The Evidence for a Causal Link Between Disease and Damaging Behavior in Pigs.
Damaging behaviors (DB) such as tail and ear biting are prevalent in pig production and reduce welfare and performance. Anecdotal reports suggest that health challenges increase the risk of tail-biting. The prevalence of tail damage and health problems show high correlations across batches within and between farms. There are many common risk factors for tail-biting and health problems, notably respiratory, enteric and locomotory diseases. These include suboptimal thermal climate, hygiene, stocking density and feed quality. The prevalence of tail damage and health problems also show high correlations across batches within and between farms. However, limited evidence supports two likely causal mechanisms for a direct link between DB and health problems. The first is that generalized poor health (e.g., enzootic pneumonia) on farm poses an increased risk of pigs performing DB. Recent studies indicate a possible causal link between an experimental inflammation and an increase in DB, and suggest a link between cytokines and tail-biting. The negative effects of poor health on the ingestion and processing of nutrients means that immune-stimulated pigs may develop specific nutrient deficiencies, increasing DB. The second causal mechanism involves tail-biting causing poor health. Indirectly, pathogens enter the body via the tail lesion and once infected, systemic spread of infection may occur. This occurs mainly via the venous route targeting the lungs, and to a lesser extent via cerebrospinal fluid and the lymphatic system. In carcasses with tail lesions, there is an increase in lung lesions, abscessation, arthritis and osteomyelitis. There is also evidence for the direct spread of pathogens between biters and victims. In summary, the literature supports the association between poor health and DB, particularly tail-biting. However, there is insufficient evidence to confirm causality in either direction. Nevertheless, the limited evidence is compelling enough to suggest that improvements to management and housing to enhance pig health will reduce DB. In the same way, improvements to housing and management designed to address DB, are likely to result in benefits to pig health. While most of the available literature relates to tail-biting, we suggest that similar mechanisms are responsible for links between health and other DB.


[Normal and abnormal cell and antibody mediated immunoreactions. Part II: The monocyte-macrophage system as a central part of cell interactions and changes in cell compartments for clinical diagnostics (author's transl)].
The immune response is a result not of one but many cellular activities. Macrophages proved to be the central part of cooperation as elucidated by in vitro lymphocyte-macrophage clusters and by the three dimensional branching lattice-work of reticular cells in vivo. Presenting antigen, inducing helper cells, producing antibodies, and activating suppressor cells is picked up briefly. Summarizing table on changing immune cell quantities in immunoproliferative and immunodeficiency syndromes is given.


Cost-Effective Production of ATP and S-Adenosylmethionine Using Engineered Multidomain Scaffold Proteins.
Adenosine triphosphate (ATP) and S-adenosyl-L-methionine (SAM) are important intermediates that are widely present in living organisms. Large-scale preparation and application of ATP or SAM is limited by expensive raw materials. To lower the production costs for ATP/SAM, in this study we used strategies applying engineered multidomain scaffold proteins to synthesize ATP and SAM. An artificial scaffold protein containing CBM3 domain, IM proteins and CL-labeled proteins was assembled to form complex 1 for catalytic reactions to increase ATP production. The ATP synthesis system produced approximately 25 g/L of ATP with approximately 15 g/L of ADP and 5 g/L of AMP using 12.5 g/L of adenosine and 40 g/L of sodium hexametaphosphate reaction at 35 °C and a pH of 8.5 for 6 h. Based on the above ATP synthesis system, two CL-labeled methionine adenosyltransferases (CL9-MAT4 and CL9-MAT5) were applied to construct scaffold protein complex 2 to achieve SAM synthesis. Approximately 25 μg of MAT4 in a reaction system with 0.3 M MgCl2 catalyzed at 20 °C and a pH of 8 catalyzed 0.5 g/L of l-Met to produce approximately 0.9 g/L of SAM. Approximately 25 μg of MAT5 in a reaction system with 0.7 M MgCl2 catalyzed at 35 °C and a pH of 8 catalyzed 0.5 g/L of l-Met to produce approximately 1.2 g/L of SAM. Here, we showed that low-cost substrates can be efficiently converted into high-value additional ATP and SAM via multi-enzyme catalytic reactions by engineered multidomain scaffold proteins.


Effect of early enteral nutrition on laparoscopic common bile duct exploration with enhanced recovery after surgery protocols.
Protocols for enhanced recovery after surgery (ERAS) provide comprehensive and evidence-based guidelines to improve perioperative care. It remains elusive whether early enteral nutrition (EEN) will play an active role in the ERAS protocols. Laparoscopic common bile duct exploration (LCBDE) is a safe and efficient method to treat patients with bile duct stones. This study aims to assess the safety, tolerability, and outcomes of EEN after LCBDE. From January 2014 to April 2017, a total of 100 patients with postoperative LCBDE were chosen and randomly divided into control group and EEN group. Patients in the control group were treated with traditional management with regular diet when tolerated, while patients in the EEN group were fed with EEN 3 h after LCBDE. The patients' characteristics, time to first flatus, complications, hospitalization stay, and hospitalization expenses were assessed and compared between patients in these two groups. EEN accelerated the recovery of gastrointestinal function, being indicated by reduced time to first flatus when compared with control group (P = 0.00). In accordance, the quick recovery of gastrointestinal function resulted in shorter hospitalization stay for the EEN group (P = 0.00); however, no significant difference was shown when comparing the hospitalization expenses. On another hand, early oral feeding increased the occurrence of abdominal distension and diarrhea complications (P = 0.00 and P = 0.03). EEN effectively improves gastrointestinal function, but raises complications such as abdominal distension and diarrhea after LCBDE. It is recommended to implement the EEN as early as possible if the patients are reasonably expected to have high compliance.


Dietary antibiotics decrease taurine loss in cats fed a canned heat-processed diet.
In a crossover design, cats were fed a canned heat-processed diet (18 g dry matter/kg initial body wt) either with (+) or without (-) antibiotics [a mixture of penicillin G, procaine (25 mg/18 g diet) and tetracycline (50 mg/18 g diet)]. The (-/+) group received no antibiotics during the first 5-wk period and received antibiotics during the second 5-wk period; the (+/-) group received the reverse. Plasma, whole blood, urinary and fecal concentrations of taurine, fecal bile acid excretion and cholyltaurine hydrolase activities were measured. Consumption of antibiotics for 5 wk resulted in a lower rate of depletion of plasma taurine. Taurine concentrations decreased more over the first 5 wk in cats in the (-/+) group than in cats in the (+/-) group [from 116 +/- 26 to 26 +/- 6 mumol/L (-/+) and from 109 +/- 6 to 77 +/- 7 mumol/L (+/-) for plasma, and from 546 +/- 8 to 292 +/- 29 mumol/L (-/+) and from 560 +/- 11 to 431 +/- 20 mumol/L (+/-) for whole blood]. Urinary total taurine excretions during the 5th week were 54 mumol/d for the (-/+) group and 135 mumol/d for the (+/-) group (pooled SEM, +/- 13). Fecal total taurine excretions during the 5th week were 184 and 53 mumol/d for the (-/+) and (+/-) groups, respectively, (pooled SEM +/- 9). Most of the fecal taurine was unconjugated (free). Fecal bile acid excretions during the 5th week were 235 +/- 18 and 106 +/- 11 mumol/d for the (-/+) and (+/-) groups, respectively. Dietary antibiotics suppressed fecal cholyltaurine hydrolase activity of cats. Fecal cholyltaurine hydrolase activities during the 5th week were 279 +/- 54 and 42 +/- 10 nmol cholic acid released.min-1.g dry feces-1 in the (-/+) and (+/-) groups, respectively. After the crossover, mean values for the groups were reversed, showing that the observed changes were due to the antibiotic treatment. These results support the hypothesis that the dietary taurine requirement of cats is largely determined by the extent of microbial degradation of taurine in the gastrointestinal tract.


Lean mass influences overnight changes in hydration, blood pressure and strength in community-dwelling older women.
We evaluated the hypothesis that greater lean mass promotes better overnight hydration, improved postural blood pressure and greater strength. Thirty women, aged 71 ± 0.9 years (mean ± SE), completed one measurement in a euhydrated state and another the following morning after an overnight fast. Measurements included hydration, lean mass, orthostatic blood pressure and strength. Participants were grouped by fat-free mass index (FFMI), with cut-points defined as low (< 15.0 kg/m(2)) and normal (≥ 15.0 kg/m(2)). Women with normal FFMI had significantly greater hydration (p < 0.01), lean mass (p < 0.001) and upper body strength (p < 0.05), while those with low FFMI had more unstable blood pressure. On day 1, women with low FFMI experienced significant postural systolic blood pressure changes from sitting to standing (-11.3 ± 4.0 mmHg, p < 0.05). On day 2, they experienced significant systolic changes from lying to sitting (-8.0 ± 2.2 mmHg, p < 0.01) and sitting to standing (-14.9 ± 5.5 mmHg, p < 0.05), and diastolic changes from lying to sitting (-8.9 ± 2.8 mmHg, p < 0.05). In conclusion, overnight fluid shifts in older women with low lean mass result in unstable postural blood pressure and loss of strength that increases the risk for early morning falls.


Are Australian smokers interested in using low-nitrosamine smokeless tobacco for harm reduction?
To determine (1) whether Australian smokers are aware of low-nitrosamine smokeless tobacco (LNSLT) products and (2) whether they would be interested in using LNSLT either as a long-term substitute for smoking or as an aid to quitting, if these products were to become legally available. 401 daily smokers were recruited by a market research company to complete an internet questionnaire about their smoking history, knowledge of smokeless tobacco and intentions to purchase LNSLT under different scenarios. Just under half (48%) indicated they were willing to buy an LNSLT product. Predictors of an interest in purchasing LNSLT were low income, poorer health, prior SLT use, belief that SLT is less harmful than cigarettes, switching to a lower tar cigarette in the past year, ever using nicotine replacement therapy products for quitting or other reasons, having made a failed cessation attempt in the previous year and not planning to quit smoking. Analysis of quitting and LNSLT purchasing intentions under different scenarios suggest that making LNSLT available at a much lower cost than smoked cigarettes while increasing taxes on cigarettes could provide a greater reduction in the number of smokers than the same tax increase alone. These results support further examination of the potential for LNSLT to reduce smoking-related harm in Australia.


Effects of time of testing, stress level, and number of conditioning days on naloxone sensitivity of conditioned stress-induced analgesia in rats.
Controversy exists as to whether conditioned stress-induced analgesia (CSIA) utilizes opioid or nonopioid mechanisms. In two experiments, both an anticipatory conditioned stimulus (CS) and a shock-associated CS were used. The duration of exposure to the anticipatory CS was long, as in studies reporting opioid CSIA, whereas the duration of the shock-associated CS was short, as in studies reporting nonopioid CSIA. In addition, the effects of unconditioned stimulus (UCS) strength were investigated by using three levels of footshock (no, moderate, and high), and the development of CSIA was monitored by using different levels of training (1 to 6 days). CSIA, measured in both anticipatory and postexposure test periods, was found to be relatively stable across tail-flick trials within days and insensitive to strength of shock. As training progressed, CSIA increased with repeated CS-UCS pairings. We tested for opioid involvement using naloxone and found opioid and nonopioid mechanisms underlying CSIA; these mechanisms combined to form a stable level of analgesia. Our data suggest that stress level and amount of training interact to activate opioid and nonopioid mechanisms of CSIA. Apparent discrepancies in previous studies regarding naloxone sensitivity of CSIA may therefore be attributable to differences in stress levels, test periods and durations of exposure to shock-related cues.


Planar Rayleigh scattering results in helium-air mixing experiments in a Mach-6 wind tunnel.
Planar Rayleigh scattering measurements with an argon-fluoride excimer laser are performed to investigate helium mixing into air at supersonic speeds. The capability of the Rayleigh scattering technique for flow visualization of a turbulent environment is demonstrated in a large-scale, Mach-6 facility. The detection limit obtained with the present setup indicates that planar, quantitative measurements of density can be made over a large cross-sectional area (5 cm x 10 cm) of the flow field in the absence of clusters.


Environmental gradients and the evolution of tri-trophic interactions.
Long-standing theory predicts herbivores and predators should drive selection for increased plant defences, such as the specific production of volatile organic compounds for attracting predators near the site of damage. Along elevation gradients, a general pattern is that herbivores and predators are abundant at low elevation and progressively diminish at higher elevations. To determine whether plant adaptation along such a gradient influences top-down control of herbivores, we manipulated soil predatory nematodes, root herbivore pressure and plant ecotypes in a reciprocal transplant experiment. Plant survival was significantly higher for low-elevation plants, but only when in the presence of predatory nematodes. Using olfactometer bioassays, we showed correlated differential nematode attraction and plant ecotype-specific variation in volatile production. This study not only provides an assessment of how elevation gradients modulate the strength of trophic cascades, but also demonstrates how habitat specialisation drives variation in the expression of indirect plant defences.


[The spleno-cytotoxic test--an indicator of toxemia in oncologic patients].
Biologic integral methods for indication of blood toxicity, the migration activity of intact donor leukocytes in agar, and the splenocytotoxic test were used in radiotoxemia assessment in 62 oncologic patients with radiation reactions and in studies on the efficacy of detoxifying therapy with polyvisoline, a new blood substitute, in 25 subjects. Both the methods for studies of the blood serum toxicity were found sufficiently informative and unsophisticated, but the splenocytotoxic test proved to be more sensitive, simple, and rapid.


CD271 mediates stem cells to early progeny transition in human epidermis.
CD271 is the low-affinity neurotrophin (p75NTR) receptor that belongs to the tumor necrosis factor receptor superfamily. Because in human epidermis, CD271 is predominantly expressed in transit-amplifying (TA) cells, we evaluated the role of this receptor in keratinocyte differentiation and in the transition from keratinocyte stem cells (KSCs) to progeny. Calcium induced an upregulation of CD271 in subconfluent keratinocytes, which was prevented by CD271 small interfering RNA. Furthermore, CD271 overexpression provoked the switch of KSCs to TA cells, whereas silencing CD271 induced TA cells to revert to a KSC phenotype, as shown by the expression of β1-integrin and by the increased clonogenic ability. CD271(+) keratinocytes sorted from freshly isolated TA cells expressed more survivin and keratin 15 (K15) compared with CD271(-) cells and displayed a higher proliferative capacity. Early differentiation markers and K15 were more expressed in the skin equivalent generated from CD271(+) TA than from those derived from CD271(-) TA cells. By contrast, late differentiation markers were more expressed in skin equivalents from CD271(-) than in reconstructs from CD271(+) TA cells. Finally, skin equivalents originated from CD271(-) TA cells displayed a psoriatic phenotype. These results indicate that CD271 is critical for keratinocyte differentiation and regulates the transition from KSCs to TA cells.


Detecting and profiling tissue-selective genes.
The widespread use of DNA microarray technologies has generated large amounts of data from various tissue and/or cell types. These data set the stage to answer the question of tissue specificity of human transcriptome in a comprehensive manner. Our focus is to uncover the tissue-gene relationship by identifying genes that are preferentially expressed in a small number of tissue types. The tissue selectivity would shed light on the potential physiological functions of these genes and provides an indispensable reference to compare against disease pathophysiology and to identify or validate tissue-specific drug targets. Here we describe a systematic computational and statistical approach to profile gene expression data to identify tissue-selective genes with the use of a more extensive data set and a well-established multiple-comparison procedure with error rate control. Expression data of 35,152 probe sets in 97 normal human tissue types were analyzed, and 3,919 genes were identified to be selective to one or a few tissue types. We presented results of these tissue-selective genes and compared them to those identified by other studies.


Evaluation and management of Carney's complex: an illustrative case.
Carney's complex is characterized by cardiac and cutaneous myxomas, mammary myxoid fibroadenomas, spotty mucocutaneous pigmentation, primary pigmented adrenocortical disease, large-cell calcifying Sertoli cell tumors of the testis, growth hormone-secreting pituitary adenomas, and psammomatous melanotic schwannomas. We present an illustrative case of Carney's complex in a 26-year-old woman who at age 20 underwent bilateral adrenalectomy for Cushing's syndrome. Six years later, she suffered multiple central nervous system embolic episodes secondary to three cardiac myxomas, which led to her death. Appropriate evaluation and management of patients with Carney's complex is outlined.


Temperature characteristics and adaptive potential of wheat ribosomes.
The translational efficiency of wheat ribosomes was studied as a function of an in vivo temperature pretreatment of wheat seedlings (Triticum aestivum L.). Ribosomes were isolated from heat-pretreated (36 degrees C) and reference (4 degrees C, 20 degrees C) wheat seedlings. The efficiency of the ribosomes in translating polyuridylic acid was assayed. Ribosomes from heat-pretreated seedlings exhibit a threefold enhanced incorporation rate of phenylalanine as compared to ribosomes from wheat seedlings adapted to 20 or 4 degrees C. This difference develops within 24 hours after onset of the heat treatment of seedlings following a 3 hour lag phase. The temperature induced changes can be traced back to the cytoplasmic ribosomes, since cycloheximide inhibits translation almost completely. Thermal inactivation of ribosomes occurs at 45 degrees C, irrespective of the temperature pretreatment of the wheat seedlings. Specific differences in the yield of ribosomes, in the polyribosomal profiles, and in the apparent Arrhenius' activation energy of protein synthesis were observed depending on the age and the temperature pretreatments. The results presented here are considered an important molecular correlation to phenotypical temperature adaptation of in vivo protein synthesis in wheat (M Weidner, C Mathée, FK Schmitz 1982 Plant Physiol 69: 1281-1288).


A Pilot Study of Younger Sibling Adaptation: Contributions of Individual Variables, Daily Stress, Interparental Conflict and Older Sibling's Variables.
Older siblings are powerful socialization agents, playing a significant role in the sociocognitive, social, and emotional development of their younger siblings. However, there are few clues about the variables that explain younger sibling's adaptation. The objective of this pilot study was to identify the determinants of younger siblings' adaptation and to analyze the role played by personal, sibling, family and older siblings' variables using 50 dyads of siblings aged between 7 and 18 years. The variables considered were the sibling relationships and the maladaptation of older siblings, and individual (sex, number of siblings, extroversion, and agreeableness) and contextual variables (interparental conflict, daily stress) were controlled. Hierarchical multiple regressions provided evidence in favor of the model that analyzed the younger siblings' maladaptation to school, showing positive associations both with the older siblings' level of school maladaptation and with sibling conflict. In addition, the study highlighted the relevance of the trait of agreeableness and of family stress in the adaptation of younger siblings.


Genetic Basis of Antigenic Variation of SAT3 Foot-And-Mouth Disease Viruses in Southern Africa.
Foot-and-mouth disease (FMD) continues to be a major burden for livestock owners in endemic countries and a continuous threat to FMD-free countries. The epidemiology and control of FMD in Africa is complicated by the presence of five clinically indistinguishable serotypes. Of these the Southern African Territories (SAT) type 3 has received limited attention, likely due to its restricted distribution and it being less frequently detected. We investigated the intratypic genetic variation of the complete P1 capsid-coding region of 22 SAT3 viruses and confirmed the geographical distribution of five of the six SAT3 topotypes. The antigenic cross-reactivity of 12 SAT3 viruses against reference antisera was assessed by performing virus neutralization assays and calculating the r1-values, which is a ratio of the heterologous neutralizing titer to the homologous neutralizing titer. Interestingly, cross-reactivity between the SAT3 reference antisera and many SAT3 viruses was notably high (r1-values >0.3). Moreover, some of the SAT3 viruses reacted more strongly to the reference sera compared to the homologous virus (r1-values >1). An increase in the avidity of the reference antisera to the heterologous viruses could explain some of the higher neutralization titers observed. Subsequently, we used the antigenic variability data and corresponding genetic and structural data to predict naturally occurring amino acid positions that correlate with antigenic changes. We identified four unique residues within the VP1, VP2, and VP3 proteins, associated with a change in cross-reactivity, with two sites that change simultaneously. The analysis of antigenic variation in the context of sequence differences is critical for both surveillance-informed selection of effective vaccines and the rational design of vaccine antigens tailored for specific geographic localities, using reverse genetics.


Fractures of the limbs complicated by ischaemia due to lesions of the major vessels.
The authors present their case material of 68 patients who had substained fractures of the limbs complicated by arterial lesions. Orthopaedic and vascular surgery should be performed within the shortest possible period of time, preferably within 12 hours of injury, and in certain severe arterial injuries within 4 hours. Osteosynthesis was performed in all cases prior to the arterial repair; in the authors' opinion this brief prolongation of the period of ischaemia has no effect on the general outcome of treatment. In the light of the results obtained, they believe that osteosynthesis should be performed with intramedullary nails in preference to plates. They found that the least satisfactory results were obtained in fractures of the lower two thirds of the tibia and fibula with lesions of the tibial arteries which at this level show characteristics typical of terminal arteries.


[Spectral characteristics of sesquiterpene pyridine alkaloids from Tripterygium plants].
Sesquiterpene pyridine alkaloids are important components in Tripterygium plants, possessing a wide range of pharmacological activities, such as anti-inflammation immunosuppression, anti-tumor, anti-virus, and deinsectization, and are of great research value. They are composed of highly oxidized dihydro-β-furansquiterpene and pyridine dicarboxylic acid through ester bonds. According to the structural characteristics of pyridine dicarboxylic acid fragments, they can be divided into various structural subtypes. Up to now, more than 110 sesquiterpene pyridine alkaloids have been isolated and identified from Tripterygium plants. This study reviewed the structural features and spectral(i.e., UV, IR, MS, and NMR) characteristics of sesquiterpene pyridine alkaloids and summarized the structural elucidation process in detail to provide references for their further research and development.


The Combined Effects of Environmental Conditioning and Sustained Load on Mechanical Properties of Wet Lay-Up Fiber Reinforced Polymer.
The aim of this study was to investigate the combined effects of an aggressive environment and sustained load on the mechanical properties of wet lay-up fiber reinforced polymers (FRP). A total of 390 specimens, including 234 carbon fiber reinforced polymer (CFRP) specimens and 156 glass fiber reinforced polymer (GFRP) specimens, were exposed to freeze⁻thaw cycles, hygrothermal aging, and wet⁻dry cycles either in an unstressed state or loaded to about 30% or 60% of the initial ultimate load. Uniaxial tension tests were conducted on the samples after specific exposure time as well as on the control samples; and tensile properties were measured for each specimen. The results showed that the three environmental exposures, particularly hygrothermal aging, led to a significant decrease in tensile strength and elongation of the CFRP and GFRP specimens even for relatively short conditioning periods, and this decrease was markedly exacerbated by higher external loading levels. It was interesting to observe that the tensile modulus of the CFRP and GFRP specimens exhibited an excellent resistance and even appeared to increase slightly after exposure. Finally, predictive values of tensile strength based on the Arrhenius method were compared with the design values of ACI 440.2R-08 and GB 50608-2010. The results showed that both ACI 440.2R-08 and GB 50608-2010 were too conservative and significantly underestimated the tensile strength of FRP materials after an anticipated exposure period.


A survey of physical methods for studying nuclear mechanics and mechanobiology.
It is increasingly appreciated that the cell nucleus is not only a home for DNA but also a complex material that resists physical deformations and dynamically responds to external mechanical cues. The molecules that confer mechanical properties to nuclei certainly contribute to laminopathies and possibly contribute to cellular mechanotransduction and physical processes in cancer such as metastasis. Studying nuclear mechanics and the downstream biochemical consequences or their modulation requires a suite of complex assays for applying, measuring, and visualizing mechanical forces across diverse length, time, and force scales. Here, we review the current methods in nuclear mechanics and mechanobiology, placing specific emphasis on each of their unique advantages and limitations. Furthermore, we explore important considerations in selecting a new methodology as are demonstrated by recent examples from the literature. We conclude by providing an outlook on the development of new methods and the judicious use of the current techniques for continued exploration into the role of nuclear mechanobiology.


Broncholith removal using the YAG laser.
An 85-year-old woman presented with a broncholith in the intermediate bronchus that could not be extracted with either flexible or rigid bronchoscopes. A YAG laser was used to fragment this broncholith so that it could be removed in pieces through a bronchoscope. Chemical composition and morphology of the broncholith were determined. Fragmentation of the large, impacted broncholith with the laser eliminated the necessity for a thoracotomy in this elderly woman.


Effects of Prenatal Nicotine, THC, or Co-Exposure on Cognitive Behaviors in Adolescent Male and Female Rats.
Although there has been a decrease in the prevalence of tobacco smoking, exposure to nicotine during pregnancy remains a substantial problem worldwide. Further, given the recent escalation in e-cigarette use and legalization of cannabis, it has become essential to understand the effects of nicotine and cannabinoid co-exposure during early developmental stages. We systematically examined the effects of nicotine and/or THC prenatal exposure on cognitive behaviors in male and female offspring. Dams were exposed to nicotine vape or vehicle, and oral edible THC or vehicle, throughout pregnancy. Adolescent offspring were then tested in the prepulse inhibition test, novel object recognition task, and novelty suppressed feeding task. At birth, pups from mothers exposed to nicotine vape or oral THC exhibited reduced body weight, compared to control pups. Prenatal nicotine vape exposure resulted in a decreased baseline startle reactivity in adolescent male and female rats, and in females, enhanced sensorimotor gating in the prepulse inhibition test. Prenatal nicotine and THC co-exposure resulted in significant deficits in the prepulse inhibition test in males. Deficits in short-term memory were also found in males prenatally exposed to THC, either alone or with nicotine co-exposure, and in females exposed to THC alone. Finally, in males, a modest increase in anxiety-associated behaviors was found with THC or nicotine exposure in the latency to approach a novel palatable food. These studies demonstrate differential effects of prenatal exposure to e-cigarette nicotine vape and/or edible THC on cognitive function, with differing effects within male and female groups. These studies demonstrate an impact of nicotine, THC, or co-exposure during early developmental stages in utero on behavioral outcomes in adolescence. These findings have important translational implications given the continued use of nicotine and THC containing products by pregnant women worldwide, which can be applied to support healthcare and policy efforts restricting nicotine and THC use during pregnancy.


The TLC-NOSF (Technology Lipido-Colloid Plus Nano-Oligo Saccharide Factor) protease inhibitor for the treatment of ulceration in rheumatic disease A case report.
Cutaneous Lupus Erithematosus is one of the most common manifestation of Systemic Lupus Erithematosus and can be featured by the onset of cutaneous vasculitis which can bring to skin ulcers, expecially on the extremities. The "common" aetiopathogenesis can be summarized as following: 1) an antiself response to the endothelial cells which brings to frequent ischemic or thrombotic episodes, 2) the drugs therapy; recently authors have been demostrated a correlation between Metalloproteinase Matrix (MMP) and Cutaneous LES. Here we present the case of a 33 y.o. woman affected by a rheumatic disorder, which has developed a chronic ulcer on her left leg. After several and different unsuccessful approaches, as homologous and autologous skin graft, and considering both the refusal of other surgery even if enhanced by Negative Pressure Therapy and the compromised vascularization which contraindicated the use of flaps, we decided to use a dressing based on the TLC-NOSF (Technology Lipido-Colloid plus Nano-Oligo Saccharide Factor) protease inhibitor, a metalloproteinase regulator. The dressing was changed 2 times/week for the first 2 months and 1 time/week for other 2 months. The ulcer became smaller at every session and we obtained a full coverage at 4th month. KEY WORDS: Nano-oligo saccharide factor, Wound.


Utility and efficiency of methacholine challenge testing in evaluating pediatric asthma: unraveling the diagnostic conundrum.
Interpretation of methacholine challenge testing (MCT) results depends on the patient's pretest probability of asthma as well as the provocative concentration (PC20); however, ordering providers rarely understand the complexity associated with its interpretation. This study investigated the clinical utility and efficiency of MCT at a tertiary center in evaluating pediatric asthma. Retrospective chart review was done for all MCT done at a tertiary center over a six year period (2011-2017). Demographics, referring provider, referral diagnosis, current symptoms with and without exercise, and baseline spirometry were collected. Pretest probability of asthma was assigned by author (RB) who was blinded to MCT results and PC20. Post-test probability of asthma was assigned based on pretest probability, MCT result (+/-), and PC20. Three assigned asthma probability categories were "unlikely" "likely", and "very likely". Of 172 subjects (91 Females, age range 5-21 years), 64.9% of MCT results (n = 111)) were negative and 35.1% (n = 60)) were positive. One was inconclusive. Those who tested positive were shorter, lighter, younger and had lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio than those who tested negative (p < 0.05). Subjects with exercise symptoms only were less likely to test positive (OR 0.2, CI 0.1-0.5). In a majority of subjects (91.8%; 157/171), MCT increased the certainty of presence or absence of asthma. In our subject population, MCT could be useful in evaluating pediatric asthma if subject's pretest probability of asthma and PC20 was taken into account. It was not as useful for subjects with exercise symptoms only.


Loss of ErbB2 expression in pulmonary metastatic lesions in osteosarcoma.
The c-erbB2 protooncogene is located on human chromosome 17 and encodes a 185-kilodalton transmembrane glycoprotein (ErbB2). Elevated ErbB2 expression or gene amplification has been shown to be associated with a poor prognosis in many cancers. Recently, it has been demonstrated that overexpression of the ErbB2 protein in osteosarcoma is associated with the presence of pulmonary metastasis and decreased survival. To further investigate the role of ErbB2 overexpression in pulmonary metastasis of osteosarcoma, its expression in the primary and metastatic lesions of the same osteosarcoma patients was compared. We compared the expression levels of ErbB2 receptor protein between the biopsy samples and pulmonary metastatic lesions in each of 19 patients with osteosarcoma who had not presented with metastasis at diagnosis. All archival materials from patients were retrieved and stained with monoclonal antibody CB11 to detect ErbB2 protein. The rate of overexpression was significantly lower in the pulmonary metastatic tumors than in the biopsy samples (11 versus 42%; p = 0.03). Among 8 patients who had shown increased levels of ErbB2 in the biopsy samples, 7 exhibited complete absence of ErbB2 in the pulmonary metastatic lesions. Overall loss of ErbB2 expression was noted in 14 of 19 patients as the initial tumor became metastatic. It is suggested that overexpression of ErbB2 decreases within individual osteosarcomas as they become metastatic. Overexpression of ErbB2 may not play an important role in the development of pulmonary metastases of osteosarcoma. Further data are needed before ErbB2 can be used in making clinical decisions for osteosarcoma patients.


A linearity-enhanced time-domain CMOS thermostat with process-variation calibration.
This study proposes a linearity-enhanced time-domain complementary metal-oxide semiconductor (CMOS) thermostat with process-variation calibration for improving the accuracy, expanding the operating temperature range, and reducing test costs. For sensing temperatures in the time domain, the large characteristic curve of a CMOS inverter markedly affects the accuracy, particularly when the operating temperature range is increased. To enhance the on-chip linearity, this study proposes a novel temperature-sensing cell comprising a simple buffer and a buffer with a thermal-compensation circuit to achieve a linearised delay. Thus, a linearity-enhanced oscillator consisting of these cells can generate an oscillation period with high linearity. To achieve one-point calibration support, an adjustable-gain time stretcher and calibration circuit were adopted for the process-variation calibration. The programmable temperature set point was determined using a reference clock and a second (identical) adjustable-gain time stretcher. A delay-time comparator with a built-in customised hysteresis circuit was used to perform a time comparison to obtain an appropriate response. Based on the proposed design, a thermostat with a small area of 0.067 mm2 was fabricated using a TSMC 0.35-μm 2P4M CMOS process, and a robust resolution of 0.05 °C and dissipation of 25 μW were achieved at a sample rate of 10 samples/s. An inaccuracy of -0.35 °C to 1.35 °C was achieved after one-point calibration at temperatures ranging from -40 °C to 120 °C. Compared with existing thermostats, the proposed thermostat substantially improves the circuit area, accuracy, operating temperature range, and test costs.


[The Effectiveness of a Shared Reading Program Among Parents of Newborns].
Early parent-child shared reading has been demonstrated to promote the development of literacy, reading skills and learning achievement in young children. Parent-child shared reading intervention programs may strengthen the willingness and reading competence of parents. To explore the attitudes and skills related to parent-child shared reading before and after an intervention program conducted in a nursery room and outpatient pediatric clinic. A single-group pretest-posttest quasi-experimental design was conducted. Seventy-five parents of newborns in the baby rooms from two hospitals in Hualien County were conveniently sampled. Parents who had just given birth received health education before discharge from the hospital from nurses focusing on the knowledge and skills of shared reading. Three age-matched picture books with reading fact sheets and consultation support were offered free to parents of children in three, respective, age groups (newborn, 4-months old and 6-months old) during parent-child visits to the pediatric clinic for regular health examinations and vaccinations. A self-designed questionnaire was administered to analyze the parents' demographic variables, reading environment, parents' attitudes toward parent-child shared reading, and familiarity with regard to parent-child shared reading skills. Parent-child reading attitudes were positively correlated with skill familiarity (r = .39). The presence or absence of children's books at home, the parent-child relationship, and parental reading habits explained 32.0% of the variance in parent-child shared-reading attitudes (R2 = .32). The presence or absence of children's books at home and the presence or absence of a library card for the child explained 44.0% of the variation in familiarity with co-reading skills (R2 = .44). Parent-child shared reading attitude scores (t = -5.14, p < .001) and skill familiarity of parents (t = -7.52, p < .001) both increased significantly after the intervention program. Parent-child shared reading educational intervention programs may be used to improve parental attitudes and skills related to parent-child shared reading.


Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer.
Chemotherapy for aggressive non-small-cell lung cancer (NSCLC) usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM) channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC.


Single-use flexible bronchoscopes compared with reusable bronchoscopes: Positive organizational impact but a costly solution.
There is at present no standard methodology to analyse the organizational impacts (OIs) of medical devices (MDs), and the field is still in its infancy. The aim of the present study was to assess, at a hospital level, the organizational and economic impacts of the introduction of a new MD, specifically the single-use flexible bronchoscope (FB). Both the organizational and economic impacts of the single-use FB were evaluated in comparison with the reusable FB currently used as standard practice in our institution. First, process maps were created for both devices (reusable and single use). Based on the 12 types of OI defined by Roussel et al, interviews were conducted with all stakeholders, and the positive and negative aspects of the reusable and single-use processes were analysed. In a second step, microcosting analysis was conducted to determine the most economical balance in use of the 2 technologies. Process maps highlighted the complexity of the reusable device process when compared with the single-use device process. Among the 12 types of OI, the single-use FB process scored better than the reusable FB process in 75% of cases. With the "fleet" of 15 reusable FBs available in our institution, using single-use FBs would represent an extra cost of €154 per procedure. Single-use and reusable devices would have the same cost (€232 per procedure) with a theoretical annual activity of 328 bronchoscopies, which is much lower than our current activity (1644 procedures per year). Organizational impact should be considered when assessing MDs. We show in this study that from an organizational viewpoint, there are many advantages to using single-use bronchoscopes. However, in economic impact, it is more cost-effective for our institution, with more than 1500 bronchoscopies performed annually, to use reusable devices.


Hepatitis C virus infection in patients undergoing allogeneic bone marrow transplantation.
Antibody to the recently identified hepatitis C virus was investigated in sera of 128 patients treated with allogeneic bone marrow transplantation, to determine the prevalence of HCV infection and its role in post-transplant liver complications. The overall prevalence of anti-HCV positivity was 28.6% (38/128 patients). The presence of pretransplant anti-HCV positivity (in 10/35 tested patients) did not seem to predict a more severe liver disease. In fact 8/10 anti-HCV+ and 15/25 anti-HCV- patients had elevated transaminases at BMT, and posttransplant liver failure (due to VOD or subacute hepatitis), and post-BMT rises in transaminases occurred regardless of anti-HCV serology (P = 0.6 and 0.2, respectively). In patients tested for anti-HCV after BMT (n = 128), only two (one anti-HCV+ and one anti-HCV-) experienced VOD; the number of patients in whom liver failure contributed to death was comparable in anti-HCV-positive and anti-HCV- negative patients (P = 0.4). Among 17 patients with documented posttransplant seroconversion (from anti-HCV- to anti-HCV+) the appearance of anti-HCV was concomitant with hepatitis exacerbation in 9 (53%). Histologic changes demonstrated a more severe liver damage in anti-HCV+ patients: a chronic hepatitis was diagnosed in 9/11 anti-HCV+ versus 1/7 anti-HCV- cases. Based on these observations, we conclude that hepatitis C virus has a role in liver disease in such patients, although its evaluation by the anti-HCV test is still of limited accuracy, due to low sensitivity and incomplete specificity.


Management of fatigue in persons with multiple sclerosis.
Fatigue is one of the most common symptoms of multiple sclerosis. Despite advances in pharmacological and non-pharmacological treatment, fatigue continues to be the disabling symptom in persons with MS (pwMS), affecting almost 80% of pwMS. In current practice, both pharmacological and non-pharmacological interventions are used in combination, encompassing a multi-disciplinary approach. The body of research investigating the effect of these interventions is growing. This review systematically evaluated the existing evidence on the effectiveness and safety of different interventions currently applied for the management of fatigue in person with multiple sclerosis in improving patient outcomes, to guide treating clinicians.


A relA/spoT homologous gene from Streptomyces coelicolor A3(2) controls antibiotic biosynthetic genes.
A 0.972-kilobase pair DNA fragment from Streptomyces lividans that induces the production of the blue-pigmented antibiotic actinorhodine in S. lividans when cloned on a multicopy plasmid has led to the isolation of a 4-kilobase pair DNA fragment from Streptomyces coelicolor containing homologous sequence. Computer-assisted analysis of the DNA sequence revealed three putative open reading frames (ORFs), ORF1, ORF2, and ORF3. ORF2 extends beyond the sequenced DNA fragment, and its deduced product shares no similarities with any other known proteins in the data bases. ORF3 is also truncated, and its 41-amino acid C-terminal product is identical to the S. coelicolor adenine phosphoribosyltransferase. The 847-amino acid ORF1 protein, with a predicted molecular mass of 94.2 kDa, strongly resembled the relA and spoT gene products from Escherichia coli and the homologs from Vibrio sp. strain S14, Haemophilus influenzae, Streptococcus equisimilis H46A, and Mycoplasma genitalium. Unlike these proteins, the ORF1 amino acid sequence analysis revealed the presence of a putative ATP/GTP-binding domain. A mutant was generated by deleting most of the ORF1 gene that showed an actinorhodine-nonproducing phenotype, while undecylprodigiosin and the calcium-dependent antibiotic were unaffected. The mutant strain grew at a much lower rate than the wild-type strain, and spore formation was delayed. When the gene was propagated on a low copy number vector, not only was actinorhodine production restored, but actinorhodine and undecylprodigiosin production was enhanced in both the mutant and wild-type and morphological differentiation returned to wild-type characteristics. (p)ppGpp synthetase activity was not detected in purified ribosomes from the ORF1-deleted mutant, while it was restored by complementation of this strain.


A study of dengue encephalitis with laboratory and clinical parameters in Tertiary Center of North India.
With expanding clinical spectrum of dengue fever, encephalitis has been documented with increasing frequency. The aim of this study was to investigate the incidence, predictors and prognostic factors of dengue encephalitis (DE) in the setting of dengue viruses (DENV) infection. A hospital-based prospective cohort study was carried out, which included laboratory confirmed dengue positive cases. All dengue cases were categorized into nonencephalitis or encephalitis group. We estimated DE incidence and analyzed clinical, laboratory and neuroimaging data on admission, discharge and follow-up for 3 months to assess its predictors and prognostic factors. Out of the enrolled 540 confirmed dengue cases, 27 patients had DE, representing 5% incidence. Two third of the DE patients were 20 years of age or younger, with male preponderance (81.5%). Fever, headache, and altered sensorium were present in >90% on admission. Significant predictors of encephalitis were mean body temperature during fever (P < 0.001), headache (P = 0.015), secondary dengue (P = 0.005), dengue hemorrhagic fever (P < 0.001), elevated hematocrit (P < 0.001), liver function test derangement (P < 0.05), and low platelet count (P = 0.006). Poor outcome factors for DE patients were prolonged duration of fever (P < 0.001), seizure (P = 0.002), and cerebrospinal fluid (CSF) DENV positivity (P = 0.049). One third patients died and the remainder of them recovered. An increasingly higher incidence rate with high mortality of DE is reported. Clinical and laboratory parameter along with DENV positivity in CSF can predict and prognosticate dengue encephalitis.


[Pleural biopsies and pleural drainage: interventional radiology].
Interventional radiography performed for diagnostic and therapeutic purposes enables specific orientation of the diagnostic and/or therapeutic interention under radiographic guidance. This minimally invasive approach reduces intervention related morbidity. Mortality remains exceptional. Pleural biopsies and pleural drainage are two interventional procedures performed as routine practices in many centers.


Development and specification of cerebellar stem and progenitor cells in zebrafish: from embryo to adult.
Teleost fish display widespread post-embryonic neurogenesis originating from many different proliferative niches that are distributed along the brain axis. During the development of the central nervous system (CNS) different cell types are produced in a strict temporal order from increasingly committed progenitors. However, it is not known whether diverse neural stem and progenitor cell types with restricted potential or stem cells with broad potential are maintained in the teleost fish brain. To study the diversity and output of neural stem and progenitor cell populations in the zebrafish brain the cerebellum was used as a model brain region, because of its well-known architecture and development. Transgenic zebrafish lines, in vivo imaging and molecular markers were used to follow and quantify how the proliferative activity and output of cerebellar progenitor populations progress. This analysis revealed that the proliferative activity and progenitor marker expression declines in juvenile zebrafish before they reach sexual maturity. Furthermore, this correlated with the diminished repertoire of cell types produced in the adult. The stem and progenitor cells derived from the upper rhombic lip were maintained into adulthood and they actively produced granule cells. Ventricular zone derived progenitor cells were largely quiescent in the adult cerebellum and produced a very limited number of glia and inhibitory inter-neurons. No Purkinje or Eurydendroid cells were produced in fish older than 3 months. This suggests that cerebellar cell types are produced in a strict temporal order from distinct pools of increasingly committed stem and progenitor cells. Our results in the zebrafish cerebellum show that neural stem and progenitor cell types are specified and they produce distinct cell lineages and sub-types of brain cells. We propose that only specific subtypes of brain cells are continuously produced throughout life in the teleost fish brain. This implies that the post-embryonic neurogenesis in fish is linked to the production of particular neurons involved in specific brain functions, rather than to general, indeterminate growth of the CNS and all of its cell types.


A new testis prosthesis material: polymethylmethacrylate.
Silicone has been the standard prosthesis material for the last three decades but new materials are being searched because of the known disadvantages of silicone such as migration and high cost. We wanted to test in rats whether or not polymethylmethacrylate could be an alternative to silicone. We prepared polymethylmethacrylate and silicone testis prostheses which were similar to testis size of rats. Eleven rats were implanted with polymethylmethacrylate, 11 others were implanted with a silicone prosthesis and sham operation was performed in 10 rats. Three months later the scrotums of the animals were removed with the prosthesis for a quantitative analysis of the chronic inflammation and fibrotic reaction and to measure the thickness of the capsule. Rejection and infection were not observed in any of the prosthesis-implanted rats. Both prosthesis groups displayed increased vascularization, hemosiderin accumulation and fibrotic and hyalinized tissue formation that replaced the muscle. Chronic inflammation was measured and found to be higher in the polymethylmethacrylate group and the difference was not found to be significant. The average thicknesses of the capsules around the polymethylmethacrylate and silicone groups were found to be 58.4 and 46.8 microm, respectively, and that difference was not significant again. In the short term polymethylmethacrylate was equally well tolerated, but the low cost of polymethylmethacrylate made it more advantageous.


Convergent evolution of bird-mammal shared characteristics for adapting to nocturnality.
The diapsid lineage (birds) and synapsid lineage (mammals), share a suite of functionally similar characteristics (e.g. endothermy) that are considered to be a result of their convergent evolution, but the candidate selections leading to this convergent evolution are still under debate. Here, we used a newly developed molecular phyloecological approach to reconstruct the diel activity pattern of the common ancestors of living birds. Our results strongly suggest that they had adaptations to nocturnality during their early evolution, which is remarkably similar to that of ancestral mammals. Given their similar adaptation to nocturnality, we propose that the shared traits in birds and mammals may have partly evolved as a result of the convergent evolution of their early ancestors adapting to ecological factors (e.g. low ambient temperature) associated with nocturnality. Finally, a conceptually unifying ecological model on the evolution of endothermy in diverse organisms with an emphasis on low ambient temperature is proposed. We reason that endothermy may evolve as an adaptive strategy to enable organisms to effectively implement various life-cycle activities under relatively low-temperature environments. In particular, a habitat shift from high-temperature to relatively low-temperature environments is identified as a common factor underlying the evolution of endothermy.


Photocatalytic solar tower reactor for the elimination of a low concentration of VOCs.
We developed a photocatalytic solar tower reactor for the elimination of low concentrations of volatile organic compounds (VOCs) typically emitted from small industrial establishments. The photocatalytic system can be installed in a narrow space, as the reactor is cylindrical-shaped. The photocatalytic reactor was placed vertically in the center of a cylindrical scattering mirror, and this vertical reactor was irradiated with scattered sunlight generated by the scattering mirror. About 5 ppm toluene vapor, used as representative VOC, was continuously photodegraded and converted to CO2 almost stoichiometrically under sunny conditions. Toluene removal depended only on the intensity of sunlight. The performance of the solar tower reactor did not decrease with half a year of operation, and the average toluene removal was 36% within this period.


Copper shell networks in polymer composites for efficient thermal conduction.
Thermal management of polymeric composites is a crucial issue to determine the performance and reliability of the devices. Here, we report a straightforward route to prepare polymeric composites with Cu thin film networks. Taking advantage of the fluidity of polymer melt and the ductile properties of Cu films, the polymeric composites were created by the Cu metallization of PS bead and the hot press molding of Cu-plated PS beads. The unique three-dimensional Cu shell-networks in the PS matrix demonstrated isotropic and ideal conductive performance at even extremely low Cu contents. In contrast to the conventional simple melt-mixed Cu beads/PS composites at the same concentration of 23.0 vol %, the PS composites with Cu shell networks indeed revealed 60 times larger thermal conductivity and 8 orders of magnitude larger electrical conductivity. Our strategy offers a straightforward and high-throughput route for the isotropic thermal and electrical conductive composites.


How to... select medical students: a second look.
Medical schools have the serious responsibility of choosing new students who will do well in training, and go on to become competent and ethical practitioners. Current methods of selection stress scientific and academic competence, somewhat to the detriment of other essential attributes. Among the other qualities that schools should require of applicants are character, common sense, creativity and courage.


[Visible/NIR analysis of fat, protein and water in chilled pork].
Fat, protein and water were determined by visible and NIR transmittance spectroscopy in chilled pork. After preprocessed by multiplicative scatter correction (MSC), the quantitative analysis models were developed based on the original, first derivative and second derivative spectra by using partial least squares (PLS) at the temperatures of 0-4 degrees C and 20 degrees C, respectively. By comparing the correlation coefficient (r), RMSEC, and SEP, we found that the first derivative model was the best, and the performance for 0-4 degrees C was better than that for 20 degrees C. At 0-4 degrees C and 20 degrees C, the correlation coefficients were 0.950 and 0.924 for fat, 0.713 and 0.455 for protein and 0.944 and 0.914 for water respectively, SEP values were 2.41 and 2.95 for fat, 5.44 and 4.25 for protein, and 2.37 and 2.38 for water respectively. The results showed that the visible and NIR analysis could measure the fat and water contents in chilled pork well, but was bad for protein, and this was caused by processing line of chilled pork. What's more, the spectrum offset was found in the original spectra at about 770 nm to be about 10 nm.


Non-orthogonal multiple access with phase pre-distortion in visible light communication.
Non-orthogonal multiple access (NOMA) offers a good balance between throughput and fairness for visible light communication (VLC). This work presents a phase pre-distortion method to improve the symbol error rate performance of NOMA uplink with successive interference cancellation (SIC) decoding in VLC. Both theoretical analysis and experimental evaluation have shown that the proposed phase pre-distortion method improves the bit-error-rate (BER) performance for NOMA under both low and high relative power ratios. Specifically, at low relative power ratios, the proposed method can eliminate the possible BER floors and alleviate the power ratio requirement by 2 dB at the BER of 3.8 × 10-3.


The appropriateness of current UK training in acute internal medicine.
Doctors training in Acute Internal Medicine (AIM) need to provide evidence that they can effectively manage 20 'top' and 40 'other important' acute medical presentations. However, the presentations considered important in the AIM curriculum do not have an empirical evidence base. This study compared real-life presentations against those in the AIM curriculum. Data on all presentations to the acute medical service at The Royal Free Hospital, London, were collected retrospectively for five non-consecutive weeks and prospectively for one week. Five frequently encountered presentations viz: cough, nausea and vomiting, dizziness, hyperglycaemia and lethargy were not amongst those listed as 'top' or 'other important' in the AIM curriculum. Hence, demonstration of competency in these presentations is currently not an explicit requirement.


Periodoannulenes: A Generalized Annulene-within-an-Annulene Paradigm for Combined σ and π Ring Currents.
Periodoannulene molecules and ions CxIxq in planar geometry offer examples of systems with the potential for outer σ and inner π ring-current double aromaticity, given a sufficient overlap of tangential pσ-orbital manifolds on the large atoms of the outer cycle. Previous theoretical work indicated concentric diatropic currents in the dication C6I62+. Ab initio ipsocentric calculations support an account in terms of frontier-orbital selection rules for current contributions in C6I62+ (and radical C6I6+, implicated in recent experimental work on the oxidation of periodobenzene). A σ/π analogue of the annulene-within-an-annulene model is applied here to periodo systems based on cyclooctatetraene. Model species C8I8q with charges q = 0, +1, +2, +4, -2 and structures constrained to a planar D4h symmetry exhibit maps with all combinations of σ/π con- and counter-rotation, comprising global σ ring currents on the iodine perimeter and central π ring currents on the carbocycle. All can be rationalized by the separate application of the tropicity selection rules to the two subsystems, whether in singlet or triplet states.


[Comparison of clinical efficacy among different surgical methods for presacral recurrent rectal cancer].
Objective: To investigate the efficacy and prognosis of three surgical methods for presacral recurrent rectal cancer (PRRC). Methods: A retrospective cohort study was carried out. Case inclusion criteria: (1) primary rectal cancer without distant metastasis and undergoing radical surgery; (2) patients undergoing radical surgery after the diagnosis of PRRC; (3) complete inpatient, outpatient and follow-up data. Clinical data of 47 patients meeting the above criteria who underwent operation at the Department of Gastrointestinal Surgery, The Peking University People's Hospital from January 2008 to December 2017 were reviewed and analyzed retrospectively. Of the 47 patients, 31 were male and 16 were female; the mean age was 57 years old; 9 (19.1%) were low differentiation or signet ring cell carcinoma, 38 (80.9%) were medium differentiation; 19 (40.4%) received neoadjuvant therapy. According to operative procedure, 22 patients were in the abdominal/abdominoperineal resection group, 15 in the sacrectomy group and 10 in the abdominosacral resection group. The operative data, postoperative data and prognosis were compared among the three groups. Survival curve was conducted using the Kaplan-Meier method, and log-rank test was used to compare survival difference among three groups. Results: There were no significant differences in baseline data among three groups (all P>0.05). All the 47 patients completed the radical resection successfully. The mean operation time was (4.7±2.1) hours, the median intraoperative blood loss was 600 ml, and the median postoperative hospitalization time was 17 days. Fifteen cases (31.9%) had perioperative complications, of which 3 cases were grade III-IV. There was no perioperative death. The mean operative time was (7.4±1.6) hours in the abdominosacral resection group, (4.9±1.6) hours in the abdominal/abdominoperineal resection group, and (3.0±1.1) hours in the sacroectomy group, with a significant difference (F=25.071, P<0.001). There were no significant differences in intraoperative blood loss, postoperative hospitalization days and perioperative complications among the three groups (all P>0.05). The median follow-up period of all the patients was 24 months, 12 cases (25.5%) developed postoperative dysfunction. The incidence of postoperative dysfunction in the abdominosacral resection group was 5/10, which was higher than 4/15 in the sacrectomy group and 3/22 (13.6%) in the abdominoperineal resection group with statistically significant difference (χ(2)=9.307, P=0.010). The 1-year and 3-year overall survival rates were 86.1% and 40.2% respectively. The 1-year overall survival rates were 86.0%, 86.7% and 83.3%, and the 3-year overall survival rates were 33.2%, 40.0% and 62.5% in the abdominal/abdominoperineal resection group, sacrectomy group and abdominosacral resection group, respectively, whose difference was not statistically significant (χ(2)=0.222, P=0.895). Conclusions: Abdominal/abdominoperineal resection, sacrectomy and abdominosacral resection are all effective for PRRC. Intraoperative function protection should be concerned for patients undergoing abdominosacral resection.


Comparative transcriptomics of anal fin pigmentation patterns in cichlid fishes.
Understanding the genetic basis of novel traits is a central topic in evolutionary biology. Two novel pigmentation phenotypes, egg-spots and blotches, emerged during the rapid diversification of East African cichlid fishes. Egg-spots are circular pigmentation markings on the anal fins of hundreds of derived haplochromine cichlids species, whereas blotches are patches of conspicuous anal fin pigmentation with ill-defined boundaries that occur in few species that belong to basal cichlid lineages. Both traits play an important role in the breeding behavior of this group of fishes. Knowledge about the origin, homology and underlying genetics of these pigmentation traits is sparse. Here, we present a comparative transcriptomic and differential gene expression analysis of egg-spots and blotches. We first conducted an RNA sequencing experiment where we compared egg-spot tissue with the remaining portion of egg-spot-free fin tissue using six individuals of Astatotilapia burtoni. We identified 1229 differentially expressed genes between the two tissue types. We then showed that rates of evolution of these genes are higher than average estimated on whole transcriptome data. Using quantitative real-time PCR, we found that 29 out of a subset of 46 differentially expressed genes showed an analogous expression pattern in another haplochromine species' egg-spots, Cynotilapia pulpican, strongly suggesting that these genes are involved in the egg-spot phenotype. Among these are the previously identified egg-spot gene fhl2a, two known patterning genes (hoxC12a and bmp3) as well as other pigmentation related genes such as asip. Finally, we analyzed the expression patterns of the same gene subset in two species that feature blotches instead of egg-spots, one haplochromine species (Pseudocrenilabrus philander) and one ectodine species (Callochromis macrops), revealing that the expression patterns in blotches and egg-spots are rather distinct. We identified several candidate genes that will serve as an important and useful resource for future research on the emergence and diversification of cichlid fishes' egg-spots. Only a limited degree of conservation of gene expression patterns was detected between the egg-spots of the derived haplochromines and blotches from ancestral haplochromines, as well as between the two types of blotches, suggesting an independent origin of these traits.


Application of PRVEP Waveform Amplitude Ratio to Evaluate Visual Acuity and Its Forensic Significance.
Objective To research the correlation between the visual acuity ratio and pattern reversal visual evoked potential (PRVEP) P100 waveform amplitude ratio of both eyes. Methods Forty-seven volunteers were selected, and the visual chart visual acuity of both eyes was measured. The visual acuity ratio of the eye with poor vision to the eye with better vision was calculated by five grade notation method. The amplitudes of P100 waveforms of both eyes were recorded respectively by using black-and-white checkerboard PRVEP and chosing 1°, 15' stimulating visual angle, and the ratio of amplitudes between the two eyes was also calculated. SPSS 20.0 software was used to analyze the correlation between the visual acuity ratio and the ratio of P100 waveform amplitudes between the two eyes. Return test and linear regression analysis with the binocular ratio of P100 waveform amplitudes as the independent variable (x) and the binocular visual acuity ratio as the dependent variable (y) were made. Results There was a positive correlation between the binocular visual acuity ratio and the ratio of P100 waveform amplitudes under 15' stimulating visual angle (Pearson correlation coefficient was 0.62, P=0.000). The fitting linear regression equation was y=0.090 x+0.846 (F=20.954, P=0.000). There was no significant correlation between the binocular ratio of visual acuity and the binocular ratio of P100 waveform amplitudes under 1° stimulating visual angle (P>0.05). Results of return test showed that there was no statistical significance in the difference between visual acuity estimated by equation and actual detected visual acuity. Conclusion In forensic appraisal of monocular injury, fitting linear regression equation of binocular visual acuity ratio and the binocular ratio of P100 waveform amplitudes under 15' stimulating visual angle, is helpful for visual acuity level estimation of the injured eye to some extent.


Synthesis of (2S,3R)-beta-methyltyrosine catalyzed by tyrosine phenol-lyase.
A one-step enzymatic synthesis of the conformationally restrained tyrosine analog (2S,3R)-beta-methyltyrosine is reported. This synthesis extends the preparative chemistry associated with tyrosine phenol-lyase. This beta-methyltyrosine derivative was shown to be an efficient protein tyrosine kinase substrate, suggesting that conformational restraint may ultimately be used to enhance tyrosine kinase recognition of substrates.


Matching bacteriological and medico-administrative databases is efficient for a computer-enhanced surveillance of surgical site infections: retrospective analysis of 4,400 surgical procedures in a French university hospital.
Our goal was to estimate the performance statistics of an electronic surveillance system for surgical site infections (SSIs), generally applicable in French hospitals. Three detection algorithms using 2 different data sources were tested retrospectively on 9 types of surgical procedures performed between January 2010 and December 2011 in the University Hospital of Nantes. The first algorithm was based on administrative codes, the second was based on bacteriological data, and the third used both data sources. For each algorithm, sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. The reference method was the hospital's routine surveillance: a comprehensive review of the computerized medical charts of the patients who underwent one of the targeted procedures during the study period. A 3,000-bed teaching hospital in western France. We analyzed 4,400 targeted surgical procedures. Sensitivity results varied significantly between the three algorithms, from 25% (95% confidence interval, 17-33) when using only administrative codes to 87% (80%-93%) with the bacteriological data and 90% (85%-96%) with the combined algorithm. Fewer variations were observed for specificity (91%-98%), PPV (21%-25%), and NPV (98% to nearly 100%). Overall, performance statistics were higher for deep SSIs than for superficial infections. A reliable computer-enhanced SSI surveillance can easily be implemented in French hospitals using common data sources. This should allow infection control professionals to spend more time on prevention and education duties. However, a multicenter study should be conducted to assess the generalizability of this method.


Barrett's esophagus in children and young adults. Frequent association with mental retardation.
Since few data are available on epidemiologic features of Barrett's esophagus in young persons, we reviewed the case records of patients undergoing esophageal biopsies at Children's Hospital, Boston, from 1982 through 1986. There were 1423 esophageal biopsies obtained from 1173 patients, and histological evidence of esophagitis was present in 397 cases; Barrett's epithelium was diagnosed in 10 patients (0.9% of total and 2.5% of esophagitis cases). Specialized columnar epithelium was present in seven of these 10 patients. The mean age of those with Barrett's epithelium was 19.0 +/- 7.9 years (range 3.7-27 years) compared to 8.7 +/- 6.7 years (range 4 days to 31 years) for all patients biopsied (P less than 0.0001); 80% (8/10) of the Barrett's cases were male compared to 54% of all cases. The relative importance of the possible risk factors was assessed by comparing the 10 patients with Barrett's with the 541 patients that had esophageal biopsies in calendar years 1984-1985. Mental retardation, a risk factor not previously described for young persons with Barrett's esophagitis, was present in 70% (7/10) of the Barrett's patients but in only 15% of all patients biopsied (P less than 0.0002). The frequency of mental retardation was also higher, but not significantly so (P greater than 0.07), in patients with biopsies that were positive for esophagitis (19%) than in those with normal biopsies (14%). No significant differences were found between the Barrett's group and all patients biopsied in regards to racial origin, prior stricture, or fundoplication.


[Community mental health networks and doors at a Health and Community Center (CeSAC No 24) in the south of the Autonomous City of Buenos Aires (CABA)].
The history of the Health and Community Center (CeSAC) No 24 began 21 years ago in the Ramón Carrillo district, in Villa Soldati neighborhood. This is a marginal urban area in the south of the CABA with a population with urgent needs. The work started with a group of professionals dealing with primary care practices, and it continues up to the present. The goal of our community mental health project is the creation of spaces for prevention and well-being including art in all its expressions, with the active participation of neighbors in the coordination of many activities. Through the symbolic opening of doors and making networks visible, we opened the CeSAC to universities, scientific societies, foundations, NGOs, neighbor committees, neighborhood boards, human rights organizations, formal and informal education centers, cultural centers, churches, community radios, in order to show the vital movements of the community, as we -as a team- are an integral part of it. Our spaces, workshops and programs are a collective socio-historical construction that achieves milestones such as thinking, thinking of us, getting together and achieving the participation from the community and the continuous training for everybody working and living in Soldati. The decentralization and democratization trend, and the heterarchical management of our organization favors the possibility of catalyzing the wishes, motivations and efforts of the healthcare team, neighbors and network nodes, thus benefiting the creative work that turns a dream into a hopeful reality.


Proteinuria in AMPD2-deficient mice.
The AMPD2 gene, a member of the AMPD gene family encoding AMP deaminase, is widely expressed in nonmuscle tissues including kidney, although its functions have not been fully elucidated. In this study, we studied the function of the AMPD2 gene by establishing AMPD2-deficient model animal. We established AMPD2 knockout mice by using gene transfer and homologous recombination in murine ES cells and studied phenotypes and functions in the kidneys of these animals. AMPD activity was decreased from 22.9 mIU/mg protein to 2.5 mIU/mg protein in the kidneys of AMPD knockout mice. In addition to changes in nucleotide metabolism in the kidneys, proteinuria was found in 3-week-old AMPD2 knockout mice, followed by a further increment up to a peak level at 6 weeks old (up to 0.6 g/dL). The major protein component in the urine of AMPD2 knockout mice was found to be albumin, indicating that AMPD2 may have a key role in glomerular filtration. Indeed, an ultrastructure study of glomerulus specimens from these mice showed effacement of the podocyte foot processes, resembling minimal-change nephropathy in humans. Based on our results, we concluded that AMPD2 deficiency induces imbalanced nucleotide metabolism and proteinuria, probably due to podocyte dysfunction.


Life expectancy in people with newly diagnosed epilepsy.
Epilepsy carries a risk of premature mortality, but little is known about life expectancy in people with the condition. The UK National General Practice Study of Epilepsy is a prospective, population-based study of people with newly diagnosed epilepsy. A cohort of 564 patients with definite epilepsy has been followed for nearly 15 years and there have been 177 deaths. These data have been used to estimate life expectancy of people in this cohort by employing a parametric survival model based on the Weibull distribution. Life expectancy in people with epilepsy was estimated as a function of age at, and time from, diagnosis according to two broad aetiological groups. These estimates were then compared with life expectancy in people of the same age and sex in the general population. Reduction in life expectancy can be up to 2 years for people with a diagnosis of idiopathic/cryptogenic epilepsy, and the reduction can be up to 10 years in people with symptomatic epilepsy. Reductions in life expectancy are highest at the time of diagnosis and diminish with time. Our model provides broad estimates, but it appears that the higher mortality rates in people with newly diagnosed epilepsy translate into decreased life expectancy.


Transport of very preterm infants with respiratory distress syndrome using nasal continuous positive airway pressure.
To audit clinical practice during transport of very preterm infants (<32 weeks) with acute respiratory distress syndrome (RDS) receiving nasal continuous positive airway pressure (NCPAP). Retrospective cohort study. Twenty-seven infants were receiving NCPAP before transport team's arrival, and 23 were commenced on NCPAP after team's arrival. Six infants (12%) failed NCPAP before transfer, 2 infants (4.5%) failed NCPAP less than 24 hours, and 5 infants (11.3%) failed more than 24 hours - 7 days following admission. None died or developed pneumothorax during, or 7 days after admission. We did not observe NCPAP failure during transfer. There was a statistically significant difference between the NCPAP success and NCPAP failure groups for FiO2 at admission (p < 0.05), and the duration of NCPAP (p < 0.05). NCPAP is a potentially safe and effective mode of respiratory support for very preterm infants during ground, and air transports.


[Gene polymorphisms of renin-angiotensin system in patients with kidney diseases].
Blockade of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, has been well appreciated as a renoprotective treatment in proteinuric glomerular diseases. However, not all patients with glomerular diseases respond well to this therapy. Single nucleotide polymorphisms (SNPs) in angiotensin-converting enzyme (ACE) and angiotensinogen may be involved in the inter-individual difference in the responsiveness to the renoprotective efficacy of the RAS blockade. This review focuses on the interface between genomics and therapeutics in the renin-angiotensin system in IgA nephropathy, the most prevalent form of primary glomerulonephritis and one of the major causes of end-stage renal disease in the world.


Synthesis and reactivity of iron-dinitrogen complexes bearing anionic methyl- and phenyl-substituted pyrrole-based PNP-type pincer ligands toward catalytic nitrogen fixation.
Iron-dinitrogen complexes bearing methyl- and phenyl-substituted pyrrole-based anionic PNP-type pincer ligands are prepared and characterized by X-ray analysis. The former complex is found to work as a more effective catalyst than that bearing a non-substituted PNP-type pincer ligand toward the transformation of nitrogen gas into ammonia and hydrazine under mild reaction conditions.


UV-vis spectroscopic studies of low-energy argon-ion-bombarded ion-exchanged glasses.
The ion-exchanged glasses bombarded with 80 eV, 100 eV, and 120 eV argon ions at room temperature are investigated. The optical and structural properties of ion-exchanged glasses before and after bombardment were analyzed by means of a UV-vis spectrometer, x-ray photoelectron spectroscopy, and electron probe micro analysis, respectively. The optical absorption and transmittance spectra of ion-exchanged glasses appear as obvious changes in the UV-visible region after bombardment. The optical absorption band and transmittance properties of ion-exchanged glasses at about 369-900 nm are less sensitive to the ion bombardment energy than that at about 200-280 nm. The changes in binding energy shift and peak area ratios of non-bridging oxygen and bridging oxygen contributions to the O 1s lines were observed with increasing ion beam bombardment energy. Accompanied with out-diffusion of potassium cations during argon ion bombardment, the peak of potassium cations concentration in the exchanged region decreases and moves into the interior of glasses in different degrees. The results show that variation of structure and optical properties of the ion-exchanged glasses are indicative of alterations of the silicate network structure induced by argon ion bombardment, which provide important information for application of the ion-exchanged glasses.


Using genome-wide association analysis to characterize environmental sensitivity of milk traits in dairy cattle.
Genotype-by-environment interaction (GxE) has been widely reported in dairy cattle. One way to analyze GxE is to apply reaction norm models. The first derivative of a reaction norm is the environmental sensitivity (ES). In the present study we conducted a large-scale, genome-wide association analysis to identify single-nucleotide polymorphisms (SNPs) that affect general production (GP) and ES of milk traits in the German Holstein population. Sire estimates for GP and for ES were calculated from approximately 13 million daughter records by the use of linear reaction norm models. The daughters were offspring from 2297 sires. Sires were genotyped for 54k SNPs. The environment was defined as the average milk energy yield performance of the herds at the time during which the daughter observations were recorded. The sire estimates were used as observations in a genome-wide association analysis, using 1797 sires. Significant SNPs were confirmed in an independent validation set (500 sires of the same population). To separate GxE scaling and other GxE effects, the observations were log-transformed in some analyses. Results from the reaction norm model revealed GxE effects. Numerous significant SNPs were validated for both GP and ES. Many SNPs that affect GP also affect ES. We showed that ES of milk traits is a typical quantitative trait, genetically controlled by many genes with small effects and few genes with larger effect. A log-transformation of the observation resulted in a reduced number of validated SNPs for ES, pointing to genes that not only caused scaling GxE effects. The results will have implications for breeding for robustness in dairy cattle.


Interaction of Gut Microbiota and Brain Function in Patients With Chronic Insomnia: A Regional Homogeneity Study.
Recent studies have shown that the human gut microbiota (GM) plays a critical role in brain function and behavior via the complex microbiome-gut-brain axis. However, knowledge about the underlying relationship between the GM and changes in brain function in patients with chronic insomnia (CI) is still very limited. In this prospective study, 31 CI patients and 30 healthy controls were recruited. Resting-state functional magnetic resonance imaging scans were performed and brain functional alterations in CI patients were evaluated using the regional homogeneity (ReHo) method. We collected fecal samples of CI patients and used 16S rDNA amplicon sequencing to assess the relative abundance (RA) and alpha diversity of the GM. We also performed extensive sleep, mood, and cognitive assessments. Then, we tested for potential associations between the GM profile, ReHo alterations, and neuropsychological changes in CI patients. Our results showed associations between the RA of Lactobacilli, ReHo values in the left fusiform gyrus, and depression scores in CI patients. We also found some bacterial genera related to ReHo values of the right triangular inferior frontal gyrus. In addition, the RA of genus Coprobacter was correlated with ReHo values of the left angular gyrus and with specific cognitive performance. These findings revealed complex relationships between GM, brain function, and behavior in patients with CI.


Artery of Percheron Infarct: ARarity Not to be Missed.
Artery of Percheron (AOP) is a rare vascular variant of posterior cerebral circulation and it supplies blood to the bilateral paramedian thalami and the rostral midbrain. Artery of Percheron infarct requires a comprehensive clinical and radiological examination. It can be easily overlooked due to normal CTfindings and wide range of differential diagnosis. Classic triad of presentation is altered mental status, memory impairment and the vertical gaze palsy. We report a case of a 66-year female who had sudden onset of severe vertigo, diplopia and ataxia. Anon-contrast CTBrain was performed which was normal. Her MRI brain with diffusion weighted images (DWI) confirmed bilateral thalamic infarcts which were initially thought to be calcifications, as usually happens with diagnosing artery of Percheron infarcts. However, by reviewing and ruling out all other possible causes of such symptoms and further review of neuroimaging, lead us to the correct diagnosis.


Individual differences in the improvement of cocaine-induced place preference response by the 5-HT2C receptor antagonist SB242084 in rats.
The 5-HT(2A) and 5-HT(2C) receptors have been shown to be differentially involved in modulating cocaine-induced behaviors. In this study we investigated the effects of the 5-HT(2A) antagonist MDL100907 (0.3 mg/kg, i.p.) and the 5-HT(2C) antagonist SB242084 (0.5 mg/kg, i.p.) on development, expression, and recall of cocaine-induced conditioned place preference (CPP) in high- (HR) and low-responder (LR) rats to novelty. First, we examined the effects of MDL100907 and SB242084 on development of cocaine-induced CPP. Our results indicated that LR, but not HR, animals conditioned with SB242084 + cocaine showed a significantly higher CPP response than controls. This effect was long lasting, as it was still present 30 days after the last conditioning session. Second, we investigated the acute effects of MDL100907 and SB242084 on CPP expression 24 h after cocaine conditioning. Again, our data showed that SB242084 significantly enhanced the expression of cocaine CPP in LR, but not HR animals. Finally, we studied the acute effects of MDL100907 and SB242084 on CPP recall 30 days after cocaine conditioning. Neither MDL100907 nor SB242084 significantly affected the CPP response regardless of the rats' behavioral phenotype. This is the first study investigating the contribution of 5-HT(2A) and 5-HT(2C) receptors on development, expression, and recall of cocaine-induced CPP in the HR-LR model of individual vulnerability to drug abuse. Our results show that SB242084 differentially modulates development and expression of CPP in HR vs. LR rats and suggest that 5-HT(2C) receptors play a key role in individual differences on cocaine reward-related learning/memory processes.


Invasive tumors derived from xenotransplanted, immortalized human cells after in vivo exposure to chemical carcinogens.
Several chemicals that are found in cigarette smoke or diesel oil engine exhausts, such as benzo[a]pyrene (B[a]P) and 1,6-dinitropyrene (DNP) are carcinogenic in experimental animal models. In the present study, we have exposed in vivo the xenotransplanted immortalized human bronchial epithelial cell line BEAS-2B to the ultimate carcinogen of B[a]P, benzo[a]pyrene diolepoxide (BPDE), to DNP or to the benzo[e]pyrene, a less active compound that has tumor-promoting abilities in mouse skin carcinogenesis bioassays. All three compounds were administered using slow-release beeswax pellets. After a 6 month exposure, BPDE produced two tumors in seven transplants, four tumors were seen in 10 transplants treated with DNP and one tumor was observed in five tracheal grafts exposed to B[a]P. All the neoplasms were well-differentiated invasive adenocarcinomas. Tracheal transplants exposed to beeswax without carcinogen did not show any evidence of neoplastic growth, and their luminal surfaces were lined by a single or double layer of cuboidal cells. All lines derived from the adenocarcinomas showed increased in vitro resistance to serum-induced terminal differentiation, gelatinolytic activity, s.c. tumorigenicity and invasive growth in an in vivo assay. When these cell lines were compared with previously described tumor cell lines derived from xenotransplants exposed to cigarette smoke condensate, it became clear that the latter exhibited a more aggressive invasive behavior. Nevertheless treatment with the three chemicals gave rise to tumor cell lines that exhibited a similar invasive behavior in vivo, and were able to penetrate early into the wall of the tracheal transplants in which they were seeded. These data indicate that this system based on xenotransplanted bronchial epithelial cells is a very relevant model to identify human carcinogens and to study mechanisms of bronchogenic cancer pathogenesis.


Intraoperative blood salvage (IOBS) in cardiac and vascular surgery.
The extensive application of IOBS has permitted a great reduction in the use of homoglous transfusion which presently represents the largest field of application of autologous systems. In cardiac and vascular surgery, IOBS is particularly useful to the goal of preventing the transmission of viral disorders and other adverse effects related to homologous transfusions. The apparatuses for IOBS may also be used to perform hemodilution and sequestration of a desired amount of platelet rich plasma. The appropriate usage of drugs in perioperative period and the promotion of hemostasis with IOBS are important costituents for the correct transfusional management of the patient. The feasibility and safety of IOBS is known and in expert hands it is an optimal method for the transfusional treatment of surgical patients.


Floc characterisation by analysis of laser beam attenuation.
The continuous growth in the demand of good quality water for different purposes makes the control of environmental pollution a matter for public and official concern. The monitoring of particles for quality control of water or wastewater treatment is becoming important and the need for the development of control devices is increasing. The purpose of this work was to develop a photosedimentation method for floc characterization combining gravitational settling with photoelectric measurements. Settling particles cross a light beam that illuminates a detection system. The attenuation of the beam is related to the projected area of the particles and so the particle size distribution can be determined. When a floc crosses the beam, the amount of light reaching the detector is reduced. Voltage/time signals are analyzed in order to produce the physical characteristics of flocs such as size and density. Different light sources and detection systems were tested in calibration tests and afterwards flocculated suspensions were used for experimental analysis. Floc characteristics could then be related to the experimental conditions of floc formation (mixing conditions and polymer concentration). With the experience acquired, a prototype was designed and implemented, being capable of operating in laboratory or field conditions.


Effect of Unsaturated Metal Site Modulation in Highly Stable Microporous Materials on CO2 Capture and Fixation.
We have designed and synthesized two unprecedented microporous three-dimensional metal-organic frameworks, {[Cd6(TPOM)3(L)6]·12DMF·3H2O}n (1) and {[Zn2(TPOM)(L)2]·2DMF·H2O}n (2), based on a flexible quadritopic ligand, tetrakis(4-pyridyloxymethylene)methane (TPOM), and a bent dicarboxylic acid, 4,4'-(dimethylsilanediyl)bis-benzoic acid (H2L). The networks of 1 and 2 share a 4-c uninodal net NbO topology but exhibit different metal environments due to coordination preferences of Cd(II) and Zn(II). The Cd(II) center in 1 is six-coordinated, whereas the Zn(II) center in 2 is only four-coordinated, making the latter an unsaturated metal center. Such modulation of coordination atmosphere of metal centers in MOFs with the same topology is possible due to diverse binding of the carboxylate groups of L2-. Both 1 and 2 have relatively high thermal stability and exhibit permanent porosity after the removal of guest solvent molecules based on variable temperature powder X-ray diffraction and gas adsorption analysis. These materials exhibit similar gas adsorption properties, especially highly selective CO2 uptake/capture over other gases (N2 and CH4). However, because of the presence of an unsaturated Lewis acidic metal site, 2 acts as a very efficient heterogeneous catalyst toward the chemical conversion of CO2 to cyclic carbonates under mild conditions, whereas 1 shows very less activity. This work provides experimental evidence for the postulate that an unsaturated metal site in MOFs enhances adsoprtion of CO2 and promotes its conversion via the Lewis-acid catalysis.


A model hypocholinergic syndrome produced by a false choline analog, N-aminodeanol.
N-aminodeanol is an analog of choline that serves as a less effective substrate in all of its known enzymatic and transport mechanisms. It was utilized to test the hypothesis that the selective vulnerability of cholinergic neurones in Alzheimer's disease is due to competition for the available choline between pathways for acetylcholine and phospholipid synthesis. Rats placed on a choline free diet containing an equivalent amount of N-aminodeanol develop a model hypocholinergic state comprising hyperreactivity, hyperalgesia, aggressive behavior and a deficit in learning and memory. These effects are associated with a progressive replacement of free and lipid-bound choline and acetylcholine with N-aminodeanol and its corresponding esters. Choline acetyltransferase is reduced in some brain regions, suggesting a loss of cholinergic neurones. We propose that this represents a potentially useful animal model of Alzheimer's disease which deserves further investigation.


An Up-to-date Assessment of US Prostate Cancer Incidence Rates by Stage and Race: A Novel Approach Combining Multiple Imputation with Age and Delay Adjustment.
In the USA, it is unknown whether metastatic prostate cancer incidence has continued to increase and whether racial differences have persisted. Combining multiple imputation with age and delay adjustment, we provide an up-to-date, comprehensive assessment of US prostate cancer incidence trends by stage and race. From Surveillance Epidemiology and End Results (SEER)-18, 774 240 prostate cancer cases were diagnosed during 2004-2017. Multiple imputation assigned prostate cancer stage to the 4.7% of cases with missing stage, which varied by year and race-ethnicity. SEER delay factors adjusted case counts to anticipated future data corrections. Twenty datasets were imputed, and Rubin's rules were used for summary estimation. Overall and stage-specific rates were estimated and stratified by race and age group. Joinpoint software identified significant temporal changes and estimated annual percentage changes. We compared these estimates without multiple imputation and delay adjustment. Metastatic prostate cancer incidence increased during 2011-2017, with an annual percentage change of 5.5. This was followed by increases in localized and regional disease since 2014. Non-Hispanic black men continued to have the highest incidence, especially for metastatic disease. The increasing rate of metastatic prostate cancer in non-Hispanic white men aged 50-74 yr accelerated recently, and the incidence was 56% higher in 2017 than in 2004. Rates without multiple imputation and delay adjustment were quantitatively and qualitatively different. This observational study is unable to assign causes to observed changes in prostate cancer incidence. Multiple imputation and delay adjustment are essential for portraying accurately stage- and race-specific prostate cancer incidence as clinical practice evolves. In the USA, diagnosis of prostate cancer that has spread to distant sites (metastatic disease) continues to increase. Black men continue to have higher risks of being diagnosed with metastatic prostate cancer than other race-ethnicities.


Effects of Carbazole Derivatives on Neurite Outgrowth and Hydrogen Peroxide-Induced Cytotoxicity in Neuro2a Cells.
Many studies have demonstrated that oxidative stress plays an important role in several ailments including neurodegenerative diseases and cerebral ischemic injury. Previously we synthesized some carbazole compounds that have anti-oxidant ability in vitro. In this present study, we found that one of these 22 carbazole compounds, compound 13 (3-ethoxy-1-hydroxy-8- methoxy-2-methylcarbazole-5-carbaldehyde), had the ability to protect neuro2a cells from hydrogen peroxide-induced cell death. It is well known that neurite loss is one of the cardinal features of neuronal injury. Our present study revealed that compound 13 had the ability to induce neurite outgrowth through the PI3K/Akt signaling pathway in neuro2a cells. These findings suggest that compound 13 might exert a neurotrophic effect and thus be a useful therapy for the treatment of brain injury.