control of the reward system. The therapeutic clinical implications of this simple pain model are obvious. After categorizing the working mechanisms of each of the available treatments (pain killers, psychopharmacology, psychotherapy, neuromodulation, psychosurgery, spinal cord stimulation) to 1 or more of the 3 pathways, a rational combination can be proposed of activating the descending pain inhibitory pathway in combination with inhibition of the medial and lateral pathway, so as to rebalance the pain (and suffering) pathways.


Identification of a conformational heparin-recognition motif on the peptide hormone secretin: key role for cell surface binding.
Secretin is a peptide hormone that exerts pleiotropic physiological functions by specifically binding to its cognate membrane-bound receptor. The membrane catalysis model of peptide-receptor interactions states that soluble peptidic ligands initially interact with the plasma membrane. This interaction increases the local concentration and structures the peptide, enhancing the rate of receptor binding. However, this model does not consider the dense network of glycosaminoglycans (GAGs) at the surface of eukaryotic cells. These sulfated polysaccharide chains are known to sequester numerous proteic signaling molecules. In the present study, we evaluated the interaction between the peptide hormone secretin and sulfated GAGs and its contribution to cell surface binding. Using GAG-deficient cells and competition experiments with soluble GAGs, we observed by confocal microscopy and flow cytometry that GAGs mediate the sequestration of secretin at the cell surface. Isothermal titration calorimetry and surface plasmon resonance revealed that secretin binds to heparin with dissociation constants ranging between 0.9 and 4 μM. By designing secretin derivatives with a restricted conformational ensemble, we observed that this interaction is mediated by the presence of a specific conformational GAG-recognition motif that decorates the surface of the peptide upon helical folding. The present study identifies secretin as a novel GAG-binding polypeptide and opens new research direction on the functional role of GAGs in the biology of secretin.


[Aerobic training guidelines in beta blocker therapy. An update].
Beta adrenergic blockers are first choice drugs in patients treated for hypertension, coronary heart disease, and patients recovering from myocardial infarction. In addition, aerobic exercise per se has proven to cause beneficial effects on those health problems. However, beta adrenergic blockade significantly effects aerobic hemodynamics and metabolism. These tremendous changes have to be taken under consideration when prescribing aerobic exercise for therapeutic purposes. In general, the guidelines for exercise prescription used for patients taking beta adrenergic blockers are similar to those used for healthy individuals. The factor that is most discussed is how to calculate the exercise intensity. The monitoring of exercise intensity with heart rate is acceptable for use as long as exercise intensity is determined while patient is on similar doses of beta adrenergic blocker at the time of exercise testing. RPE (rate perceived exertion) as an adjunct to heart rate in monitoring exercise intensity should be used. Chronic beta adrenergic blocker therapy with exercise training will improve aerobic capacity (VO2max) in healthy and hypertensive individuals, but the magnitude of improvement of VO2max is attenuated (approximately 10%) if compared to patients, suffering from coronary heart disease or recovering from myocardial infarction (+30%). Chronic beta adrenergic blocker therapy with aerobic exercise does not result in the lipid profile being improved. However, exercise training may be responsible for attenuating the beta adrenergic blocker induced deterioration of lipid profile normally seen. Although small, there seems to be an advantage to selective beta adrenergic blocker therapy, when combined with exercise training.


DIFFERENTIATION OF THE CHLOROPLAST OF ANTHOCEROS.
It has been demonstrated that the following changes accompany differentiation in the plastid of the liverwort Anthoceros eckloni. The inner membrane of the plastid folds to give rise to small vesicles which grow and may fuse to form thylakoids, i.e. flat bags. The thylakoids may "pair" to produce the doublets (thick membranes) of the grana. The doublets may be produced also by the invagination of a thylakoid. In both cases, the doublets are produced only where outside-to-outside contact of thylakoid membranes occurs, which supports the thesis that the thylakoid membranes are polarized. The thylakoids also fold outwards, anastomose, and may fuse. This results in a complicated membrane system, for which an interpretation becomes very difficult. The starch is produced in the matrix, and the pyrenoid bodies are interpreted as specialized regions of the matrix. Younger plastids have grana, but the mature plastid has so many doublets that distinct grana cannot be recognized. This interpretation of the changes which occur during the differentiation of the plastid differs radically from those of Menke (1961) and Manton (1962) who studied this same genus, but is compatible with findings in algae and angiosperms.


Pediatric anaphylaxis and hyper IgE syndrome.
Patients with autosomal-dominant (AD) hyper immunoglobulin E (IgE) syndrome (HIES) or Job syndrome develop frequent dermatologic and pulmonary infections. As patients have an extreme elevation of IgE levels, this database analysis study sought to study the association between AD HIES, Job syndrome, and anaphylaxis. HIES is a heterogeneous group of immune disorders characterized by extremely elevated levels of serum IgE. Although the molecular defects and clinical phenotypes found in association with Job syndrome are well characterized, the association with severe allergic reactions and anaphylaxis is a subject of ongoing investigation.


Effect of anodic metabolic function on bioelectricity generation and substrate degradation in single chambered microbial fuel cell.
Influence of anodic metabolic function viz., aerobic, anoxic and anaerobic on bioelectricity generation was evaluated in single chamber mediatorless microbial fuel cells (non-catalyzed graphite electrodes; open-air cathode) during wastewater treatment under similar operating conditions (pH 7; ambient temperature/pressure). Despite the fluctuations observed, aerobic metabolic function (379 mV; 538 mA/m2) documented higher power generation compared to anoxic (251 mV; 348 mA/m2) and anaerobic (265 mV; 211 mA/m2) operations. Relatively higher treatment efficiency was also evidenced in aerobic operation (COD removal efficiency; 77.68% (aerobic), 56.84% (anoxic), 48.68% (anaerobic)). Polarization behavior, bioelectrochemical analysis, sustainable resistance and cell potentials also supported the aerobic operation. Aerobic metabolic function showed potential to generate higher power and substrate degradation over the corresponding anoxic and anaerobic metabolic functions. The relative efficiency of power generation observed in aerobic microenvironment might be attributed to effective substrate oxidation and good biofilm growth observed on the anodic surface. Presence of lower dissolved oxygen concentration in anodic chamber due to the establishment of equilibrium between substrate oxidation and oxygen scavenging might also contributes positively to power generation in aerobic operation.


Vertebral Angiosarcoma. Case Study.
Bone angiosarcomas, especially vertebral angiosarcomas, are very rare. There are no studies based on large clinical samples in the literature, and only a few single case reports can be found. The symptoms of the disease are not specific. It is usually detected incidentally or at a late stage when pathological vertebral fractures or neurological complications occur. Diagnostic imaging and history help to recognize the tumour behind the symptoms, but do not allow accurate clinical diagnosis. The basis for a diagnosis is the histopathological examination supported by immunohistochemistry (IHC) assays. The case of a 26-year-old woman with an angiosarcoma involving the eighth thoracic vertebra we report reflects diagnostic problems adversely affecting the efficacy and accuracy of treatment offered to patients. The patient underwent three surgeries of the spine, including two biopsies. A needle biopsy did not provide sufficient information for the diagnosis. An open excisional biopsy, which at the same time temporarily reduced neurological deficits in the patient, was the only chance to obtain an accurate diagnosis. The third surgery was posterior decompression of the spinal cord due to the rapidly escalating paraparesis. It was not until 8 weeks later that the final diagnosis was established. At that time, the patient could not be qualified for any supplementary treatment. The patient died in hospital 6 months after the onset of disease.


Amnioinfusion for women with a singleton breech presentation and a previous failed external cephalic version: a randomized controlled trial.
Our trial aimed to assess the effectiveness of amnioinfusion for a second attempt at external cephalic version (ECV). This open randomized controlled trial was planned with a sequential design. Women at a term ≥36 weeks of gestation with a singleton fetus in breech presentation and a first unsuccessful ECV were recruited in two level-3 maternity units. They were randomly allocated to transabdominal amnioinfusion with a 500-mL saline solution under ultrasound surveillance or no amnioinfusion before the second ECV attempt. Trained senior obstetricians performed all procedures. The primary outcome was the cephalic presentation rate at delivery. Analyses were conducted according to intention to treat (NCT00465712). Recruitment difficulties led to stopping the trial after a 57-month period, 119 women were randomized: 59 allocated to amnioinfusion + ECV and 60 to ECV only. Data were analyzed without applying the sequential feature of the design. The rate of cephalic presentation at delivery did not differ significantly according to whether the second version attempt was or was not preceded by amnioinfusion (20 versus 12%, p = .20). Premature rupture of the membranes occurred for 15% of the women in the amnioinfusion group. Amnioinfusion before a second attempt to external version does not significantly increase the rate of cephalic presentation at delivery.


Model-independent steady-state plasma level predictions in autonomic nonlinear pharmacokinetics I: Derivation and theoretical analysis.
Current drug level predictions in nonlinear pharmacokinetics are based on specific pharmacokinetic models in contrast to the model-independent (structureless), dose-linearity, and superposition principles used in linear pharmacokinetics. Such model-dependent methods may not provide reliable predictions due to their inherent nonuniqueness, computational complexity, and often unrealistic kinetic assumptions. Some novel model-independent methods for predicting the steady-state drug levels of extravascular, intravenous bolus, and intravenous infusion administrations are presented that should overcome such disadvantages. The methods only assume an autonomic nonlinear kinetic behavior, which implies that following an intravenous bolus administration the derivatives of the drug concentration-time profile at arbitrary drug levels are independent of the dose given. Such a kinetic behavior is found for any nonlinear pharmacokinetic system when the rate of change of the drug level following an intravenous bolus administrations depends only on the drug level, i.e., dC/dt = -q(C), where q can be any function dependent only on C and time-invariant kinetic parameters. The basic approach presented represents a novel alternative which avoids the very difficult and often impractical task of identifying and incorporating the numerous kinetic parameters and processes responsible for the observed drug concentration data into a useful pharmacokinetic model. The focus in the kinetic analysis is instead on two much simpler processes: (a) fitting empirical functions to estimate the mean drug disposition behavior of the subject or population and (b) testing the validity of the assumptions involved.


[Fertility preservation and cancer in the male].
Improvement in cancer treatments resulted in an increased number of men surviving cancer. Quality of life has become an important issue in these patients. Anti cancer treatments might have transient or definitive harmful effects on male fertility. Sperm cryoconservation is currently the only proven method to preserve fertility in patients undergoing oncologic treatment. It should be proposed to every patient at reproductive age before chemotherapy, radiotherapy or any surgery involving reproductive tract. Despite low use rate, this simple method could allow patients presenting infertility after treatment to father a child.


Patterning of chick brain vesicles as revealed by peanut agglutinin and cholinesterases.
Differentiation of individual rhombomeres of the chicken hindbrain directly follows the emergence of primary brain vesicles. Immediately after the constriction of the prosencephalon at HH9, a series of vesicles of decreasing size is established almost simultaneously between HH9 and HH10, including mesencephalon, four preotic (R2-R5) and one postotic (R6/R7) rhombomeres. Thereby, the cranial neural tube is ventrally embedded in a mesodermal PNA-binding matrix that particularly accumulates underneath vesicular constriction sites, as demonstrated for the segregation of the prosencephalon at HH9 and the cerebellar rhombomere R1 from R2 at HH13. The subsequent period of hindbrain differentiation is analyzed by cholinesterase (AChE, BChE) and peanut lectin histochemistry, by the BrdU and the neurite-specific G4 antibodies. Preotically, differentiation of two pairs of rhombomeres (R4 + R5, R2 + R3) starts in R4, immediately followed by R2. The caudal rhombomeres of both pairs are delayed (R5, R3). Then the postotic rhombomere is subdivided, whereby R7 differentiates before R6. Thus, the development in the direct vicinity of the otic vesicle is delayed (R5, R6). R7 is the last rhombomere that is demarcated caudally. Based on these findings, we postulate two processes that may regulate rhombomere formation in the chicken embryo: (a) an early rostrocaudal wave establishing the major brain vesicles, (b) a superimposed pairwise segmentation emanating rostrally and caudally from the otic vesicle. The segregation of the cerebellar rhombomere is a late step.


[Brazilian Protocol for Sexually Transmitted Infections 2020: HIV infection in adolescents and adults].
HIV infection is the subject of one of the chapters of the "Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections", published by the Brazilian Ministry of Health in 2020. It is important that health professionals and managers learn the signs and symptoms of HIV infection and know how to diagnose it, in order to provide appropriate treatment and reduce complications. HIV infection has become a chronic disease and its treatment includes addressing common comorbidities in clinical practice such as arterial hypertension, diabetes and dyslipidemia, in addition to cardiac risk assessment, cancer prevention and guidance on immunization. Initiation of treatment for all HIV patients, regardless of clinical or immunological criteria, adopted by the Ministry of Health since 2013, has now been simplified with more tolerable first-line medications and with fewer drug interactions, which makes its management easy to implement, including by Primary Health Care.


Volumetric analysis of colonic distention according to patient position at CT colonography: diagnostic value of the right lateral decubitus series.
The purpose of this study was to compare total colonic gas volume and segmental luminal distention according to patient position on CT colonography (CTC), as well as to determine which two views should constitute the routine protocol. Volumetric analysis was retrospectively performed on CTC examinations from 146 adults (mean age, 59.2 years; 81 men and 65 women; mean body mass index [BMI], 30.9) for whom supine, prone, and right lateral decubitus series were sequentially obtained using continuous low-pressure CO2 insufflation. Total colonic gas volumes were assessed using a novel automated volumetric tool. In addition, two radiologists scored distention by segment using a 4-point scale (4=optimal; 3=adequate; 2=inadequate; 1=collapsed). Mean (±SD) colonic gas volumes for supine, prone, and decubitus positioning were 1617±567, 1441±505, and 1901±627, respectively (p<0.001). Colonic volume was highest on the right lateral decubitus series in 73.3% (107/146) and lowest in 6.2% (9/146) of cases, whereas the prone series was highest in 0.7% (1/146) and lowest in 73.3% (107/146) of cases. Overall mean segmental reader scores and percentages of inadequate or collapsed for supine, prone, and decubitus positions were 3.48, 3.33, and 3.71 and 10.4%, 12.1%, and 4.2%, respectively (p<0.001). The only mean segmental scores below 3.0 were the sigmoid colon on supine (2.68) and prone (2.58) series, compared with 3.23 on decubitus series (p<0.001). Improvement in distention in both decubitus and supine positions over the prone position increased further with increasing BMI (p<0.001). The right lateral decubitus position consistently yields the best colonic distention at CTC and significantly improves evaluation of the sigmoid colon. Prone distention was the worst, particularly as BMI increased. Routine supine and decubitus positioning should be considered for standard CTC protocols, particularly in obese individuals. Automated volumetric analysis provides for rapid objective assessment of colonic distention.


Unusual swelling of elastin.
The swelling behavior of the elastin network has been investigated by comparing the linear expansion of samples of purified elastin with the volume expansion of the network, calculated on the basis of composition. Elastin sample dimensions and sample masses were measured under three conditions in which volume changes: thermal expansion at fixed water contents, deswelling due to dehydration, and swelling to greater than normal levels due to the swelling agent, sodium dodecyl sulfate. Isotropic network swelling usually changes length in proportion to the cube root of network volume, but length was found to be directly proportional to volume, showing a greater increase in length than expected. This unusual swelling behavior is attributed to an unusual elastin structure at the subfiber level, but there is insufficient detail on elastin's molecular organization to identify a mechanism to explain how it occurs. Assuming the network swells homogeneously, we describe two models that correctly predict swelling behavior, but these models imply a significant deviation from the structure generally assumed for an elastomeric polymer network of kinetically free molecular chains. Assuming that the network swells heterogeneously removes part of the difficulty with the models, but the observed direct proportionality between length and network volume remains to be explained.


Development of a tool to measure the number of foods and beverages consumed by children using National Health and Nutrition Examination Survey (NHANES) FFQ data.
There is currently no standard, objective definition of selective eating. This is partially because normative values for the number of different foods eaten by US children have not been established. The present study objectives were to: (i) perform exploratory analysis on the number of different foods, beverages, and total foods and beverages consumed by US children aged 2-18 years over a year's time, and the types of foods consumed by those in the lowest 2·5th percentile; and (ii) determine whether those values differ according to demographic variables and weight status. Secondary analysis of cross-sectional FFQ data. Differences in number of foods, beverages, and total foods and beverages were analysed using one-way ANOVA. National Health and Nutrition Examination Survey (NHANES) for the years 2003-2006. Non-institutionalized US children aged 2-18 years. The mean number of different foods and beverages consumed across the sample was 83·2. There were no significant differences by gender, BMI, race or food security categories. There was a difference in beverage consumption by age category, with children aged 12-18 years consuming a significantly higher number of different beverages compared with each of the other two age categories (i.e. 2-5 years and 6-11 years). Normative values for the number of foods and drinks reported as consumed by children over the past 12 months may be a useful measure for researchers. Future research validating this measure is needed before cut-off values can be used to develop a definition of selective eating.


Successful management of sternomanubrial joint septic arthritis with pectoralis muscle flap closure: a case series.
Primary infection of the sternomanubrial joint (SMJ) is extremely rare. We present four consecutive cases who were all treated with SMJ resection (partial sternectomy), bilateral partial 2nd rib resection and immediate placement of temporary wound vacuum therapy followed by pectoralis major muscle flap closure. Average patient age was 35.5 years with male predominance (75%). All patients had intravenous drug use as underlying risk factor along with concomitant viral infections Hep C (75%) and HIV (25%). MSSA was identified in resection cultures in 75% of the patients. Delayed bilateral PMFC was achieved in all patients (average post-resection day 5). Response to treatment was excellent with no recurrent infections, no complications and zero 30-day mortalities. Our experience represents the largest reported case series in adults and would suggest that aggressive surgical resection followed by PMFC would appear to be the preferred treatment for all patients with SMJ infection.


'Learning to live your life again': An interpretative phenomenological analysis of weblogs documenting the inside experience of recovering from anorexia nervosa.
This study aimed to explore the construct of recovery from anorexia nervosa through the medium of weblogs, focusing on the benefits and barriers to the recovery process. Data were extracted from female ( n = 7) and male ( n = 1) participants' textual pro-recovery weblogs, all of which were posted between 2013 and 2015 in the public domain. Data were analysed using interpretative phenomenological analysis. Three superordinate themes were identified: (1) barriers to recovery, (2) factors increasing the likelihood of recovery and (3) support. Results suggest supportive relationships, regaining control and recognising the consequences of the eating disorder benefit recovery, whereas public perceptions, the anorexia nervosa voice and time act as barriers to recovery. Out of eight participants, four described seeking professional help as part of their recovery, of which three believed their professional therapy experience helped aid recovery. Implications for anorexia nervosa treatment are discussed in detail.


Hepatic phosphatidylethanolamine methyltransferase activity is decreased by ethanol and increased by phosphatidylcholine.
Phosphatidylethanolamine N-methyltransferase participates in the synthesis of membrane phosphatidylcholine. Its activity was reported to be decreased in patients with alcoholic cirrhosis, but it is not known whether this is a consequence of the cirrhosis or precedes it. This question was studied in a baboon model of alcohol-induced fibrosis. Phosphatidylethanolamine N-methyltransferase activity was measured in sequential percutaneous needle liver biopsies by the conversion of phosphatidylethanolamine to phosphatidylcholine, using radioactive S-adenosylmethionine as a methyl donor. Chronic alcohol consumption (1-6 years) significantly decreased hepatic phospholipid and phosphatidylcholine levels and reduced phosphatidyl-ethanolamine N-methyltransferase activity even before the development of fibrosis. These effects were prevented or attenuated by supplementing the diet with 2.8 g/1000 kcal of a preparation rich in dilinoleoyl phosphatidylcholine, a highly bioavailable phosphatidylcholine species. There were significant (p < 0.001) correlations between phosphatidylethanolamine N-methyltransferase activity and both hepatic phosphatidylcholine (r = 0.678) and total phospholipid (r = 0.662). 1. Alcohol consumption diminishes phosphatidylethanolamine N-methyltransferase activity prior to the development of cirrhosis and decreases the hepatic content of its product, namely phosphatidylcholine, a key component of cell membranes. This may promote hepatic injury and possibly trigger fibrosis. 2. Phosphatidylcholine administration ameliorates the ethanol-induced decrease in phosphatidylethanolamine N-methyltransferase activity and corrects phospholipid and phosphatidylcholine depletions, thereby possibly contributing to the protection against alcoholic liver injury.


Immunohistochemical study of the striatal efferents and nigral dopaminergic neurons in parkinsonism-dementia complex on Guam in comparison with those in Parkinson's and Alzheimer's diseases.
A comparative topographical immunohistochemical analysis was performed on the basal ganglia (including the substantia nigra) in Guamanian parkinsonism-dementia complex, idiopathic Parkinson's disease (PD), and Alzheimer's disease (AD). The striatal projection neurons and their efferent fibers were examined by using antibodies to calcineurin, methionine-enkephalin, and substance P. Tyrosine hydroxylase served as a marker for nigrostriatal dopaminergic neurons. The basal ganglia of patients with parkinsonism-dementia complex reacted strongly with all of the antibodies and the reaction products exhibited a normal distribution pattern. These findings suggest that the striatal output system is well preserved in patients with this disease. Similar results were obtained in patients with AD or PD. However, as compared to the patients with AD or PD, patients with parkinsonism-dementia complex showed severe reduction (greater than 90%) in the number of dopaminergic neurons in both the lateral and the medial portions of the substantia nigra. In view of the functional cortico-subcortical loops, these findings could explain the parkinsonian features and in part the cognitive impairment that occur in parkinsonism-dementia complex on Guam.


An in-depth look into the association between morningness-eveningness and well-being: evidence for mediating and moderating effects of personality.
Morningness-eveningness and standard personality traits are associated with well-being but few studies have directly compared the two types of construct as correlates of life satisfaction. Influences on well-being common to both chronotype and personality may include shared biological bases for depression and sleep disturbance, tendencies toward social jetlag, and emotion-regulation mechanisms. The current study tested mediation and moderation hypotheses in a sample of 379 Polish adults. The first hypothesis was that conscientiousness and emotional stability traits would mediate the relationship between morningness and life satisfaction. Consistent with previous results, morningness, the two personality traits, and satisfaction tended to be mutually positively correlated. A multiple mediation analysis showed that both traits partially mediated the morningness-satisfaction association. Data are compatible with morningness influencing personality development adaptively, although other causal hypotheses could be advanced. The second hypothesis was that extraversion would moderate the association between chronotype and satisfaction. This hypothesis was supported, with extraverted evening types showing disproportionately high life satisfaction, whereas introverted evening types showed the lowest levels of satisfaction. Level of extraversion may influence whether or not evening types choose to engage in adaptive social activities that boost well-being during the evening hours. Results demonstrate the importance of investigating both chronotype and personality in studies of well-being.


Developmental steps for radionuclide hysterosalpingography.
The active oviductal transportation capacity was studied in 73 infertile women by the use of a new deposition technique of radioactive particles into the internal cervical os. The main reason for this study was that a previous observation had shown that such a transportation capacity was lacking in 41% of the infertile patients with a normal hysterosalpingogram. The examination was performed in the immediate preovulatory phase, i.e. on days -3 to 0 before the ovulation, as measured by the basal body temperature during two preceding cycles. The deposition of 99mTc-labelled albumin particles of 0.2-1.0 micron at the internal cervical os and the interpretation of the radionuclide images are described in detail. The results show that the bilateral active tubal transportation capacity was present in 42 patients. An impaired transportation capacity was diagnosed in 22 patients. In 9 patients, the particles never reached the uterine cavity, or all activity leaked back to the vagina.


Anterior Fusion and Long-Term Cervical Mobility in Patients With Traumatic Spinal Cord Injury: An Observational Study.
Objective This study aims to determine and quantify the impairment of cervical mobility and range of motion in patients with traumatic spinal cord injury (SCI) and subsequent cervical subaxial fusion surgery. Methods A total of 89 patients who underwent interbody fusion of the cervical spine and were admitted to the Spinal Cord Injury Center of the BG Klinikum Hamburg, Germany between 2003 and 2018 were examined after their in-facility rehabilitation was successfully completed. Reclination, inclination, tilt, and rotation of the cervical spine were examined and documented in addition to overall patient characteristics and fusion extent. Results We could identify fusion length and age to be independently negatively correlated with the cervical range of motion in different degrees of movement. We could also show a significant decrease in cervical mobility within our patients when compared to healthy adults. The ability to tilt and rotate the cervical spine was particularly impaired. Conclusions Patients with traumatic SCI and intervertebral fusion suffer from significant impairment of mobility in different degrees of movement. This knowledge can be used to evaluate the rehabilitative challenges and reintegrative needs of individuals after traumatic SCI. Rehabilitation should be adjusted accordingly.


Bridging the macroscopic and atomistic descriptions of the electrocaloric effect.
First-principles-based simulations are used to simulate the electrocaloric effect (ECE) in Ba(0.5)Sr(0.5)TiO(3) alloys. In analogy with experimental studies we simulate the effect directly and indirectly (via the use of Maxwell thermodynamics). Both direct and indirect simulations utilize the same atomistic framework that allows us to compare them in a systematic way and with an atomistic precision for the very first time. Such precise comparison allows us to provide a bridge between the atomistic and macroscopic descriptions of the ECE and identify the factors that may critically compromise or even destroy their equivalence. Our computational data reveal the intrinsic features of ECE in ferroelectrics with multiple ferroelectric transitions and confirm the potential of these materials to exhibit giant electrocaloric response. The coexistence of negative and positive ECE in one material as well as an unusual field-driven transition between them is predicted, explained at an atomistic level, and proposed as a potential way to enhance the electrocaloric efficiency.


Reparative Mineralized Tissue Characterization after Direct Pulp Capping with Calcium-Silicate-Based Cements.
Nowadays, the preservation of dental pulp vitality is an integral part of our daily therapies. The success of these treatments depends on the clinical situation as well as the biomaterials used. Mineral Trioxide aggregate and BiodentineTM are commonly used as pulp capping materials. One objective of vital pulp therapy is the repair/regeneration of the pulp. In addition to the initial inflammatory status of the pulp, the nature and quality of the new mineralized tissue obtained after pulp capping directly influence the success of the treatment. In order to characterize the reparative dentin, in the current study, the chemical composition and microstructure of the dentin bridge after direct pulp capping using Biodentine™ and mineral trioxide aggregate (MTA) was studied by using Raman microspectroscopy and scanning electron microscopy, respectively. The results showed that the reparative dentin bridge observed in both groups presented dentin tubules and chemical composition similar to primary dentin. With the limitations of this study, the calcium-silicate-based cements used as pulp capping materials provide an optimal environment for pulp healing, resulting in a reparative dentin resembling on certain points of the primary dentin and the regeneration of the pulp.


Limitations on geminivirus genome size imposed by plasmodesmata and virus-encoded movement protein: insights into DNA trafficking.
Animals and plants evolved systems to permit non-cell-autonomous trafficking of RNA, whereas DNA plays a cell-autonomous role. In plants, plasmodesmata serve as the conduit for this phenomenon, and viruses have evolved to use this pathway for the spread of infectious nucleic acids. In this study, a plant DNA virus was used to explore the constraints imposed on the movement of DNA through this endogenous RNA trafficking pathway. The combined properties of the geminivirus-encoded movement protein and plasmodesmata were shown to impose a strict limitation on the size of the viral genome at the level of cell-to-cell movement. Size-increased viral genome components underwent homologous and nonhomologous recombination to overcome this strict limitation. Our results provide insights into the genetic mechanisms that underlie viral evolution and provide a likely explanation for why relatively few types of plant DNA viruses have evolved: they would have had to overcome the constraints imposed by an endogenous system operating to ensure that DNA acts in a cell-autonomous manner.


Reversal of the inhibition of photosynthesis by herbicides affecting hydroxyphenylpyruvate dioxygenase by plastoquinone and tocopheryl derivatives in Chlamydomonas reinhardtii.
Isoxaflutole or pyrazolate inhibition of tocopherol and plastoquinone biosynthesis in the green alga Chlamydomonas reinhardtii Dang leads to the inactivation of photosystem II and the degradation of its reaction centre D1 protein when exposed to strong light. Cell-permeable short-chain derivatives of plastoquinone and tocopherol were tested in the reversal. Addition of decyl-plastoquinone reverses herbicide-induced inhibition of photosynthesis and inactivation of photosystem II in short-time (1 h) exposure of the algae to high light. In high light longer than 1 h, decyl-plastoquinone alone loses effectiveness, but a synthetic permeable tocopheryl derivative retards the inhibitory effects on photosystem II and on the degradation of the D1 protein. This indicates that tocopherol deficiency induced by the herbicides makes a major contribution to their secondary mode of action in high light stress.


Using a Thermal Imaging Camera to Locate Perforators on the Lower Limb.
Reconstruction of the lower limb presents a complex problem after skin cancer surgery, as proximity of skin and bone present vascular and technical challenges. Studies on vascular anatomy have confirmed that the vascular plane on the lower limb lies deep to the deep fascia. Yet, many flaps are routinely raised superficial to this plane and therefore flap failure rates in the lower limb are high. Fascio-cutaneous flaps based on perforators offer a better cosmetic alternative to skin grafts. In this paper, we detail use of a thermal imaging camera to identify perforator 'compartments' that can help in designing such flaps.


[Effectiveness of three whitening dentifrices].
Over the past years the market share of whitening dentifrices has been increasing. The aim of this parallel, randomized, double-blind clinical trial was to assess the efficiency of three commercially available tooth whitening dentifrices. Thirty-six subjects with extrinsic tooth stain (A3 and darker) were randomly assigned to three groups (A, B, C) of twelve subjects each. Group A brushed their teeth twice daily with Durodont medical fresh and white (RDA 70), Group B with Friscodent Zahnweiss (RDA 87) and Group C with a combination of Durodont Zahnweiss intensiv (RDA 166) and Durodont medical fresh and white. At baseline and after four and eight weeks the color of the anterior teeth was evaluated using a VITAPAN classical color shade and a special colorimeter (Homeba). The colors of the shade guide were arranged and nummerized by value. After four and eight weeks of use each dentifrice showed a significant whitening effect compared to baseline (p < or = 0.05). There were, however, no significant differences between the groups. Moreover both methods showed similar results. Thus, the results support a significant "whitening" effect of all three dentifrices.


THE LARVAE OF A DISCINID (INARTICULATA, BRACHIOPODA).
1. Thirty-three discinid larvae were obtained one meter below the water surface in the daytime in the shallow part of the Johore Strait, north of Singapore. 2. The oldest among them, 462 µ in longitudinal diameter, resembled the "Mueller's larva" discovered by Mueller and referred to Pelagodiscus atlanticus (King) by many subsequent authors. 3. The youngest among them, 108 µ long and 115 µ wide in dorsal shell, resembled Simroth's smaller discinid larva of 220 µ diameter in many essential features. 4. The larvae in this study showed a gradual transition in many morphological characters, indicating that they were a series of developmental stages in the ontogeny of a single discinid species. 5. The two bunches of long embryonic setae were gradually replaced by the curved early larval setae in the medium-sized specimens. Towards the close of the larval stage the third kind of setae appeared from the mantle border. 6. The dorsal shell valve maintained its oval shape during the entire larval stage. The posterior edge of the ventral one, however, gradually changed from convex to concave, passing through a stage when it was almost a straight line. 7. The statocysts and the pedicle appeared in older larvae. 8. The number of cirri remained constant throughout the larval stage. 9. The larvae were compared with the discinid larvae previously recorded. Their developmental changes and the breeding season of discinids were discussed.


Pain is the Greatest Preoperative Concern for Patients and Parents Before Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.
Prospective cross-sectional study. To evaluate patients' and parents' concerns so they can be addressed with appropriate preoperative counseling. Despite much research on outcomes for posterior spinal fusion (PSF) in adolescent idiopathic scoliosis (AIS), little is available about preoperative fears or concerns. Patients with AIS undergoing PSF, their parents, and surgeons were prospectively enrolled and asked to complete a survey on their fears and concerns about surgery at their preoperative appointment. Forty-eight patients and parents completed surveys. Four attending pediatric spine surgeons participated and submitted 48 responses. Mean age of patients was 14.2 years. On a scale of 0 to 10, mean level of concern reported by parents (6.9) was higher than that reported by patients (4.6). Surgeons rated the procedure's complexity on a scale of 0 to 10 and reported a mean of 5.2. Neither patients' nor parents' level of concern correlated with the surgeons' assessment of the procedure's complexity level (R = 0.19 and 0.12, P = 0.20 and P = 0.42, respectively). Top three concerns for patients were pain (25%), ability to return to activities (21%), and neurologic injury (17%). Top three concerns for parents were pain (35%), neurologic injury (21%), and amount of correction (17%). Top three concerns for surgeons were postoperative shoulder balance (44%), neurologic injury (27%), and lowest instrumented vertebrae selection (27%). Patients reported the same concerns 23% of the time as parents, and 17% of the time as surgeons. Parents and surgeons reported the same concerns 21% of the time. Pain was the greatest concern for both patients and parents but was rarely listed as a concern by surgeons. Parent and patient level of concern did not correlate to the surgeon's assessment of the procedure's complexity. Neurologic injury was a top concern for all groups, but otherwise there was little overlap between physician, patient, and parent concerns. 3.


Tools to assess psychological trauma & its correlates in child sexual abuse: A review & current needs in Asia.
Absence of visible physical symptoms and limited capacity to express trauma directly, pose significant challenges in assessment of its exact nature of trauma and its correlates in child sexual abuse. There are numerous assessment tools however, deciding upon the appropriateness is often challenging in Asian socio-cultural and health care set up. A review would provide a ready reference to the practioner regarding the exact clinically utility of the tools and also would guide them in the direction of culture specific modifications. Computerized databases namely Medline, PsycINFO, Health and Psychosocial Instruments, and Social Sciences Citation Index were used. 52 scales were obtained and analysed in terms of scale characteristics, reference to theory and DSM, and cultural competency. Despite of a wide variety of methods, and newer instruments, many of the traditionally used techniques of child's internal thinking and emotional assessment appear outdated while reviewing the recent theories of CSA related psychological trauma. An integrated format, incroporating child-parent-clinicain rating, with multiple domain speciafic items and verbal and non-verbal tasks, is the current need in the Asian region.


Rapalogs and mTOR inhibitors as anti-aging therapeutics.
Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has the strongest experimental support to date as a potential anti-aging therapeutic in mammals. Unlike many other compounds that have been claimed to influence longevity, rapamycin has been repeatedly tested in long-lived, genetically heterogeneous mice, in which it extends both mean and maximum life spans. However, the mechanism that accounts for these effects is far from clear, and a growing list of side effects make it doubtful that rapamycin would ultimately be beneficial in humans. This Review discusses the prospects for developing newer, safer anti-aging therapies based on analogs of rapamycin (termed rapalogs) or other approaches targeting mTOR signaling.


Regulating Chemokine-Receptor Interactions through the Site-Specific Bioorthogonal Conjugation of Photoresponsive DNA Strands.
Oligonucleotide conjugation has emerged as a versatile molecular tool for regulating protein activity. A state-of-the-art labeling strategy includes the site-specific conjugation of DNA, by employing bioorthogonal groups genetically incorporated in proteins through unnatural amino acids (UAAs). The incorporation of UAAs in chemokines has to date, however, remained underexplored, probably due to their sometimes poor stability following recombinant expression. In this work, we designed a fluorescent stromal-derived factor-1β (SDF-1β) chemokine fusion protein with a bioorthogonal functionality amenable for click reactions. Using amber stop codon suppression, p-azido-L-phenylalanine was site-specifically incorporated in the fluorescent N-terminal fusion partner, superfolder green fluorescent protein (sfGFP). Conjugation to single-stranded DNAs (ssDNA), modified with a photocleavable spacer and a reactive bicyclononyne moiety, was performed to create a DNA-caged species that blocked the receptor binding ability. This inhibition was completely reversible by means of photocleavage of the ssDNA strands. The results described herein provide a versatile new direction for spatiotemporally regulating chemokine-receptor interactions, which is promising for tissue engineering purposes.


Effects of pretreatments of banana (Musa AAA,Omini) on the composition, rheological properties, and baking quality of its flour and composite blends with wheat flour.
Effects of chemical and heat pretreatments on the protein, gluten, and alpha-amylase activity, pasting (Peak [P], Final [F] setback [S] viscosity, pasting temperature [PT] and time [T]) and alveogram (Energy [E], maximum inflation [MI], P/L, and elasticity index [EI]) properties of flour from the pretreated bananas and its composite with wheat flour (WF) were examined. The baking (water absorption [WA] and specific volume [SV]) and sensory properties of bread produced from the flour were also examined. Protein, gluten, and alpha-amylase activity ranged from 4.75 ± 0.07%, 30.25 ± 0.05%, and 4.00 ± 0.05 min to 13.75 ± 0.06%, 35.64 ± 0.06%, and 39.61 ± 1.18 min with WF:PTBF/95:05, WF:CTBF/00:100, WF:BBF/80:20, WF:100 and WF:CTBF/00:100, WF:PTBF/95:05, WF:100, WF:PTBF/00:100 having lowest and highest values, respectively. P, F, S viscosities, PT and T ranged from 186.17 ± 0.71, 217.08 ± 1.41, 38.92 ± 5.42 RVU, 84.70 ± 0.28°C, 5.04 ± 0.05 min to 461.0 ± 5.07, 348.5 ± 8.84, 88.83 ± 0.24 RVU, 87.20 ± 0.00°C, 6.24 ± 0.05 min, respectively. E, MI, P/L, and EI ranged from 141.50 ± 0.71 × 10-4J, 15.35 ± 0.07, 0.59 ± 0.83 and 35.85 ± 0.07 to 325.00 ± 1.4 × 10-4J, 22.55 ± 0.07, 2.75 ± 0.07, and 70.50 ± 0.71, respectively. WA and SV were 48.12 ± 0.07 to 52.60 ± 0.14 and 2.850 ± 0.07 to 5.635 ± 0.18 with the WF having significantly (P < 0.05) higher values than other blends and the most acceptable in terms of appearance and taste.


Rhinitis, sinusitis and the yellow nail syndrome: a review of symptoms and response to treatment in 17 patients.
A total of 17 patients with yellow nail syndrome are described. Their symptoms, age of onset and severity are examined with particular reference to the presence of rhinosinusitis. Fourteen of the patients (83%) suffered severe rhinosinusitis, which pre-dated nail changes in four, coincided with yellow nails in six, and occurred later in the remaining patients. In general, patients responded poorly to conventional medical and surgical treatment, with the exception of functional endoscopic sinus surgery (FESS) which may be of value in these patients. The frequent association of rhinosinusitis with yellow nails may warrant its recognition as part of the syndrome. Careful inspection of the fingernails in all patients presenting with severe rhinosinusitis is warranted.


Early Subclinical Atherosclerosis in Gestational Diabetes: The Predictive Role of Routine Biomarkers and Nutrigenetic Variants.
Gestational diabetes mellitus (GDM) can be considered a silent risk for out-of-pregnancy diabetes mellitus (DM) and cardiovascular disease (CVD) later in life. We aimed to assess the predictive role of 3rd trimester lipid profile during pregnancy for the susceptibility to markers of subclinical atherosclerosis (CVD susceptibility) at 3 years in a cohort of women with history of GDM. A secondary aim is to evaluate the usefulness of novel nutrigenetic markers, in addition to traditional parameters, for predicting early subclinical atherosclerosis in such women in order to plan adequate early prevention interventions. We assessed 28 consecutive GDM women in whom we collected socio-demographic characteristics and clinical and anthropometric parameters at the 3rd trimester of pregnancy. In a single blood sample, from each patient, we assessed 9 single nucleotide polymorphisms (SNPs) from 9 genes related to nutrients and metabolism, which were genotyped by High Resolution Melting analysis. All women then attended a 3-year-postpartum follow-up and on that occasion performed an oral glucose tolerance test (OGTT, with 75 g oral glucose), the measurement of carotid artery intima-media thickness (cIMT), and analyses of metabolic parameters. In addition, we evaluated the physical activity level and the adherence to Mediterranean diet (MedDiet) using the International Physical Activity Questionnaire (IPAQ-short version) and PREDIMED questionnaires. We found an association between 3rd trimester triglycerides and cIMT (p = 0.014). We also found significant associations between the APOA5 CC genotype and cIMT after adjustments for age and body mass index (p = 0.045) and between the interaction CC APOA5/CC LDLR and cIMT (p = 0.010). At the follow-up, the cohort also featured a mean BMI in the overweight range and a high mean waist circumference. We found no difference in the MedDiet adherence, physical activity, and smoking but an inverse correlation between the PREDIMED and the IPAQ scores with the IMT. In conclusion, this preliminary study provides insight into the predictive role of lipid profile during pregnancy and of some genetic variants on cIMT taken as a parameter of subclinical CVD susceptibility in GDM.


Revisiting the Relationship Between Correlation Coefficient, Confidence Level, and Sample Size.
In the field of computational chemistry, it is a very common task to compare the predictive power of theoretical models with Pearson correlation coefficients. A general understanding is that larger sample sizes lead to increased precision. However, what is the minimum sample size required for comparing two models? This issue has not been well addressed in this field. To the best of our knowledge, the only serious study of this kind was published by Carlson in 2013 [ J. Chem. Inf. Model. 2013 , 53 1837 - 1841 ], where they proposed a method for estimating the minimum sample size required by this task. Considering how a benchmark comparison is conducted in reality, we want to point out that (i) the possible intercorrelation between two models should not be neglected and (ii) the one-sided test is more reasonable because comparison direction is known a priori. Carlson's method has significantly overestimated the required minimum sample size due to these two issues. Here, we will describe a more appropriate method based on Dunn and Clark's test statistic, and we have designed an extensive numerical test to validate our method. The minimum sample sizes required by comparing two models under various conditions are computed with our method. Our study has shown that the required minimum sample size is determined by several factors, including confidence, power, correlation coefficients as well as the intercorrelation between two models. As a rule of thumb, a couple of hundred samples are sufficient at 90% confidence or above for comparing two models producing meaningful R values.


The pulsating orb: solving the wave equation outside a ball.
Transient acoustic waves are generated by the oscillations of an object or are scattered by the object. This leads to initial-boundary value problems (IBVPs) for the wave equation. Basic properties of this equation are reviewed, with emphasis on characteristics, wavefronts and compatibility conditions. IBVPs are formulated and their properties reviewed, with emphasis on weak solutions and the constraints imposed by the underlying continuum mechanics. The use of the Laplace transform to treat the IBVPs is also reviewed, with emphasis on situations where the solution is discontinuous across wavefronts. All these notions are made explicit by solving simple IBVPs for a sphere in some detail.


Use of metformin and survival of patients with high-grade glioma.
High-grade glioma (HGG) is associated with poor prognosis. Drug repurposing evolves as new modality to improve standard therapy. The antidiabetic drug metformin has been found to inhibit glioma cell growth in vitro and in vivo. The aim of the present retrospective cohort study was to evaluate the survival of patients with HGG with or without treatment with metformin, based on a large cohort of a cancer registry. The analysis included 1,093 patients with HGG diagnosed between 1998 and 2013 from the population-based clinical cancer registry Regensburg (Germany), which covers 2.1 Mio inhabitants and 98% of all cancer diagnoses. We performed multivariable adjusted Cox-regression analyses. Hazard Ratios (HRs) with 95% Confidence Intervals (CIs) for overall survival (OS) and progression-free survival (PFS) of patients with HGG with or without treatment with metformin were obtained. Use of metformin was associated with a significantly better overall and progression-free survival of patients with WHO grade III glioma (HR for OS = 0.30; 95% CI = 0.11-0.81, HR for PFS = 0.29; 95% CI = 0.11-0.78), while there were no significant relations with OS (HR = 0.83; 95% CI = 0.57-1.20) or PFS (HR = 0.85; 95% CI = 0.59-1.22) in patients with WHO grade IV glioma. In conclusion, use of metformin is associated with better overall and progression-free survival of patients with WHO grade III. Possible underlying mechanisms include the higher prevalence of IDH mutations in WHO grade III glioma, which might sensitize to the metabolic drug metformin.


Green synthesis of highly stable carbon nanodots and their photocatalytic performance.
The present study reports a novel, facile, biosynthesis route for the synthesis of carbon nanodots (CDs) with an approximate quantum yield of 38.5%, using Musk melon extract as a naturally derived-precursor material. The synthesis of CDs was established by using ultraviolet-visible (UV-vis) spectroscopy, Dynamic light scattering, photoluminescence spectroscopy, X-ray diffraction, transmission electron microscopy and Fourier transform infrared (FTIR) spectroscopy. The as-prepared CDs possess an eminent fluorescence under UV-light (λex = 365 nm). The size range of CDs was found to be in the range of 5-10 nm. The authors further explored the use of such biosynthesised CDs as a photocatalyst material for removal of industrial dye. Degradation of methylene blue dye was performed in a photocatalytic reactor and monitored using UV-vis spectroscopy. The CDs show excellent dye degradation capability of 37.08% in 60 min and reaction rate of 0.0032 min-1. This study shows that synthesised CDs are highly stable in nature, and possess potential application in wastewater treatment.


Absorption and metabolism of xanthophylls.
Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.


Hormonal profiles in anovulatory patients treated with gonadotropins and synthetic luteinizing hormone releasing hormone.
Ten patients with hypothalamic anovulation weretreated with a "retard" preparation of synthetic luteinizing hormone releasing hormone (LHRH) after an HMG stimulation in order to induce ovulation and pregnancy. Four of the patient ovulated after intramuscular administration of the LHRH preparation. This study suggests that is is possible to induce ovulation with LHRH in patients pretreated with HMG, and that LHRH has advantages over HCG since it does not induce hyperstimulation even in the presence of exagerated follicular growth. Nevertheless, the optimal conditions for the use and monitoring of LHRH treatment have yet to be clarified.


The oral [(13)C]bicarbonate technique for measurement of short-term energy expenditure of sled dogs and their physiological response to diets with different fat:carbohydrate ratios.
The oral [(13)C]bicarbonate technique (o(13)CBT) was assessed for the determination of short-term energy expenditure (EE) under field conditions. A total of eight Alaskan huskies were fed two experimental diets in a cross-over experiment including two periods of 3 weeks. Effects of diets on EE, apparent total tract digestibility (ATTD) and on plasma hormones, blood lactate and glucose were furthermore investigated. The percentages of metabolisable energy derived from protein (P), fat (F) and carbohydrates (C) were 26:58:16 in the PFC diet and 24:75:1 in the PF diet. Measurements of EE were performed in the post-absorptive state during rest. Blood samples were collected during rest and exercise and ATTD was determined after days with rest and with exercise. EE was higher (P < 0·01) in period 2 than in period 1 (68 v. 48 kJ/kg body weight(0·75) per h). The ATTD of organic matter, crude protein and crude fat was higher (P < 0·01) in the PF diet compared with the PFC diet, and lower (P < 0·01) for total carbohydrates. Exercise did not affect ATTD. Higher (P < 0·01) insulin-like growth factor 1 and leptin concentrations were measured when fed the PF diet compared with the PFC diet. Concentrations of insulin decreased (P < 0·01), whereas cortisol and ghrelin increased (P < 0·05), after exercise. There was no effect of diet on blood lactate and glucose, but higher (P < 0·001) lactate concentrations were measured in period 1 than in period 2. The results suggest that the o(13)CBT can be used in the field to estimate short-term EE in dogs during resting conditions. Higher ATTD and energy density of the PF diet may be beneficial when energy requirements are high.


Neoadjuvant treatment sequencing adds value to the care of patients with operable pancreatic cancer.
Treatment sequencing for resectable pancreatic cancer remains controversial and there is lack of level one evidence comparing neoadjuvant versus adjuvant strategies. However, a comparison of the cost-effectiveness analysis of the treatment strategies may help to better define the healthcare value of each approach. This review will highlight the rationale for multimodality therapy in the treatment of pancreatic cancer, discuss the advantages and disadvantages of adjuvant therapy, and conceptualize the cost-effectiveness of a neoadjuvant approach with regard to healthcare value. J. Surg. Oncol. 2016;114:291-295. © 2016 Wiley Periodicals, Inc.


K65R-associated virologic failure in HIV-infected patients receiving tenofovir-containing triple nucleoside/nucleotide reverse transcriptase inhibitor regimens.
High rates of early virologic failure associated with the emergence of the K65R mutation in HIV-1 reverse transcriptase (RT) have been reported among HIV-infected patients who received novel, tenofovir-containing, triple-nucleoside/nucleotide reverse transcriptase inhibitor (NRTI/NtRTI) regimens as their initial therapy. This review surveys the findings of prospective and retrospective studies in this regard, examines the significance of the K65R mutation and other factors associated with reports of early virologic failure among patients receiving tenofovir-containing NRTI/NtRTI regimens, and discusses clinical approaches to preventing and managing HIV drug resistance and treatment failure associated with the K65R mutation.


Measurement of respiratory acoustic signals. Effect of microphone air cavity depth.
The use of electret microphones to measure lung sounds is widespread because of their small size, high fidelity, and low cost. Typically, an air cavity is placed between the skin surface and the microphone to convert the chest wall vibrations into a measurable sound pressure. The importance of air cavity depth on this transduction process was investigated in this study. An acoustic model of chest wall--air cavity--microphone interface was developed and the predicted effects of depth were compared with measurements performed using an artificial chest wall and lung sounds from a healthy subject. Model predictions are in general agreement with both in vitro and in situ measurements and indicate that the overall high-frequency response of the transduction diminishes with increasing cavity depth. This finding suggests that smaller cavity depths are more appropriate for detection of lung sounds over a wide band width and stresses the importance of coupler size on microphone measurements.


Hyperthermic intraperitoneal chemotherapy in locally advanced and recurrent ovarian carcinoma: surgical and oncological outcomes in the Indian public healthcare system.
This study analyzed the surgical outcomes after initial implementation of a cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) program in government settings in India. Methods: Ovarian cancer patients undergoing cytoreductive surgery and HIPEC from May 2015 to April 2019 were identified from a prospectively maintained database. Treatment characteristics and surgical outcomes were analyzed. Results: The study identified 101 patients. The mean peritoneal cancer index (PCI) was 7 ± 6, with higher PCI scores in primary and recurrent cases. Major morbidities were recorded in 24.7% of patients. High PCI score, completeness of cytoreduction and major morbidities were independent predictors of overall survival in multivariate analysis. Conclusion: The application of HIPEC in limited-resource settings is feasible with acceptable major morbidities. This program should receive similar priority in government systems.


Conically degenerate anchoring effect in planar nematic-liquid-crystal shells.
We study the defect texture in symmetric and asymmetric states of a nematic-liquid-crystal shell with conic and planar degenerate surface anchorings on the inner and outer spherical boundaries, respectively. To achieve the equilibrium nematic orientation, we numerically minimize the Landau-de Gennes free energy by employing surface potentials on the shell walls. The symmetric nematic shells energetically have stable configurations independent of thickness. In thick shells, the director field satisfies bipolar and hexadecapolar configurations between boundaries. In thin shells, the boojums transform into two stable disclination curves.


Methods of robustness analysis for Boolean models of gene control networks.
As a discrete approach to genetic regulatory networks, Boolean models provide an essential qualitative description of the structure of interactions among genes and proteins. Boolean models generally assume only two possible states (expressed or not expressed) for each gene or protein in the network, as well as a high level of synchronisation among the various regulatory processes. Two possible methods of adapting qualitative models to incorporate the continuous-time character of regulatory networks, are discussed and compared. The first method consists of introducing asynchronous updates in the Boolean model. In the second method, the approach introduced by Glass is adopted to obtain a set of piecewise linear differential equations that continuously describe the states of each gene or protein in the network. Both methods are applied to a Boolean model of the segment polarity gene network of Drosophila melanogaster. The dynamics of the model is analysed, and a theoretical characterisation of the model's gene pattern prediction is provided as a function of the timescales of the various processes.


Defects and Charge-Trapping Mechanisms of Double-Active-Layer In-Zn-O and Al-Sn-Zn-In-O Thin-Film Transistors.
Active matrix organic light-emitting diodes (AMOLEDs) are considered to be a core component of next-generation display technology, which can be used for wearable and flexible devices. Reliable thin-film transistors (TFTs) with high mobility are required to drive AMOLEDs. Recently, amorphous oxide TFTs, due to their high mobility, have been considered as excellent substitutes for driving AMOLEDs. However, the device instabilities of high-mobility oxide TFTs have remained a key issue to be used in production. In this paper, we present the charge-trapping and device instability mechanisms of high-mobility oxide TFTs with double active layers, using In-Zn-O (IZO) and Al-doped Sn-Zn-In-O (ATZIO) with various interfacial IZO thicknesses (0-6 nm). To this end, we employed microsecond fast current-voltage (I-V), single-pulsed I-V, transient current, and discharge current analysis. These alternating-current device characterization methodologies enable the extraction of various trap parameters and defect densities as well as the understanding of dynamic charge transport in double-active-layer TFTs. The results show that the number of defect sites decreases with an increase in the interfacial IZO thickness. From these results, we conclude that the interfacial IZO layer plays a crucial role in minimizing charge trapping in ATZIO TFTs.


Mutational Analysis of the GXXXG/A Motifs in the Human Na+/Taurocholate Co-Transporting Polypeptide NTCP on Its Bile Acid Transport Function and Hepatitis B/D Virus Receptor Function.
Homodimerization is essential for plasma membrane sorting of the liver bile acid transporter NTCP and its function as Hepatitis B/D Virus (HBV/HDV) receptor. However, the protein domains involved in NTCP dimerization are unknown. NTCP bears two potential GXXXG/A dimerization motifs in its transmembrane domains (TMDs) 2 and 7. The present study aimed to analyze the role of these GXXXG/A motifs for the sorting, function, and dimerization of NTCP. The NTCP mutants G60LXXXA64L (TMD2), G233LXXXG237L (TMD7) and a double mutant were generated and analyzed for their interaction with wild-type NTCP using a membrane-based yeast-two hybrid system (MYTH) and co-immunoprecipitation (co-IP). In the MYTH system, the TMD2 and TMD7 mutants showed significantly lower interaction with the wild-type NTCP. In transfected HEK293 cells, membrane expression and bile acid transport activity were slightly reduced for the TMD2 mutant but were completely abolished for the TMD7 and the TMD2/7 mutants, while co-IP experiments still showed intact protein-protein interactions. Susceptibility for in vitro HBV infection in transfected HepG2 cells was reduced to 50% for the TMD2 mutant, while the TMD7 mutant was not susceptible for HBV infection at all. We conclude that the GXXXG/A motifs in TMD2 and even more pronounced in TMD7 are important for proper folding and sorting of NTCP, and so indirectly affect glycosylation, homodimerization, and bile acid transport of NTCP, as well as its HBV/HDV receptor function.


Migration of lymphocytes sensitized against syngeneic and allogeneic spinal cord after infusion into susceptible and resistant syngeneic and semi-allogeneic hosts.
Lymphocytes from rats that had been sensitized against spinal cord were infused into unsensitized hosts, and the ability of cells subsequently recovered from the thoracic duct lymph of these recipients to mount anti-neural responses was tested. Lymph from normal recipients frequently contained reactive lymphocytes during the 4 days following infusion of sensitized cells, whereas cells that had been recovered from transfused rats, resistant to encephalomyelitis as a result of neonatal treatment, were almost invariably benefit of activity. If lymphocytes reactive against allogeneic neural cells were passaged through F1 hybrids of the lymphocyte and sensitizing allogeneic tissue strains, loss or retention of their ability to attack allogeneic neural cells was determined by the method of sensitization of the original lymphocyte donor.


Ultratrace analysis based on Hadamard transform capillary electrophoresis.
Hadamard transform capillary electrophoresis, which is based on a multiple sample injection technique, was combined with laser-induced fluorometry and utilized in the determination of analytes at subpicomolar levels. The sensitivity was substantially improved by increasing the order, i.e., the number of elements, of the Hadamard matrix. In fact, the signal-to-noise ratio was enhanced 18-fold by the use of a matrix of order 2047. A feasibility study was carried out by computer simulation to study the detection of an average of less than a single molecule in a single injection volume. The signal peak was clearly observable even under conditions at which only 0.3 molecule is present in the volume. Thus, this approach is potentially useful for ultratrace analysis, in which conventional single-injection capillary electrophoresis cannot be applied.


Use of intrathecal baclofen for treatment of severe spasticity in selected patients with motor neuron disease.
To assess the safety and efficacy of intrathecal baclofen (ITB) therapy for severe spasticity in patients with upper-motor neuron predominant motor neuron disease (U-MND). A total of 44 patients with U-MND were referred for discussion of ITB therapy. Baseline and outcomes data were extracted on 35 patients from a clinical spasticity registry at a tertiary referral center. Patients choosing to initiate ITB (n = 20) were compared with those choosing conservative therapy (n = 15). At baseline, lower average pain score in the non-ITB group was the only significant difference between the 2 groups. A significant reduction in pain scores, Modified Ashworth Scale (MAS), Spasm Frequency Scale, and requirement for oral spasticity medications was observed within the ITB group at early and late follow-up. Within the non-ITB group, there was a significant increase in MAS scores between baseline and late follow-up. A statistically significant difference favoring the ITB group was observed for change in MAS score (P < .0001), Numerical Rating Scale pain score (P = .04), dose of oral baclofen (P = .002) and tizanidine (P = .003), and number of oral medications for spasticity (P = .002). There was no difference between the 2 groups in the progression of hip flexor weakness or in the proportion of patients who became nonambulatory. Our findings suggest that ITB can effectively reduce spasticity and related symptoms without compromising function in selected patients with U-MND.


Goal-Directed Drinking Behaviors Can Be Modified Through Behavioral Mimicry.
This study tested whether behavioral mimicry can alter drinking behavior. It was hypothesized that participants would increase drinking behaviors given increased confederate drinking but not cup touching. Nineteen healthy adults (Mage = 20.32 years) completed 2 picture description tasks; during 1 task, a confederate frequently sipped water (complete drinking gesture), and during the other, the confederate touched her cup but did not drink (partial gesture). Outcome measures included number of drinks per minute, number of cup touches per minute, percentage of time spent drinking, and percentage of time spent touching the cup. Participants spent more time drinking and had an increased drinking rate during the drinking condition versus the cup-touching condition. For a majority of participants, drinking rate increased during the drinking condition versus baseline. Drinking, but not cup touching, rate also increased given increased confederate cup touching for many. Mimicry likely contributes to social modeling of drinking behaviors. This effect appears more robust given a complete target gesture (full drink); however, a partial goal-directed drinking gesture may also yield a mimicked response. Beyond the theoretical implications, these results provide directions for research investigating more naturalistic mechanisms for increasing dietary intake in various patient populations (e.g., individuals with dysphagia).


[Importance of laryngologic examination in chronic cough].
This study aims to investigate the distribution of etiologic factors related to otorhinolaryngology in chronic cough patients with normal lung examination and spirometric findings, and also highlight the importance of videolaryngostroboscopic (VLS) examination with these patients. Seventy-six patients (31 males, 45 females; mean age 48.0±15.5 years; range 18 to 83 year) who applied to pulmonology outpatient clinic with cough complaint for more than two months were included in the study. After being evaluated by a pulmonologist, patients were referred to otolaryngology outpatient clinic. To detect the underlying cause of cough, patients' detailed histories, and flexible fiberoptic endoscopy and VLS findings were reviewed. Reflux symptom index (RSI) was used for the diagnosis of gastroesophageal reflux. In RSI ≥13 group, posterior commissure edema was detected in 12 patients (42.9%), and posterior commissure hyperemia was detected in four patients (14.3%). These findings were statistically significantly higher than RSI <13 group (p=0.006 and p=0.016, respectively). No significant difference was present between the group of patients with allergic rhinitis and the group of patients without allergic rhinitis in terms of VLS findings. Mucopurulent secretion rate in posterior commissure in patients with acute sinusitis findings was statistically higher than patients without acute sinusitis findings (p<0.001). Chronic cough is a common symptom of many different diseases. Therefore, a multidisciplinary approach is important for diagnosis. Videolaryngostroboscopy is a valuable examination tool in the differential diagnosis of gastroesophageal reflux and acute sinusitis.


miR-21-3p regulates cardiac hypertrophic response by targeting histone deacetylase-8.
Growing evidences indicate that microRNAs (miRNAs) are involved in cardiac hypertrophy development. Multiple miRNAs have been identified as diagnostic and prognostic biomarkers of cardiac hypertrophy, as well as potential therapeutic tools. The present study aimed to investigate the functions and regulatory mechanisms of miR-21-3p in cardiac hypertrophy. Decreased expression of miR-21-3p was observed in cardiac hypertrophy induced by transverse aortic constriction (TAC) and angiotensin (Ang) II infusion in mice. To further explore the role of miR-21-3p in cardiac hypertrophy, rAAV-miR-21-3p was administered intravenously in mice. Overexpression of miR-21-3p markedly suppressed TAC-induced cardiac hypertrophy and also blocked Ang II-induced cardiac hypertrophy as determined by cardiac function measurement and biomarker detection. Furthermore, western blot assays showed that histone deacetylase-8 (HDAC8) was silenced by miR-21-3p, and luciferase reporter assays showed that miR-21-3p binds to the 3' UTR of HDAC8. Moreover, re-expression of HDAC8 attenuated miR-21-3p-mediated suppression of cardiac hypertrophy by enhancing phospho-Akt and phospho-Gsk3β expression. Our data reveal a role of miR-21-3p in regulating HDAC8 expression and Akt/Gsk3β pathway, and suggest that modulation of miR-21-3p levels may provide a therapeutic approach for cardiac hypertrophy.


A TIMM17A Regulatory Network Contributing to Breast Cancer.
Translocase of inner mitochondrial membrane 17A (TIMM17A) is overexpressed in breast cancer (BRCA), and upregulation can increase the aggressiveness of BRCA cells. This study examined the influence of the TIMM17A gene network on BRCA outcome. Expression levels of TIMM17A were compared between normal and tumor tissues from the OncomineTM database, and the association with patient survival was analyzed using Kaplan-Meier Plotter. Clinical factors influencing TIMM17A expression were studied by UALCAN. cBioPotal was then used to identify genes interacting with TIMM17A, and network relationships were assessed using the R clusterProfiler package. The association between TIMM17A mutation and mRNA expression in BRCA was examined using the LinkFinder application in LinkedOmics, and coexpressed genes were assessed for functional enrichment using the LinkInterpreter application. Furthermore, TIMM17A expression correlation with cell cycle phase distribution was performed by flow cytometry. Finally, the target networks of kinases, microRNAs (miRNAs), and transcription factors were identified using GeneMANIA. The expression and correlation of potential miRNAs and targets were further validated in BRCA cell lines by qRT-PCR. Expression of TIMM17A was significantly elevated in BRCA compared with normal tissue (p < 0.05), and overexpression was associated with both poor overall survival (OS) and shorter distant metastasis-free survival (DMFS) (p < 0.05). Expression of TIMM17A was not associated with age, sex, BRCA subclass, clinical stage, or patient ethnicity. The coexpressed TIMM17A network was enriched in genes targeted by cell cycle regulators such as CDK1, miR-331, and E2F family transcription factors (FDR < 0.001). Furthermore, flow cytometry revealed a strong association between higher TIMM17A expression and faster cell cycle progression in these BRCA cell lines. In addition, expression of TIMM17A protein was correlated with CDK1 protein expression in BRCA cell lines as measured by western blotting. Elevated TIMM17A expression accelerates the progression of BRCA, thereby reducing OS and DMFS. The TIMM17A-associated networks identified here provide clues to the molecular pathogenesis of BRCA and potential targets for BRCA treatment.


[Epilepsy and dreams in children].
24 patients at the age of 10-18 years with different forms of epilepsy and 10 healthy children and juveniles were examined. The analysis of dreams testified both intensification and quantitative peculiarities of dreams in epileptic patients. Their specific features were: frightening character, stereotypy, brightness and contrastness of colour images as well as psychosensory disorders and sensations of different modalities, peculiar and original topic. The dreams characteristic for epilepsy arise frequently long before the objective clinical manifestation and might serve as one of the important markers of cerebral epileptisation.


Purification and characterization of Tora-bean (Phaseolus vulgaris) lectin.
A lectin purified from the Tora-bean (Phaseolus vulgaris) by affinity chromatography with Con-A Sepharose was shown to be a glycoprotein containing 7.8% neutral sugars (D-mannose, N-acetyl-D-glucosamine, L-fucose, and D-xylose, in a molar ratio of 9.6 : 2.0 : 0.6 : 0.7). Its molecular weight was 130,000, as estimated by exclusion gel chromatography, and SDS gel electrophoresis showed that it consists of four subunits of molecular weight 32,000. The lectin reacts with various glycoproteins, i.e., blood group substances, human parotid salivary glycoprotein, fetuin, and bovine submaxillary mucin. Divalent cations, such as Ca2+, Mn2+, and Mg2+, appear to stimulate its reactivity. Inhibition tests using the glycopeptide fragment from fetuin and some oligosaccharides, as well as the binding test with 14C-N-acetyl-lactosamine suggest that the sequence of D-galactose, N-acetyl-D-glucosamine, and D-mannose residues in the carbohydrate chain of fetuin is essential for binding.


Hemoglobin and Streptococcus suis cell wall act in synergy to potentiate the inflammatory response of monocyte-derived macrophages.
Streptococcus suis, a major swine pathogen world-wide, can trigger macrophages to secrete large amounts of proinflammatory cytokines, which increase the permeability of the blood-brain barrier. In this study, we hypothesized that hemoglobin may potentiate the inflammatory response of human macrophages stimulated with a S. suis cell-wall preparation. Monocyte-derived macrophages were stimulated with the S. suis cell-wall preparation in the presence or absence of human hemoglobin, and the secretion of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 was analyzed by enzyme-linked immunosorbent assays. The cell-wall preparation induced dose-dependent IL-1beta, TNF-alpha, IL-6, and IL-8 responses in macrophages. Hemoglobin potentiated the cell-wall induced inflammatory response, resulting in a significantly higher secretion of all the cytokines. The S. suis cell-wall preparation in combination with hemoglobin activated macrophage intracellular kinases involved in inflammatory signaling pathways. In conclusion, hemoglobin, which may be released in vivo by the action of S. suis suilysin on red blood cells, contributes to raising the levels of pro-inflammatory mediators by acting in synergy with S. suis cell-wall components. This phenomenon may contribute to the development and the severity of meningitis.


Relationship between pharmacological activity and blood level of a new anticholinergic agent, timepidium bromide (SA-504), in cats.
Relationship between pharmacological activities and blood levels of a new anticholinergic agent (SA-504), as well as excretion, and distribution in the gastro-intestinal tract were investigated in cats. The time courses of inhibitory effect of SA-504 on gastric motility were closely related to those of blood levels of SA-504 after intragastric administration of 3H-labelled compound. Effects of SA-504 on the pupil of the eye, heart rate and blood pressure were much less than its inhibitory effects on gastric motility. The contents of 3H-SA-504 in the gastric wall were extremely high as compared with those in the blood and heart. About 23% of the radioactivity administered orally as 3H-SA-504 was excreted into the bile and 20% into the urine during a 24 hour period, suggesting that more than 40% of the dose is absorbed from the alimentary tract of cats within 24 hours.


Asperolide A, a marine-derived tetranorditerpenoid, induces G2/M arrest in human NCI-H460 lung carcinoma cells, is mediated by p53-p21 stabilization and modulated by Ras/Raf/MEK/ERK signaling pathway.
Here we first demonstrate that asperolide A, a very recently reported marine-derived tetranorditerpenoid, leads to the inhibition of NCI-H460 lung carcinoma cell proliferation by G2/M arrest with the activation of the Ras/Raf/MEK/ERK signaling and p53-dependent p21 pathway. Treatment with 35 μM asperolide A (2 × IC(50)) resulted in a significant increase in the proportion of G2/M phase cells, about a 2.9-fold increase during 48 h. Immunoblot assays demonstrated time-dependent inhibition of G2/M regulatory proteins. Moreover, asperolide A significantly activated MAP kinases (ERK1/2, JNK and p38 MAP kinase) by phosphorylation, and only the inhibition of ERK activation by PD98059 reversed downregulation of G2/M regulatory proteins CDC2, and suppressed upregulation of p21 and p-p53 levels. Transfection of cells with dominant-negative Ras (RasN17) mutant genes up-regulated asperolide A-induced the decrease of cyclin B1 and CDC2, suppressed Raf, ERK activity and p53-p21 expression, and at last, abolished G2/M arrest. This study indicates that asperolide A-induced G2/M arrest in human NCI-H460 lung carcinoma cells relys on the participation of the Ras/Raf/MEK/ERK signaling pathway in p53-p21 stabilization. An in vivo study with asperolide A illustrated a marked inhibition of tumor growth, and little toxcity compared to Cisplatin therapy. Overall, these findings provide potential effectiveness and a theoretical basis for the therapeutic use of asperolide A in the treatment of malignancies.


Opportunistic blood lead testing in a paediatric inpatient population.
We report a simple protocol which has potential to estimate community paediatric blood lead levels using opportunistic testing. Permission to use leftover blood for a lead assay was sought from parents or guardians of 397 children one month to 13 years of age who were admitted to general paediatric wards of John Hunter Hospital, Newcastle, between May and August 1993 and who had blood for a full blood count taken for any reason. Results were reviewed by a medical officer and returned to parents. Where a child's blood lead level was of concern according to National Health and Medical Research Council guidelines, the child was referred to a specialist paediatrician for clinical assessment. Written consent was received from the parents or guardians of 95.5 per cent of eligible children (n = 379); 93.4 per cent of responders (354 of 379) had blood suitable for testing, giving an overall result rate of 89.2 per cent (354 of 397). The mean blood lead level for the whole group was 5.3 micrograms/dL. The highest blood lead level for any age group was 6.4 micrograms/dL in the 36 to < 60 month age group. Stratification by geographical area showed a trend in increasing blood lead with increasing population density and areas where lead polluting industries exist. The approximate cost per result achieved was $40. This opportunistic survey method provides a promising technique for obtaining data on community blood lead levels. It may be a practical and resource-efficient alternative to large-scale community surveys. Further studies are under way to validate the method as a community surveillance tool.


[The primary radiotherapy of inoperable or recurrent pancreatic carcinoma--Heidelberg patients from 1982 to 1992].
Between 1982 and 1992, 34 patients with locally advanced or relapsed adenocarcinoma of the pancreas were treated at the Department of Radiotherapy in Heidelberg. 14 patients were treated with a combined radiochemotherapy with 5-FU, the other patients were irradiated alone. In all cases irradiation was done with high energy photons. 15 patients received an irradiation with doses between 30 and 44 Gy, and twelve patients between 45 and 66 Gy (median 50 Gy). Seven patients were treated intraoperatively during an exploration laparotomy with fast electrons (10 to 18 MeV, 15 to 20 Gy) and postoperatively with additional 30 to 41 Gy. The median survival of the patients treated with the higher doses or in combination with the IORT showed a significant advantage of nine vs. 2.9 months. There was no benefit in median survival for the patients treated with radiochemotherapy. In retrospective analysis of the percutaneous treated patient collective a pain relief was observed in nine patients. In the prospective treatment protocol of the IORT in 4/4 patients a pain relief was rapidly reached.


Unilateral craniosynostosis of the frontosphenoidal suture: a case report and a review of literature.
Frontal plagiocephaly, a rare congenital deformation of the skull, is one of the most complicated forms of craniosynostosis to treat. The difference between deformational and synostotic frontal plagiocephaly is small. Moreover, the visible deformations are sometimes misleading and may lead to a treatment delay. A multislice CT scan with 3D reconstruction is the preferred diagnostic tool to differentiate between craniosynostosis and deformational causes of plagiocephaly. Still, meticulous examination of all sutures is necessary to exclude any form of craniosynostosis and to prevent misdiagnosis. A case is presented of a 1-month-old boy with a progressive deformation of the left forehead, which was caused by a stenosis of the left frontosphenoidal suture. Surgical treatment consisted of a left fronto-orbital advancement. Furthermore, 3D stereophotogrammetry was used for long term follow up, which showed normalisation of the growth pattern of the skull. Isolated frontosphenoidal suture synostosis is a rare cause of frontal plagiocephaly with its own distinct clinical features. Accordingly, careful assessment of a 3D CT scan may reduce treatment delay. Furthermore, 3D stereophotogrammetry proved to be a radiation-free non-invasive patient-friendly method for long term follow up of a child with a skull deformation.


A New Strategy for Transcatheter Left Atrial Appendage Closure With Cerebral Embolic Protection in Patient With Left Auricular Thrombosis and Total Contraindication to Long-Term Anticoagulation.
Atrial fibrillation (AF) is the most common cardiac arrhythmia, occurring in 1%-2% of the general population. An important aspect is the treatment of AF in terms of stroke prevention. In patients with absolute contraindication to long-term anticoagulation due to high bleeding risk, a valuable alternative exists in left atrial appendage (LAA) closure. Unfortunately, thrombus in the LAA is a contraindication to the procedure because of high risk of embolization. We describe a clinical case with permanent AF, absolute contraindication to long-term anticoagulation therapy, and persistent thrombus formation in the LAA that was treated with transcatheter LAA closure and supraaortic trunk protection system in order to avoid risk of periprocedural stroke.


Mono- and dinuclear oxovanadium(V)calixarene complexes and their activity as oxidation catalysts.
The background of the investigation is constituted by reactive moieties and intermediates playing relevant roles on the surfaces of vanadiumoxide-based catalysts during the oxygenation/dehydrogenation of organic substrates. With the aim of modeling such species, a series of mono- and dinuclear charged and uncharged vanadium oxo complexes containing p-tert-butylated calix[4]arene and calix[8]arene ligands (denoted H4B and H8B' ', respectively, in the protonated forms) has been synthesized and characterized: PPh4[O=VB] ((PPh41), O=VB(OAc) (2), PPh4[O2V2HB' '] (3), and [mu-O(O=V(OMe))2B(Me2)] (4), where superscripts OAc and Me2 indicate that one or two protons of H4B are substituted by these residues, respectively. These compounds were analyzed both in solution and by means of single-crystal X-ray crystallography; it turned out that the crystal structures are retained on dissolution (2 changed only from the paco to the cone structure). In the case of 4, it could be shown that the bulk product consists of a mixture of two isomers (4t and 4c) differing in the relative positions of the vanadium-bound methoxy groups. Subsequently, all compounds were tested as catalysts for the oxidation of alcohols with O2. It turned out that the two dinuclear complexes efficiently catalyze the oxidation of 1-phenyl-1-propargyl alcohol and fluorenol; in addition, they even show some activity with respect to the oxidation of dihydroanthracene. This may hint to a higher activity of dinuclear sites on the surfaces of heterogeneous catalysts as well.


Germline and somatic KLLN alterations in breast cancer dysregulate G2 arrest.
PTEN is a well-described predisposition gene for Cowden syndrome (CS), a familial cancer syndrome characterized by a high risk of breast and other cancers. KLLN, which shares a bidirectional promoter with PTEN, causes cell cycle arrest and apoptosis. We previously identified germline hypermethylation of the KLLN promoter in 37% of PTEN mutation-negative CS/CS-like (CSL) patients. Patients with germline KLLN hypermethylation have an increased prevalence of breast and renal cancers when compared with PTEN mutation carriers. We have consequently sought to identify and characterize germline KLLN variants/mutations in CS/CSL and in apparently sporadic breast cancer patients. KLLN variants in CS/CSL patients are rare (1 of 136, 0.007%). Interestingly, among 438 breast cancer patients, 13 (3%) have germline KLLN variants when compared with none in 128 controls (P = 0.049). Patients with KLLN variants have a family history of breast cancer when compared with those without (P = 0.02). We demonstrate that germline KLLN variants dysregulate the cell cycle at G2. Of 24 breast carcinomas analyzed, 3 (13%) have somatic KLLN hemizygous deletions, with somatic loss of the wild-type allele in a patient with germline KLLN p.Leu119Leu. Of 452 breast carcinomas in The Cancer Genome Atlas project, 93 (21%) have KLLN hemizygous or homozygous deletions. This is the first study to associate germline KLLN variants with sporadic breast cancer and to recognize somatic KLLN deletions in breast carcinomas. Our observations suggest that KLLN may be a low penetrance susceptibility factor for apparently sporadic breast cancer.


Experiential influences on multimodal perception of emotion.
The impact of 2 types of learning experiences on children's perception of multimodal emotion cues was examined. Children (aged 7-12 years) were presented with conflicting facial and vocal emotions. The effects of familiarity were tested by varying whether emotions were presented by familiar or unfamiliar adults. The salience of particular emotional expressions was tested by contrasting the performance of physically abused and nonabused children. Children exhibited a preference for auditory expressions produced by their mothers but not by strangers. Additionally, abused children were biased to rely on auditory cues when their own abusive mother was expressing anger. These results are discussed in terms of the impact of both typical and atypical early experiences on the development of emotion perception.


Free Energy Calculations using a Swarm-Enhanced Sampling Molecular Dynamics Approach.
Free energy simulations are an established computational tool in modelling chemical change in the condensed phase. However, sampling of kinetically distinct substates remains a challenge to these approaches. As a route to addressing this, we link the methods of thermodynamic integration (TI) and swarm-enhanced sampling molecular dynamics (sesMD), where simulation replicas interact cooperatively to aid transitions over energy barriers. We illustrate the approach by using alchemical alkane transformations in solution, comparing them with the multiple independent trajectory TI (IT-TI) method. Free energy changes for transitions computed by using IT-TI grew increasingly inaccurate as the intramolecular barrier was heightened. By contrast, swarm-enhanced sampling TI (sesTI) calculations showed clear improvements in sampling efficiency, leading to more accurate computed free energy differences, even in the case of the highest barrier height. The sesTI approach, therefore, has potential in addressing chemical change in systems where conformations exist in slow exchange.


Use of monoclonal antibodies to dissect specificity and pathogenesis of antiphospholipid antibodies.
Monoclonal antiphospholipid antibodies (aPL) have been utilized to dissect the relationship between their sequence, structure, binding and biological properties relevant to the pathogenesis of the antiphospholipid syndrome. In particular, sequence analysis of aPL has highlighted the clustering of certain amino acid residues in the antigen contact sites of their heavy and light chains. Therefore, these sequence motifs are likely to be important in determining aPL binding properties and their pathogenic effects. Experiments, however, using monoclonal aPL engineered to contain specific point mutations in their sequence which alter their ability to bind relevant antigens have shown that these alterations in binding are not directly mirrored by their pathogenic effects. In this review we focus on work carried out by others and ourselves using monoclonal antibodies with specific binding properties to extend our knowledge of the non-linear structure-binding-function relationship of aPL.