Numerical response of predators to large variations of grassland vole abundance and long-term community changes.
Voles can reach high densities with multiannual population fluctuations of large amplitude, and they are at the base of predator communities in Northern Eurasia and Northern America. This status places them at the heart of management conflicts wherein crop protection and health concerns are often raised against conservation issues. Here, a 20-year survey describes the effects of large variations in grassland vole populations on the densities and the daily theoretical food intakes (TFI) of vole predators based on roadside counts. Our results show how the predator community responded to prey variations of large amplitude and how it reorganized with the increase in a dominant predator, here the red fox, which likely negatively impacted hare, European wildcat, and domestic cat populations. This population increase did not lead to an increase in the average number of predators present in the study area, suggesting compensations among resident species due to intraguild predation or competition. Large variations in vole predator number could be clearly attributed to the temporary increase in the populations of mobile birds of prey in response to grassland vole outbreaks. Our study provides empirical support for more timely and better focused actions in wildlife management and vole population control, and it supports an evidence-based and constructive dialogue about management targets and options between all stakeholders of such socio-ecosystems.


Gastric cancer survival and affiliation to health insurance in a middle-income setting.
To investigate whether health insurance affiliation and socioeconomic deprivation is associated with overall cause survival from gastric cancer in a middle-income country. All patients resident in the Bucaramanga metropolitan area (Colombia) diagnosed with gastric cancer between 2003 and 2009 (n=1039), identified in the population-based cancer registry, were followed for vital status until 31/12/2013. Kaplan-Meier models provided crude survival estimates by health insurance regime (HIR) and social stratum (SS). Multivariate Cox-proportional hazard models adjusting HIR and SS for sex, age and tumor grade, were performed. Overall 1 and 5 year survival proportions were 32.4% and 11.0%, respectively, varying from 49.3% and 15.8% for patients affiliated to the most generous HIR to 12.9% and 5.3% for unaffiliated patients, and from 41.4% and 20.7% for patients in the highest SS, versus 27.1% and 7.4% for the lowest SS. The multivariate analyses showed type of HIR as well as SS to remain independently associated with survival, with an 11% improvement in survival for each increase in SS subgroup (HR 0.89 (95% CI 0.83; 0.96), and with worse survival in the subsidized (least generous) HIR and unaffiliated patients compared to the contributory HIR (HR subsidized 1.20 (95% CI 1.00; 1.43) and HR not affiliated 2.03 (95% CI 1.48; 2.78)). Of the non-affiliated patients, 60% had died at the time of diagnosis, versus 4-14% of affiliated patients (p<0.0005). Despite the 'universal' health insurance system, large socioeconomic differences in gastric cancer survival exist in Colombia. Both social stratum and access to effective diagnostic and curative care strongly influence survival.


Courtship songs of Drosophila pseudoobscura and D. persimilis. II. Genetics of species differences.
Although male courtship songs have been repeatedly implicated in sexual isolation between numerous Drosophila species, no genetic studies have evaluated the genetic basis of differences between species beyond using quantitative genetic analyses of hybrids or surveying associations of song characters to five or fewer genetic markers. Here, we dissect the genetic basis of the difference between D. pseudoobscura and D. persimilis in two courtship song elements (interpulse interval and intrapulse frequency) using 15 molecular markers. We also evaluate the association between song elements and sexual isolation in these backcross hybrid males of these species. We find that song differences between these species are associated with at least two or three genomic regions, and the species difference in interpulse interval may be oligogenic. Courtship song differences are especially strongly associated with two inversions that differentiate these species. Further, we found that interpulse interval is strongly associated with mating success to D. pseudoobscura females, while intrapulse frequency is associated with mating success to D. persimilis females. Implications of these findings are discussed.


Seven lessons from the field: Research on transformation of health systems for older adults.
Research can play a key role in efforts to transform healthcare systems. Our group's long-standing research program has been aimed at understanding how to support greater integration and coordination of healthcare services for older adults with complex conditions. Drawing on this experience, we outline seven "lessons from the field" that highlight research-related challenges that may hinder health system transformation. These challenges relate to conducting research in a complex and constantly changing system; co-design approaches that are simultaneously deemed essential yet too ambiguous to fund; patient, family caregiver, and citizen engagement; limited funding for health systems research; and lack of use of research findings. We hope that these reflections will help to inform an ongoing conversation about how these challenges might be overcome.


Post-traumatic stress disorder, social anxiety disorder, and depression in survivors of the Kosovo War: experiential avoidance as a contributor to distress and quality of life.
Few studies have been conducted on psychological disorders other than post-traumatic stress disorder (PTSD) in war survivors. The aim of this study was to examine PTSD, social anxiety disorder (SAD), and major depressive disorder (MDD) and their associations with distress and quality of life in 174 Albanian civilian survivors of the Kosovo War. This included testing of conceptual models suggesting that experiential avoidance might influence associations between anxiety and mood disorders with psychological functioning. Each of the three psychiatric disorders was associated with greater experiential avoidance and psychological distress, and lower quality of life. Being a refugee was associated with a higher likelihood of having SAD and MDD. We found evidence for experiential avoidance as a partial mediator of the respective effects of SAD and PTSD on quality of life; experiential avoidance did not mediate the effects of disorders on global distress. We also found support for a moderation model showing that only war survivors without SAD and low experiential avoidance reported elevated quality of life; people with either SAD or excessive reliance on experiential avoidance reported compromised, low quality of life. This is the third independent study, each using a different methodology, to find empirical support for this moderation model [Kashdan, T. B., & Breen, W. E. (2008). Social anxiety and positive emotions: a prospective examination of a self-regulatory model with tendencies to suppress or express emotions as a moderating variable. Behavior Therapy, 39, 1-12; Kashdan, T. B., & Steger, M. F. (2006). Expanding the topography of social anxiety: an experience sampling assessment of positive emotions and events, and emotion suppression. Psychological Science, 17, 120-128]. Overall, we provided initial evidence for the importance of addressing PTSD, SAD, MDD, and experiential avoidance in primarily civilian war survivors.


Domestication-related changes in sexual performance of Queensland fruit fly.
In Sterile Insect Technique (SIT) programs, massive numbers of insects are reared, sterilized, and released in the field to impede reproduction of pest populations. The domestication and rearing processes used to produce insects for SIT programs may have significant evolutionary impacts on life history and reproductive biology. We assessed the effects of domestication on sexual performance of laboratory reared Queensland fruit fly, Bactrocera tryoni, by comparing an old (49 generations) and a young colony (5 generations). We evaluated mating propensity, mating latency, copula duration, sperm transfer, and ability to induce sexual inhibition in mates. Overall, both males and females from the old colony had greater mating propensity than those from the young colony. Copula duration was longer when females were from the old colony. There was no evidence of sexual isolation between the colonies as males and females from the two colonies had similar propensity to mate with flies from either colony. Males from the old colony transferred more sperm regardless of which colony their mate was from. Finally, males from both colonies were similarly able to induce sexual inhibition in their mates and were also similarly able to secure copulations with already-mated females. Positive effects of domestication on sperm transfer, coupled with maintained ability to induce sexual inhibition in mates and to secure copulations with previously mated females, highlights that domestication may have little effect, or even positive effects, on some aspects of sexual performance that may advantage mass-reared B. tryoni in SIT programs.


Verification of risk scores to predict i.v. immunoglobulin resistance in incomplete Kawasaki disease.
A recent study indicated the efficacy of the addition of prednisolone to i.v. immunoglobulin (IVIG) as initial treatment in patients with higher risk of IVIG resistance. Several different risk scores for predicting IVIG resistance have been proposed, mainly based on typical Kawasaki disease (KD) patients. We investigated the utility of the risk scores to predict IVIG resistance in incomplete KD. Clinical records of incomplete KD patients who received a single dose of IVIG between 2005 and 2012 at Kochi Health Sciences Center were retrospectively reviewed. Patients were classified into an IVIG-responsive group and an IVIG-resistant group. The Kobayashi, Egami, and Sano risk scores were calculated for each patient and the proportion of high-risk patients was compared between the two groups for each risk score. For 51 incomplete KD patients, Kobayashi (66.7% vs 47.6%, P = 0.253), Egami (55.6% vs 38.1%, P = 0.274), and Sano (57.1% vs 10.8%, P = 0.068) risk scores identified a higher proportion of high-risk patients in the IVIG-resistant group compared with the IVIG-responsive group, but significant difference was not observed. Sano risk score had the highest OR (6.19; 95%CI: 1.00-38.26). The proportion of patients identified as being at high risk for IVIG resistance using the Kobayashi, Egami, and Sano risk scores, respectively, was not significantly different between the IVIG-responsive group and the IVIG-resistant group for incomplete KD. Among the three risk scores, the Sano risk score has the best ability to predict IVIG resistance in incomplete KD.


In vitro estrogenic activities of fenugreek Trigonella foenum graecum seeds.
Trigonella foenum graecum commonly known as fenugreek, has been widely cultivated in Asia, Africa and Mediterranean countries for the edible and medicinal values of its seeds. Earlier reports show that fenugreek seeds provide a mastogenic effect resulting in enhanced breast size. However, very little is known about its estrogenic effect. The present study investigated the effect of chloroform extracts of fenugreek seeds (FCE) in breast cancer cells for its estrogenic effect, and to assess its capacity as an alternative to hormone replacement therapy (HRT). The effect of FCE on cell proliferation of estrogen receptor (ER) positive breast cancer cells, MCF-7 was studied by MTT assay at a concentration range of 20 to 320 microg/ml. The competitive ER binding assay (HAP assay) was done to find out the ER binding capacity of the extract. Transfection and reporter assay (DLR assay), and RT- PCR with an estrogen responsive gene pS2 were done to find out the transcriptional regulatory activity of FCE. FCE stimulated the proliferation of MCF-7 cells, showed binding to ER (IC(50) = 185.6 +/- 32.8 microg/ ml) and acted as an agonist for ER mediated transcription via ERE. It also induced the expression of estrogen responsive gene pS2 in MCF-7 cells. Our study provided the evidence for estrogenic activities of fenugreek seeds. Further in vitro and in vivo studies could demonstrate its suitability as an alternative to HRT.


Erosion of galilean satellite surfaces by jovian magnetosphere particles.
The Galilean satellites of Jupiter-Io (J1), Europa (J2), Ganymede (J3), and Callisto (J4)-are embedded in the intense ion and electron fluxes of the Jovian magnetosphere. The effect of these particles on the icy surfaces of the outer three satellites depends on the fluxes and the efficiency of the sputtering of water ice by such particles. Recent laboratory measurements provided data on the erosion of water ice by energetic particles and showed that it occurs much faster than would be expected from normal sputtering theory. The Voyager spacecraft encounters with Jupiter provided the first measurements of ion fluxes (energies greater, similar 30 kiloelectron volts) in the vicinity of the Galilean satellites. Using the laboratory sputtering data together with particle measurements from the Voyager 1 low-energy charged particle experiment, the effects of erosion on the surfaces of J2 to J4 are estimated. It is shown that the surface of Europa could be eroded by as much as 100 meters over an eon (10(9) years). Column densities of water vapor that could be produced around the three satellites from particle bombardment of their surfaces are also calculated, and the sources and losses of oxygen in the gravitationally bound gas produced by sputtering or sublimation are estimated.


Inhibiting phosphoglycerate dehydrogenase counteracts chemotherapeutic efficacy against MYCN-amplified neuroblastoma.
Here we sought metabolic alterations specifically associated with MYCN amplification as nodes to indirectly target the MYCN oncogene. Liquid chromatography-mass spectrometry-based proteomics identified seven proteins consistently correlated with MYCN in proteomes from 49 neuroblastoma biopsies and 13 cell lines. Among these was phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in de novo serine synthesis. MYCN associated with two regions in the PHGDH promoter, supporting transcriptional PHGDH regulation by MYCN. Pulsed stable isotope-resolved metabolomics utilizing 13 C-glucose labeling demonstrated higher de novo serine synthesis in MYCN-amplified cells compared to cells with diploid MYCN. An independence of MYCN-amplified cells from exogenous serine and glycine was demonstrated by serine and glycine starvation, which attenuated nucleotide pools and proliferation only in cells with diploid MYCN but did not diminish these endpoints in MYCN-amplified cells. Proliferation was attenuated in MYCN-amplified cells by CRISPR/Cas9-mediated PHGDH knockout or treatment with PHGDH small molecule inhibitors without affecting cell viability. PHGDH inhibitors administered as single-agent therapy to NOG mice harboring patient-derived MYCN-amplified neuroblastoma xenografts slowed tumor growth. However, combining a PHGDH inhibitor with the standard-of-care chemotherapy drug, cisplatin, revealed antagonism of chemotherapy efficacy in vivo. Emergence of chemotherapy resistance was confirmed in the genetic PHGDH knockout model in vitro. Altogether, PHGDH knockout or inhibition by small molecules consistently slows proliferation, but stops short of killing the cells, which then establish resistance to classical chemotherapy. Although PHGDH inhibition with small molecules has produced encouraging results in other preclinical cancer models, this approach has limited attractiveness for patients with neuroblastoma.


Gender-Related Differences in Heart Rate Variability of Epileptic Patients.
Recently, heart rate variability (HRV) analysis has been used as an indicator of epileptic seizures. As women have a lower sudden, unexpected death in epilepsy risk and greater longevity than men, the authors postulated that there are significant gender-related differences in heart rate dynamics of epileptic patients. The authors analyzed HRV during 5-minute segments of continuous electrocardiogram recording of age-matched populations. The middle-aged epileptic patients included males ( n = 12) and females ( n = 12), ranging from 41 to 65 years of age. Relatively high- (0.15 Hz-0.40 Hz) and low-frequency (0.01 Hz-0.15 Hz) components of HRV were computed using spectral analysis. Poincaré parameters of each heart rate time series were considered as nonlinear features. The mean heart rate markedly differed between gender groups including both right- and left-sided seizures. High-frequency heart rate power and the low-frequency/high-frequency ratio increased in the pre-ictal phase of both male and female groups ( p < .01), but men showed more increase especially in right-sided seizures. The standard deviation ratio, SD2/ SD1, of pre-ictal phase was greater in males than females ( p < .01). High-frequency spectral power and parasympathetic activity were higher in the female group with both right- and left-sided seizures. Men showed a sudden increase in sympathetic activity in the pre-ictal phase, which might increase the risk of cardiovascular disease in comparison to women. These complementary findings indicate the need to account for gender, as well as localization in HRV analysis.


Epidemiology of tattoo skin disease in bottlenose dolphins Tursiops truncatus from the Sado estuary, Portugal.
We report on the epidemiology of tattoo disease in a community of bottlenose dolphins Tursiops truncatus from the Sado estuary, Portugal. The presence of tattoos (T++) and tattoo-like (T+) lesions was examined in 586 photographic records of 35 dolphins taken from 1994 to 1997. Images were rated into 3 categories: good (GI), average (AI) and poor (PI). Dolphins positive for T++ lesions were observed in 19 GI. Dolphins with T+ lesions were seen in 39 GI, 23 AI and 6 PI. For statistical analysis the dolphins were divided into 2 age classes (immature and adult) and the data grouped into 2 periods (1994-1995 and 1996-1997). Minimum prevalence of T++ lesions in 32 dolphins was 21.9% in 1994-1995 and 15.6% in 1996-1997. Variation in prevalence of tattoo disease between the 2 age classes was examined for each period, excluding animals with T+ lesions or considering them either positive or negative for tattoos. Prevalence of the disease was significantly higher in immature dolphins than in adults during both periods, except in the first one when T+ lesions were considered as true tattoos. Temporal variation in prevalence of tattoo disease was examined in 23 adults. Prevalence was significantly higher in 1994-1995 (39.1%) than in 1996-1997 (17.4%). Differences in the number and quality of pictures did not cause significant biases that could have favoured the detection of lesions between age classes or periods. Minimal persistence of the disease ranged between 3 and 45.5 mo. The lesions converted into light grey marks when healing, but may recur. The presence of very large lesions in 2 adult dolphins affected for years may be related to the contamination of the estuary. The high prevalence of the disease, its long persistence, as well as higher frequency in immature individuals, suggest that it is endemic in bottlenose dolphins from the Sado estuary. The contribution of tattoo disease to the decline of this community should be investigated. Three of the 5 dolphins that died during this study had T++ and T+ lesions.


Physical activity-related well-being in older adults: social cognitive influences.
In this study, the pattern and correlates of physical activity-related well-being in older adults (N = 174; men = 49, women = 125; mean age = 66 years) were examined across a 6-month exercise trial. Baseline levels of self-efficacy fitness, importance of physical activity, and social support and exercise participation across the trial were used as correlates of positive and negative feeling states. Psychological responses to physical activity were assessed on a bimonthly basis across the trial. Latent growth curve analyses indicated significant growth in positive well-being over the 6-month period, with increases reaching a threshold at 4 months. Self-efficacy was inversely related to change in positive well-being across the trial. Frequency of activity and increases in well-being over the trial were significant predictors of self-efficacy at program termination. Findings suggest the social cognitive context of the exercise experience may have influence on exercise-related well-being.


Applying outdoor environment to develop health, comfort, and energy saving in the office in hot-humid climate.
A human life demand set to emerge in the future is the achievement of sustainability by maintaining a comfortable indoor environment without excessive reliance on energy-consuming air conditioners. The major research processes in this study are: (1) measuring indoor air quality and thermal comfort to evaluate the comfort of an indoor environment; (2) implementing questionnaire survey analysis to explore people's environmental self-perceptions and conducting a meta-analysis of the measurement results for air quality and physical aspects; and (3) constructing an indoor monitoring and management system. The experimental and analysis results of this research reveal that most of the office occupants preferred a cooler environment with a lower temperature. Additionally, because the summers in Taiwan are humid and hot, the occupants of an indoor space tend to feel uncomfortable because of the high humidity and poor indoor air quality. Therefore, Variable Air Volume (VAV), two air intakes, and exhaust plant are installed to improve indoor environment. After improvement, a lower temperature (approximately 21.2-23.9°C) indirectly reduces humidity, thereby making the occupants comfortable. Increasing air velocity to 0.1~0.15 m/s, the carbon dioxide concentrations decrease below the requirement of the WHO. Ninety-five percent of the workers corresponded to the standard comfort zone after this improvement.


Baseline Characteristics of Patients With Cavernous Angiomas With Symptomatic Hemorrhage in Multisite Trial Readiness Project.
Brain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel magnetic resonance imaging biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH. This prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six US sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale and National Institutes of Health Stroke Scale), and patient quality of life outcomes (Patient-Reported Outcomes Measurement Information System-29 and EuroQol-5D) were summarized using descriptive statistics. Patient-Reported Outcomes Measurement Information System-29 scores were standardized against a reference population (mean 50, SD 10), and one-sample t test was performed for each domain. A subgroup underwent harmonized magnetic resonance imaging assessment of lesional iron content with quantitative susceptibility mapping and vascular permeability with dynamic contrast-enhanced quantitative perfusion. As of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (modified Rankin Scale score ≤2 and National Institutes of Health Stroke Scale score <5). However, perceived health problems affecting quality of life were reported in >30% of patients (EuroQol-5D). Patients had significantly worse Patient-Reported Outcomes Measurement Information System-29 scores for anxiety (P=0.007), but better depression (P=0.002) and social satisfaction scores (P=0.012) compared with the general reference population. Mean baseline quantitative susceptibility mapping and permeability of CASH lesion were 0.45±0.17 ppm and 0.39±0.31 mL/100 g per minute, respectively, which were similar to historical CASH cases and consistent across sites. These baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH.


Non-adrenergic, non-cholinergic contractions in the electrically field stimulated guinea-pig trachea.
1. The effects of drugs and altering stimulus parameters on neurogenic responses to electrical field stimulation (EFS) have been investigated in distal and proximal portions of the guinea-pig trachea. 2. In the presence of indomethacin (3 microM) and propranolol (1 microM) two contractile phases were evident in both the proximal and distal trachea. The first rapid phase was abolished by atropine (0.1 microM), whereas the prolonged, second phase was abolished by capsaicin (10 microM) pretreatment. Tetrodotoxin (3 microM) abolished the initial response and greatly inhibited the second phase. In proximal trachea this second phase was evident only in 9 of 22 preparations. The addition of the peptidase inhibitor thiorphan (10 microM) however, caused a second phase to be seen in all the proximal tissues examined. 3. The two phases of the contractions to EFS were differentially sensitive to the pulse duration applied. The initial, cholinergic contractions were evident at lower pulse durations than were the prolonged capsaicin-sensitive contractions, with the first phase being approximately 10 fold more sensitive than the second phase. 4. The magnitude of the capsaicin-sensitive contraction to EFS was significantly greater in the distal trachea than in the proximal trachea. This difference prevailed in the presence of thiorphan, an inhibitor of neutral endopeptidase. In contrast, concentration-response curves to capsaicin were similar in segments of proximal and distal trachea. 5. The non-adrenergic non-cholinergic (NANC) relaxant responses were studied in tissues in which excitatory neurogenic responses were pharmacologically abolished by capsaicin and atropine treatment. The NANC relaxant responses in the proximal trachea were evident at lower pulse frequencies and were of greater magnitude compared with NANC relaxant responses in the distal trachea. 6. These results indicate that, by pharmacologically manipulating the trachea and by selecting optimum stimulation parameters, a NANC contractile response to EFS can be seen throughout the length of the guinea-pig trachea. This NANC response is most likely to be due to the release of tachykinins from capsaicin-sensitive sensory fibres. It is suggested that NANC relaxant responses mask NANC contractile responses especially in the proximal trachea where NANC relaxant responses predominate.


[Morphological and histological comparison of the digestive tract of Gambusia puncticulata and Girardinus metallicus, fishes used in the biological control of mosquitoes].
The morphology and histology of the digestive tract of Gambusia puncticulata and Girardinus metallicus fishes used in the biological control of mosquito larvae in Cuba, were described and compared. They were related to the food habits of each species. Gambusia puncticulata has a short and thick intestine, which is characteristic of the carnivorous species, whereas Girardinus metallicus has an elongate and thin spiral rolled up intestine as it corresponds to the omnivorous fishes. It was observed that the histological pattern of the intestine in both species is very simple; however, Gambusia puncticulata presented a great number of ramified microhairiness on comparing it with Girardinus metallicus, which increases this way the digestive yield of its relatively shorter digestive tract.


In-utero Diagnosis of Prostatic Embryonal Rhabdomyosarcoma.
Though rhabdomyosarcoma is the most common soft-tissue tumor diagnosed in children there are no reported cases of prenatally detected prostatic embryonal rhabdomyosarcoma. This report demonstrates the first reported case of this phenomenon and its subsequent workup, diagnosis, and treatment.


[Diagnosis of aortic valve calcinosis with a view to the surgical treatment of aortic valve disease].
Combined roentgenologic/echocardiographic diagnosis of aortic valve calcinosis was made in 135 patients operated on for a rheumatic aortic heart disease. Four degrees of aortic valve calcinosis were identified: 1) isolated fine points of calcinosis, as revealed by echolocation and specific treatment of the removed valves; 2) small-focal calcinosis as revealed roentgenologically in 79.2% of cases and by echolocation, in 93%; 3) large-focal, and 4) wide-spread calcinosis, the latter two being detectable both roentgenologically and echocardiographically in all cases. The 4-degree classification of aortic valvular lesions allows a detailed assessment of the nature of the affection that is important for the choice of surgical procedure.


Detection of the arcuate fasciculus in congenital amusia depends on the tractography algorithm.
The advent of diffusion magnetic resonance imaging (MRI) allows researchers to virtually dissect white matter fiber pathways in the brain in vivo. This, for example, allows us to characterize and quantify how fiber tracts differ across populations in health and disease, and change as a function of training. Based on diffusion MRI, prior literature reports the absence of the arcuate fasciculus (AF) in some control individuals and as well in those with congenital amusia. The complete absence of such a major anatomical tract is surprising given the subtle impairments that characterize amusia. Thus, we hypothesize that failure to detect the AF in this population may relate to the tracking algorithm used, and is not necessarily reflective of their phenotype. Diffusion data in control and amusic individuals were analyzed using three different tracking algorithms: deterministic and probabilistic, the latter either modeling two or one fiber populations. Across the three algorithms, we replicate prior findings of a left greater than right AF volume, but do not find group differences or an interaction. We detect the AF in all individuals using the probabilistic 2-fiber model, however, tracking failed in some control and amusic individuals when deterministic tractography was applied. These findings show that the ability to detect the AF in our sample is dependent on the type of tractography algorithm. This raises the question of whether failure to detect the AF in prior studies may be unrelated to the underlying anatomy or phenotype.


The effect of transformer, doublesex and intersex mutations on the sexual behavior of Drosophila melanogaster.
We have identified the effects of genes that regulate sex determination on female-specific tissues in the abdomen that produce sex pheromones and parts of the central nervous system that function when a male performs courtship. To do this, we monitored the sexual behaviors of flies with mutations in the transformer (tra), doublesex (dsx) and intersex (ix) genes. Except for tra, which transforms diplo-X flies so that they look and function like normal males, these mutations do not have the same effect on pheromone-producing tissues and the central nervous system as they do on the appearance of the fly. The dsx and ix mutations, which make diplo-X-flies look like intersexes, do not transform the flies so that they can perform courtship, suggesting that these genes do not regulate the development of sex-specific parts of the central nervous system. Conversely, the ix mutation, which has no effect on the appearance of haplo-X flies, makes the flies sexually attractive and impairs their ability to perform courtship, which implies that the ix gene is active in internal tissues of males.


[Laparascopic surgical treatment of non-parasitic hepatic cyst].
The experience with seven cases of non-parasitic liver cyst, seen in a seven year period, (between 1992 to 1998) at the "Hospital Español" of Veracruz is presented. Clinical symptoms and signs are described, being the main one upper abdominal pain due to the size of the cyst and the compression over different organs. The diagnosis was made by images obtained from ultrasound and CT scan. The cyst average size was 14 cm, and in 28.57% of them, other small cysts were found. The surgical treatment included resection of the superficial capsule of the cyst and the electrocoagulation of the residual inner capsule. The procedure was performed using laparoscopic techniques. There were no surgical incidents, neither post-operatory complications or mortality. The clinical evolution of all patients was successful. We found some evidence from the international literature about the laparoscopic techniques in these patients. Our results were similar to other reports. There are no previous reports in the Mexican literature about this surgical technique in the management of the non-parasitic liver cyst disease.


Laser micromachining of periodic surface radius change on the optical fiber circumference.
In this paper, we are showing that holes and marking spots with sizes that are comparable to the wavelength of a CO2 laser at λ=10.6 μm can be achieved reproducibly on a conventional optical fiber SMF28 when it is positioned at the focal point. Some theory on Gaussian beam propagation is briefly reviewed and readily applied to drill a fiber on its axis near the focal point. As the fiber was moved from the focal point, it was found that some features, such as ridges along the fiber circumference, were also micromachined by the laser. It was demonstrated that the fabrication of surface nanoaxial photonic fibers, long-pitch grating fibers, and pump laser strippers can be envisaged on a conventional SMF28 with a cladding diameter of 125 μm.


Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes.
Obestatin is a 23-amino acid C-terminally amidated gastrointestinal peptide derived from preproghrelin and which forms an α helix. Although obestatin has a short biological half-life and is rapidly degraded, it is proposed to exert wide-ranging pathophysiological actions. Whilst the precise nature of many of its effects is unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. For example, obestatin has been reported to inhibit food and water intake, body weight gain and gastrointestinal motility and also to mediate promotion of cell survival and prevention of apoptosis. Obestatin-induced increases in beta cell mass, enhanced adipogenesis and improved lipid metabolism have been noted along with up-regulation of genes associated with beta cell regeneration, insulin production and adipogenesis. Furthermore, human circulating obestatin levels generally demonstrate an inverse association with obesity and diabetes, whilst the peptide has been shown to confer protective metabolic effects in experimental diabetes, suggesting that it may hold therapeutic potential in this setting. Obestatin also appears to be involved in blood pressure regulation and to exert beneficial effects on endothelial function, with experimental studies indicating that it may also promote cardioprotective actions against, for example, ischaemia-reperfusion injury. This review will present a critical appraisal of the expanding obestatin research area and discuss the emerging therapeutic potential of this peptide for both metabolic and cardiovascular complications of diabetes.


Fetal alcohol syndrome and its long-term effects.
Ancient scripture and paintings together with several medical reports on the effect of alcohol on the newborn over the past 300 years finally led to the description of the fetal alcohol syndrome in the 1970s by French and American research groups. Maternal alcohol abuse during pregnancy can result in the specific pattern of malformations and neurocognitive deficits characteristic of this syndrome. Diagnostic criteria and classifications have been developed and in the 1990s reports showed the long-term consequences for these children. In recent years several studies from different countries have shown that prenatal alcohol exposure will lead to life-long consequences on physical development, intellectual development, behavior, social development, occupation, independence, sexuality or sexual behavior and increased risk of suicidality. In this review of long-term observation studies we found that the prenatal exposure to alcohol have permanent and life-long damage, which impair both the social and occupational future of the person exposed with a need for life-long assistance in order for that person to function at an optimal level. Primary prevention and early intervention with general public health educational efforts seems to be the best way forward.


Capturing lessons learned from evidence-to-policy initiatives through structured reflection.
Knowledge translation platforms (KTPs), which are partnerships between policymakers, stakeholders, and researchers, are being established in low- and middle-income countries (LMICs) to enhance evidence-informed health policymaking (EIHP). This study aims to gain a better understanding of the i) activities conducted by KTPs, ii) the way in which KTP leaders, policymakers, and stakeholders perceive these activities and their outputs, iii) facilitators that support KTP work and challenges, and the lessons learned for overcoming such challenges, and iv) factors that can help to ensure the sustainability of KTPs. This paper triangulated qualitative data from: i) 17 semi-structured interviews with 47 key informants including KTP leaders, policymakers, and stakeholders from 10 KTPs; ii) document reviews, and iii) observation of deliberations at the International Forum on EIHP in LMICs held in Addis Ababa in August 2012. Purposive sampling was used and data were analyzed using thematic analysis. Deliberative dialogues informed by evidence briefs were identified as the most commendable tools by interviewees for enhancing EIHP. KTPs reported that they have contributed to increased awareness of the importance of EIHP and strengthened relationships among policymakers, stakeholders, and researchers. Support from policymakers and international funders facilitated KTP activities, while the lack of skilled human resources to conduct EIHP activities impeded KTPs. Ensuring the sustainability of EIHP initiatives after the end of funding was a major challenge for KTPs. KTPs reported that institutionalization within the government has helped to retain human resources and secure funding, whereas KTPs hosted by universities highlighted the advantage of autonomy from political interests. The establishment of KTPs is a promising development in supporting EIHP. Real-time lesson drawing from the experiences of KTPs can support improvements in the functioning of KTPs in the short term, while making the case for sustaining their work in the long term. Lessons learned can help to promote similar EIHP initiatives in other countries.


Iron and citrate export by a major facilitator superfamily pump regulates metabolism and stress resistance in Salmonella Typhimurium.
The efficacy of antibiotics and host defenses has been linked to the metabolic and redox states of bacteria. In this study we report that a stress-induced export pump belonging to the major facilitator superfamily effluxes citrate and iron from the enteric pathogen Salmonella Typhimurium to arrest growth and ameliorate the effects of antibiotics, hydrogen peroxide, and nitric oxide. The transporter, formerly known as MdtD, is now designated IceT (iron citrate efflux transporter). Iron efflux via an iron-chelating tricarboxylic acid cycle intermediate provides a direct link between aerobic metabolism and bacterial stress responses, representing a unique mechanism of resistance to host defenses and antimicrobial agents of diverse classes.


Genetic resistance to Brucella abortus in the water buffalo (Bubalus bubalis).
Brucellosis is a costly disease of water buffaloes (Bubalus bubalis). Latent infections and prolonged incubation of the pathogen limit the efficacy of programs based on the eradication of infected animals. We exploited genetic selection for disease resistance as an approach to the control of water buffalo brucellosis. We tested 231 water buffalo cows for the presence of anti-Brucella abortus antibodies (by the agglutination and complement fixation tests) and the Nramp1 genotype (by PCR-denaturing gradient gel electrophoresis). When the 231 animals (58 cases and 173 controls) were divided into infected (seropositive) and noninfected (seronegative) groups and the Nramp1 genotypes were compared, the seropositive subjects were 52 out of 167 (31%) in the Nramp1A+ (Nramp1AA or Nramp1AB) group and 6 out of 64 (9.4%) in the Nramp1A- (Nramp1BB) group (odds ratio, 4.37; 95% confidence limits, 1.87 to 10.19; chi2, 11.65 for 1 degree of freedom). Monocytes from Nramp1BB subjects displayed significantly (P < 0.01) higher levels of Nramp1 mRNA than Nramp1AA subjects and also a significantly (P < 0.01) higher ability in controlling the intracellular replication of several Brucella species in vitro. Thus, selection for the Nramp1BB genotype can become a valuable tool for the control of water buffalo brucellosis in the areas where the disease is endemic.


Glutathione-triggered "off-on" release of anticancer drugs from dendrimer-encapsulated gold nanoparticles.
Polymeric nanoparticles that can stably load anticancer drugs and release them in response to a specific trigger such as glutathione are of great interest in cancer therapy. In the present study, dendrimer-encapsulated gold nanoparticles (DEGNPs) were synthesized and used as carriers of thiolated anticancer drugs. Thiol-containing drugs such as captopril and 6-mercaptopurine loaded within DEGNPs showed an "Off-On" release behavior in the presence of thiol-reducing agents such as glutathione and dithiothreitol. Thiolated doxorubicin and cisplatin, loaded within the nanoparticle, showed much reduced cytotoxicity as compared to the free anticancer compounds. The toxicity of drug-loaded DEGNPs can be enhanced by improving the intracellular glutathione. Glutathione-triggered release of thiolated doxorubicin within cancer cells is further confirmed by flow cytometry and confocal laser scan microscopy studies. In addition, DEGNPs showed excellent biocompatibility on several cell lines. This study provides a new insight into biomedical applications of dendrimers and dendrimer-encapsulated nanoparticles.


Comparative connective tissue structure-function relationships in biologic pumps.
A complex connective tissue framework exists in mammalian hearts that surrounds and interconnects individual myocytes and fascicles of cells. Recent evidence suggests that this connective tissue plays a role in maintaining shape, modulating contractile forces, and mediating elastic recoil during cavity filling and contraction. In order to analyze the involvement of connective tissue in pump contraction and recoil, we examined silver impregnated connective tissue in rat hearts which spontaneously jet through fluid ex vivo by contracting their cavities forcefully and then sucking fluid for the next cycle, and compared them to frog hearts which beat actively under the same conditions, but do not demonstrate jet propulsion. A further analysis was carried out in unrelated but analogous models: the squid and octopus. The former jets rapidly through the ocean, while the latter moves sinuously along the seabed. We observed highly interconnected myocytes in the rat heart, whereas frog myocytes are individually wrapped by connective tissue but are not interconnected. The squid mantle muscle is surrounded by a complex connective tissue grid that is tethered to each muscle cell, whereas the octopus mantle muscle cells are surrounded by connective tissue but are not tethered. These observations suggest that myocyte connective tissue tethering may be necessary for muscle cavities to generate forceful and coordinated contractions sufficient for rapid ejection and suction of fluid.


Treatment of unilateral crossbite using modified palatal arch: case report.
Severe unilateral crossbite was diagnosed in a five-year and five-month Taiwanese girl. Clinical examination presented left posterior and anterior crossbites resulting in significant dental and facial midline deviations. Early intervention was recommended in this case for severe functional shift which might induce facial asymmetry. The unilateral crossbite was successfully treated using modified palatal arch with finger springs. The patient has shown stable occlusion and no midline deviation after six years of follow-up.


Melatonin and colon carcinogenesis. III. Effect of melatonin on proliferative activity and apoptosis in colon mucosa and colon tumors induced by 1,2-dimethylhydrazine in rats.
Forty-eight two-month-old outbred female LIO rats were injected weekly with a single dose of 1,2-dimethylhydrazine (DMH; 21 mg/kg of body weight) administered s.c. for 15 consecutive weeks. From the day of the 1st injection of the carcinogen the part of rats were given five days a week during the night time (from 18.00 h to 08.00 h) melatonin dissolved in tap water, 20 mg/l. 10 rats were treated similarly with solvents and served as control. The experiment was terminated 6 months after the first injection of the carcinogen. Colon tumors (mainly adenocarcinomas) developed in a hundred percent of rats exposed both to DMH or to DMH plus melatonin. However, descending colon carcinomas were observed in 65 % of rats exposed to DMH plus melatonin against 100% in those exposed to DMH alone (p < 0.01). The multiplicity of colon tumors was also reduced in rats under the influence of melatonin. This effect is correlated with the significant inhibitory effect of the pineal hormone on mitotic index and with stimulating effect of melatonin on the relative number of apoptotic cells (TUNEL-method) in colon tumors. Long-term treatment with melatonin was followed also by the decrease in the area of lymphoid infiltrates in the colon mucosa of tumor-bearing rats.


Correlation of spontaneous and traumatic anterior skull base CSF leak flow rates with fluid pattern on early, delayed, and subtraction volumetric extended echo train T2-weighted MRI.
CSF leakage is a potentially fatal condition that may result when a skull base dural defect permits CSF communication between the cranial vault and sinonasal cavities. Flow rate is an important property of CSF leaks that can contribute to surgical decision-making and predispose patients to complications and inferior outcomes. Noninvasive preoperative prediction of the leak rate is challenging with traditional diagnostic tools. The present study compares fluid configurations on early and late volumetric extended echo train T2-weighted MRI by using image tracings and sequence subtraction as a novel method of quantifying CSF flow rate, and it correlates radiological results with intraoperative findings and clinical outcomes. A total of 45 patients met inclusion criteria for this study and underwent 3-T MRI. Imaging sequences included two identical CUBE T2 (vendor trade name for volumetric extended echo train T2) acquisitions at the beginning and end of the scanning session, approximately 45 minutes apart. Twenty-five patients were confirmed to have definitive spontaneous or traumatic anterior skull base CSF leaks. Semiautomated volumetric segmentation of CSF intensity was performed on both CUBE data sets by using 3D-Slicer software, and volumes were subtracted to obtain accumulated CSF volume. These imaging-derived fluid accumulations were correlated with high- or low-flow states, as well as ultimate treatment outcomes including recurrences. Of the 45 patients, 25 (55.6%) had definitive evidence of CSF leakage, and 22 (88%) of these underwent surgical repair. Patients with high-flow CSF leaks had higher early (4.058 cm3 vs 0.982 cm3, p = 0.04), late (4.58 cm3 vs 1.096 cm3, p = 0.04), and accumulated (0.53 cm3 vs 0.11 cm3, p = 0.01) fluid volume measurements than patients with low-flow leaks. The 5 (22.7%) patients who exhibited postoperative CSF leak recurrence had significantly greater early (6.30 cm3 vs 1.23 cm3, p = 0.008) and late (6.87 cm3 vs 1.45 cm3, p = 0.008) volumes. Accumulated volume was not significantly greater in patients with leak recurrence (0.58 cm3 vs 0.22 cm3, p = 0.07). Early, late, and accumulated volumes were significantly correlated with postoperative hospital stay as well as duration of postoperative lumbar drain placement (p < 0.05 for all measures). High-resolution CUBE T2 MRI, coupled with precise volumetric segmentation and subtraction of sinonasal hyperintensity, not only demonstrated predictive value in differentiating low- and high-flow CSF leaks, but also correlated with postoperative complications such as leak recurrence. These findings may be useful in the clinical workup and neurosurgical management of patients with skull base CSF leaks.


A Retrospective Study of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer.
To explore the efficacy and safety of neoadjuvant chemotherapy in the doublet and triplet regimens of locally advanced gastric cancer. A retrospective analysis was conducted on 162 patients with gastric cancer who received neoadjuvant chemotherapy, including 74 patients receiving doublet regimen (fluorouracil/platinum) and 88 patients receiving triplet regimen (fluorouracil/platinum/Taxol). Patients in both groups received neoadjuvant chemotherapy for two cycles, and underwent surgical resection 4 weeks after the end of chemotherapy. The total clinical remission rate was 68.6% (105/153), the phase-down rate was 46.4% (71/153), and the pathological response rate was 59.9% (97/162). In the doublet and triplet regimen, the clinical remission rate was 65.7% (44/67) and 70.9% (61/86) (P = 0.708), the descending period rate was 41.8% (28/67) and 50.0% (43/86) (P = 0.485), and the pathological response rate was 51.4% (38/74) and 67.0% (59/88) (P = 0.190). The median disease-free survival (DFS) and overall survival (OS) of 162 patients were 36.0 and 58.5 months. In the doublet and triplet regimen, the median DFS was 38.0 and 34.0 months (P = 0.377), and the median OS was 59.0 and 56.5 months (P = 0.256). The side effects of the doublet group were significantly lower than those of the triplet group, with leucopenia rate of 45.9% (34/74) and 62.5% (55/88) (P = 0.035); thrombocytopenia rate of 18.9% (14/74) and 35.2% (31/88) (P = 0.021); nausea rate of 45.9% (34/74) and 64.8% (57/88) (P = 0.016), and diarrhea rate of 1.4% (1/74) and 9.1% (8/88) (P = 0.032). Neoadjuvant chemotherapy is safe and effective for locally advanced gastric cancer. The clinical efficacy of neoadjuvant chemotherapy in the doublet group and the triplet group is equivalent, and the doublet group has better safety and tolerance.


Progression independent of relapses in aquaporin4-IgG-seropositive neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, and multiple sclerosis.
To determine whether progression independent of relapse activity (PIRA) is present in Aquaporin4-IgG-seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD), Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and relapsing remitting Multiple sclerosis (RRMS). We retrospectively studied the change in EDSS, confirmed disability worsening (CDW) (i.e., PIRA), and new MRI lesions in AQP4+NMOSD, and MOGAD and MS patients. Linear mixed-effect regression model was used to compare the longitudinal changes in EDSS, and Cox regression was used to compare changes in MRI. The estimated mean ΔEDSS in the AQP4+NMOSD and matched MS group were +0.06 (95%CI: -0.40, +0.52, p = 0.76), and +0.02 (95%CI: -0.05, +0.08, p = 0.6) respectively. The same estimate was -0.08 (95%CI: -0.18, +0.02, p = 0.12) in MOGAD and +0.05 (95%CI: -0.05, +0.15, p = 0.35) in matched MS group. Comparing groups for the presence of CDW (i.e., PIRA) showed that PIRA is more associated with MS compared to AQP4+NMOSD (p = 0.02) and MOGAD (p<0.001). Compared to their matched MS groups, the annualized rate of PIRA was significantly lower in AQP4 (0.08 vs 0.44; p<0.0001), and MOG groups (0.04 vs 0.13; p<0.0001). New T2 or enhancing lesions on brain MRI were higher in MS compared to AQP4+NMOSD and MOGAD patients. Relapse-independent changes in the EDSS, CDW, and MRI activity are not common in AQP4+NMOSD and MOGAD, especially when compared with MS. Since our patients were on relapse prevention therapies at the time of EDSS measurements, our study supports the importance of preventing relapses in AQP4+NMOSD and MOGAD and suggests different pathologic mechanisms of relapse-free neurological damage between MS and AQP4+NMOSD/MOGAD.


Urate uptake in membrane vesicles of rat renal cortex: effect of copper.
[2-14C]Urate uptake was studied in brush border and basolateral membrane vesicles of rat renal cortex. In the absence of copper, urate equilibrated without metabolism of transported urate. Exposure of the vesicles to copper significantly stimulated uptake, and in these vesicles uptake was also stimulated by NaCl or KCl gradients. Allantoin accumulated in these vesicles due to oxidation of transported urate. This oxidation is ascribed to a copper-stimulated, membrane-associated uricase since purified uricase and the membranes had similar Km values, both were inhibited by oxonic acid, and extramembranal uricase was not detected. Oxonic acid and pyrazinoic acid inhibited both uptake and enzyme activity. These findings suggest that urate uptake is carrier mediated and that uricase may play some role in transport. In addition, it appears that a significant loss of copper occurs during isolation of membrane vesicles that profoundly affects the characteristics of urate uptake. Those properties of the membrane that influence urate uptake, however, can be restored by exposure of the membranes to copper.


Colocalization of dihydropyridine and ryanodine receptors in neonate rabbit heart using confocal microscopy.
Because of undeveloped T tubules and sparse sarcoplasmic reticulum, Ca(2+)-induced Ca(2+) release (CICR) may not be the major mechanism providing contractile Ca(2+) in the neonatal heart. Spatial association of dihydropyridine receptors (DHPRs) and ryanodine receptors (RyRs), a key factor for CICR, was examined in isolated neonatal rabbit ventricular myocytes aged 3-20 days by double-labeling immunofluorescence and confocal microscopy. We found a significant increase (P < 0.0005) in the degree of colocalization of DHPR and RyR during development. The number of voxels containing DHPR that also contained RyR in the 3-day-old group (62 +/- 1.8%) was significantly lower than in the other age groups (76 +/- 1.3 in 6-day old, 75 +/- 1.2 in 10-day old, and 79 +/- 0.9% in 20-day old). The number of voxels containing RyR that also contained DHPR was significantly higher in the 20-day-old group (17 +/- 0.5%) compared with the other age groups (10 +/- 0.7 in 3-day old, 11 +/- 0.6 in 6-day old, and 11 +/- 0.5% in 10-day old). During this period, the pattern of colocalization changed from mostly peripheral to mostly internal couplings. Our results provide a structural basis for the diminished prominence of CICR in neonatal heart.


[Diagnosis and therapy of Parkinson's disease].
The clinical diagnosis of Parkinson's disease is mainly based upon the principal symptoms bradykinesia, rigidity and tremor at rest. The differential diagnosis of idiopathic Parkinson's disease (IPD) from other parkinsonisms is from the prognostic and therapeutic standpoint of considerable importance because the Parkinson-Plus syndrome generally does not or only poorly responds to a dopaminergic therapy. The treatment of IPD comprises, in addition to, dopaminergic medications such as L-dopa or dopamine receptor agonists, operative therapeutic options such as deep brain stimulation and nondrug therapies.


Teachers' attitudes and beliefs about homosexuality.
Schools play a key role in transmitting attitudes towards sexual diversity. Many studies stress the importance of teachers' and other professionals' attitudes towards gay men and/or lesbian women. This study evaluates attitudes and prejudices toward homosexuality in a sample of 254 elementary and high school teachers in Barcelona and its surrounding area. The results obtained using a scale of overt and subtle prejudice and a scale of perceived discrepancy of values indicate that discrepancy between likely behavior and personal values was significantly greater in women, those who hold religious beliefs, churchgoers and people without any gay or lesbian acquaintances. Approximately 88% of the teachers showed no type of prejudiced attitudes towards gay men and lesbian women. The experience of proximity to gay men and/or lesbian women reduces not only the discrepancy between personal values and likely behavior but also the presence of homophobic prejudice. It would be advisable to expand specific teacher training in the subject of sexual diversity in order to reduce prejudicial attitudes, thus fostering non-stereotyped knowledge of homosexuality.


Is the COVID-19 epidemic affecting the body mass of Chinese teenagers? - A longitudinal follow-up study.
After the spread and outbreak of COVID-19 worldwide, the learning, lifestyle, and health level of young individuals have been immensely impacted. With regard to the existing studies, the development trend of adolescents' body shape in the late COVID-19 period is not sufficiently analyzed, and relevant targeted investigation is lacking. This study aimed to explore the body mass index (BMI) changes of 6-14 years-old adolescents before and after the COVID-19 epidemic, and to provide a reference for promoting the continuous enhancement of adolescent health. The BMI and related data pertaining to 93,046 individuals from 2019 to 2022 were collected by cluster sampling, and changes in the BMI Z score and detection rate of overweight and obese adolescents before and after the epidemic were analyzed. Furthermore, the trend of obesity rates among adolescents in Jinan from 2019 to 2022 was analyzed using a logistic regression analysis model. The one-way ANOVA models indicated that the BMI Z score of 6-14 years-old adolescents in 2020 significantly increased compared to 2019 (p < 0.01), and decreased in 2021 and 2022; in 2020, the obesity rate of adolescents exhibited a significant increase; however, the rate decreased after being controlled in 2021 and 2022. The normal-body size proportion continued to rise (p < 0.01), and adolescents of different age groups and genders exhibited similar development trends; the results of the logistic regression analysis indicate that there was a significant increase in obesity rates in 2020, adolescents of different age groups and genders exhibited similar development trends (p < 0.05). This study demonstrated that the COVID-19 epidemic impacts the BMI and obesity detection rate of adolescents. Adolescents from different age groups and genders exhibited similar development trends.


Breast cancer screening in 21 countries: delivery of services, notification of results and outcomes ascertainment.
Following clinical trial evidence of mammography screening's efficacy and effectiveness, data are needed from organized population-based programmes to determine whether screening in these programmes results in breast cancer mortality reductions comparable to those demonstrated in controlled settings. The International Breast Cancer Screening Network (IBSN) conducted two international programme assessments: in 1990 among nine countries and in 1995 among 22 countries, obtaining information on the organization and process for screening within breast cancer screening programmes. This manuscript describes procedures for recruitment, service delivery, interpretation and communication of results, case ascertainment, and quality assurance. Practices in more established programmes are compared with pilot programmes. Each IBSN country defined a unique programme of population-based breast cancer screening. Some programmes were sub-national rather than national in scope, while others were in pilot stages of development. Screening took place in dedicated centres in established programmes and in both dedicated and general radiology centres in pilot programmes. Although most countries used personal invitation systems to recruit women to screening, other recruitment mechanisms were used. Most countries used two-view mammography in their screening programmes. About half had implemented independent double reading of mammograms, considering it a key component of high-quality mammography screening. In conclusion, diversity exists in the organization and delivery of screening mammography internationally. Quality assurance activities are a priority and are being evaluated in the IBSN.


Cimetidine for recurrent ulcer after vagotomy or gastrectomy: a randomised controlled trial.
In a randomised controlled trial cimetidine 1 g daily for six weeks was compared with placebo in the treatment of recurrent ulcers after gastrectomy or vagotomy for duodenal ulcer. Healing, assessed endoscopically, was seen in seven out of 12 patients given cimetidine and in five out of 12 controls. Four of the controls whose ulcers did not heal were subsequently treated with cimetidine, and in two the ulcers healed after six weeks. Pain recorded by the patient and consumption of alkalis were each slightly but not significantly less in the cimetidine-treated patients. When cimetidine is to be used for recurrent ulceration probably the dosage and duration of treatment should be increased.


Opioid antagonist-induced modulation of cerebral and hippocampal development: histological and morphometric studies.
The role of endogenous opioid systems in preweaning cerebral and hippocampal development was explored in rats utilizing naltrexone, a potent opioid antagonist. Sprague-Dawley rats were given daily injections (s.c.) of either 1 or 50 mg/kg naltrexone to invoke a temporary or complete blockade, respectively, of opioid receptors throughout the first 3 weeks of postnatal life; animals injected with sterile water served as controls. At weaning (Day 21), macroscopic, morphometric, and histological assessments were undertaken. In general, 50 mg/kg naltrexone had a stimulatory action on brain development, whereas 1 mg/kg naltrexone had an inhibitory influence. In most cases, both males and females were affected comparably. Opioid antagonist action was especially directed at cellular and tissue differentiation, with marked changes in macroscopic and areal dimensions and histotypic organization observed in the cerebrum. A prominent effect on the cerebrum of the 1 mg/kg naltrexone group was a substantial increase in packing density of the neural cells, reflecting a reduced area for accommodating neural elements. Changes in the hippocampus were largely restricted to the 1 mg/kg group. However, the number of granule cells was increased in the dentate gyrus of the 50 mg/kg group, suggesting that opioid receptor blockade affects cell types undergoing postnatal proliferation. Cellular elements derived prior to naltrexone treatment (e.g., pyramidal neurons) were capable of being influenced in only differentiative capacity. Our results show that endogenous opioids are natural trophic factors in brain development and provide evidence for the crucial role of endogenous opioid-opioid receptor interaction in neuro-ontogeny.


Multidisciplinary approach for patients with esophageal cancer.
Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced. There are no screening recommendations for patients unless they have Barrett's esophagitis or a significant family history of this disease. Often, esophageal cancer is not diagnosed until patients present with dysphagia, odynophagia, anemia or weight loss. When symptoms occur, the stage is often stage III or greater. Treatment of patients with very early stage disease is fairly straight forward using only local treatment with surgical resection or endoscopic mucosal resection. The treatment of patients who have locally advanced esophageal cancer is more complex and controversial. Despite multiple trials, treatment recommendations are still unclear due to conflicting data. Sadly, much of our data is difficult to interpret due to many of the trials done have included very heterogeneous groups of patients both histologically as well as anatomically. Additionally, studies have been underpowered or stopped early due to poor accrual. In the United States, concurrent chemoradiotherapy prior to surgical resection has been accepted by many as standard of care in the locally advanced patient. Patients who have metastatic disease are treated palliatively. The aim of this article is to describe the multidisciplinary approach used by an established team at a single high volume center for esophageal cancer, and to review the literature which guides our treatment recommendations.


Development of postural adjustments during reaching in infants at risk for cerebral palsy from 4 to 18 months.
To investigate postural adjustments during reaching in infants at high risk for cerebral palsy (CP). Observational cohort study in which 25 infants at high risk (11 males, 14 females) and 11 infants with typical development (six males, five females) were assessed at 4, 6, and 18 months corrected age. Reaching movements were elicited during supported and unsupported sitting, while surface electromyography was recorded of arm, neck, and trunk muscles. Percentages of direction-specific adjustments (first level of control), and recruitment patterns and anticipatory activation (second level of control) were calculated. Statistical analyses were performed with a binomial generalized estimating equations model for dichotomous variables and a linear mixed model for continuous variables. Postural activity of infants at high risk for CP at 4 months was virtually similar to that of infants with typical development. At 18 months, infants at high risk differed from infants with typical development with less direction-specificity (median values 20% vs 58% at trunk and neck level, OR 0.38, 95% CI 0.18-0.82); longer latencies to trunk muscle activation; and less anticipatory activation (41% vs 55%, in any direction-specific muscle, OR 0.53, 95% CI 0.32-0.89). In unsupported sitting, results were largely similar to those in supported sitting. Infants at high risk for CP grew into a postural deficit: at 18 months they showed delayed development of direction-specificity, and postural dysfunction as evidenced by slower recruitment of postural muscles and less frequent anticipatory activation.


Miniscrew-assisted nonsurgical palatal expansion before orthognathic surgery for a patient with severe mandibular prognathism.
A transverse maxillary deficiency in an adult is a challenging problem, especially when it is combined with a severe anteroposterior jaw discrepancy. The demand for nonsurgical maxillary expansion might increase as patients and clinicians try to avoid a 2-stage surgical procedure-surgically assisted rapid palatal expansion followed by orthognathic surgery-and detrimental periodontal effects and relapse. In this regard, a miniscrew-assisted rapid palatal expansion was devised and used to treat a 20-year-old patient who had severe transverse discrepancy and mandibular prognathism. Sufficient maxillary orthopedic expansion with minimal tipping of the buccal segment was achieved preoperatively, and orthognathic surgery corrected the anteroposterior discrepancy. The periodontal soundness and short-term stability of the maxillary expansion were confirmed both clinically and radiologically. Effective incorporation of orthodontic miniscrews for transverse correction might help eliminate the need for some surgical procedures in patients with complex craniofacial discrepancies by securing the safety and stability of the treatment, assuming that the suture is still patent.


[Effect of ursolic acid on invasion and migration of hepatocellular carcinoma cells co-cultured with macrophages and the underlying mechanisms].
To investigate the effect of ursolic acid on the invasion and migration of hepatocellular carcinoma (HCC) cells co-cultured with macrophages, and to explore the underlying mechanisms. Methods: The migration and invasion ability of HCC cells in the co-culture system with or without ursolic acid intervention were evaluated by transwell assay. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, N-cadherin, and vimentin in HCC cells co-cultured with macrophages were detected by Western blot. Results: The migration and invasion ability and EMT were significantly enhanced when co-cultured with macrophages, and the expression of E-cadherin was significantly increased while N-cadherin and vimentin levels were significantly decreased. However, after ursolic acid treatment, the migration and invasion ability were significantly reduced, and the expression of E-cadherin was increased while N-cadherin and vimentin levels were decreased. Conclusion: Ursolic acid exerts inhibitory effect on the ability of migration, invasion, and EMT for HCC, which are enhanced by co-culturing with macrophages.


Epstein-Barr virus infection: basis of malignancy and potential for therapy.
The Epstein-Barr virus (EBV) is a human herpesvirus that is usually carried lifelong as an asymptomatic infection. EBV is the causative agent of infectious mononucleosis and has been linked to the development of several malignant tumours, including B-cell neoplasms such as Burkitt's lymphoma and Hodgkin's disease, certain forms of T-cell lymphoma, and some epithelial tumours, such as undifferentiated nasopharyngeal carcinoma and a proportion of gastric cancers. All these tumours are characterised by the presence of multiple extrachromosomal copies of the circular viral genome in the tumour cells and the expression of EBV-encoded latent genes, which appear to contribute to the malignant phenotype. An increasing understanding of the function of EBV latent genes and of the nature of the immune response to the virus is providing exciting new possibilities for the treatment of EBV-associated malignancies. For example, adoptive transfer of virus-specific cytotoxic T lymphocytes has already been of value in the treatment of EBV-positive B-cell lymphomas arising in post-transplant patients, and this approach is currently being investigated in other EBV-associated tumours. In addition, gene therapy offers the opportunity to deliver agents that might directly interfere with the function of specific EBV genes. This review summarises the role of EBV in malignancy. In particular, it focuses on the latent proteins as a basis for understanding how EBV might contribute to the process of transformation. Strategies to target EBV in tumours, potentially providing alternative therapeutic approaches, are also discussed.


Circulating pre-treatment T-cell receptor repertoire as a predictive biomarker in advanced or metastatic non-small-cell lung cancer patients treated with pembrolizumab alone or in combination with chemotherapy.
The circulating T-cell receptor (TCR) repertoire is a dynamic representation of overall immune responses in an individual. We prospectively collected baseline blood from patients treated with first-line pembrolizumab monotherapy or in combination with chemotherapy. TCR repertoire metrics were correlated with clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS) and immune-related adverse events (irAEs). We built a logistic regression classifier by fitting all four TCR-β repertoire metrics to the immune checkpoint inhibitor (ICI) CBR data. In the subsequent receiver operating characteristic (ROC) analysis of the resulting logistic regression model probabilities, the best cut-off value was selected to maximise sensitivity to predict CBR to ICI. We observed an association between reduced number of unique clones and CBR among patients treated with pembrolizumab monotherapy (cohort 1) [risk ratio = 2.86, 95% confidence interval (CI) 1.04-8.73, P = 0.039]. For patients treated with pembrolizumab plus chemotherapy (cohort 2), increased number of unique clones [hazard ratio (HR) = 2.96, 95% CI 1.28-6.88, P = 0.012] and Shannon diversity (HR = 2.73, 95% CI 1.08-6.87, P = 0.033), and reduced evenness (HR = 0.43, 95% CI 0.21-0.90, P = 0.025) and convergence (HR = 0.41, 95% CI 0.19-0.90, P = 0.027) were associated with improved PFS, while only an increased number of unique clones (HR = 4.62, 95% CI 1.52-14.02, P = 0.007) were associated with improved OS. Logistic regression models combining the TCR repertoire metrics improved the prediction of CBR (cohorts 1 and 2) and were strongly associated with PFS (cohort 1, HR = 0.38, 95% CI 0.19-0.78, P = 0.009) and OS (cohort 2, HR = 0.20, 95% CI 0.05-0.76, P < 0.0001). Reduced TCR conversion was associated with increased frequency of irAEs needing systemic steroid treatment. Combined pre-treatment circulating TCR metrics might serve as a predictive biomarker for clinical outcomes among patients with advanced non-small-cell lung cancer treated with pembrolizumab alone or in combination with chemotherapy.


Electrocardiographic deep learning for predicting post-procedural mortality: a model development and validation study.
Preoperative risk assessments used in clinical practice are insufficient in their ability to identify risk for postoperative mortality. Deep-learning analysis of electrocardiography can identify hidden risk markers that can help to prognosticate postoperative mortality. We aimed to develop a prognostic model that accurately predicts postoperative mortality in patients undergoing medical procedures and who had received preoperative electrocardiographic diagnostic testing. In a derivation cohort of preoperative patients with available electrocardiograms (ECGs) from Cedars-Sinai Medical Center (Los Angeles, CA, USA) between Jan 1, 2015 and Dec 31, 2019, a deep-learning algorithm was developed to leverage waveform signals to discriminate postoperative mortality. We randomly split patients (8:1:1) into subsets for training, internal validation, and final algorithm test analyses. Model performance was assessed using area under the receiver operating characteristic curve (AUC) values in the hold-out test dataset and in two external hospital cohorts and compared with the established Revised Cardiac Risk Index (RCRI) score. The primary outcome was post-procedural mortality across three health-care systems. 45 969 patients had a complete ECG waveform image available for at least one 12-lead ECG performed within the 30 days before the procedure date (59 975 inpatient procedures and 112 794 ECGs): 36 839 patients in the training dataset, 4549 in the internal validation dataset, and 4581 in the internal test dataset. In the held-out internal test cohort, the algorithm discriminates mortality with an AUC value of 0·83 (95% CI 0·79-0·87), surpassing the discrimination of the RCRI score with an AUC of 0·67 (0·61-0·72). The algorithm similarly discriminated risk for mortality in two independent US health-care systems, with AUCs of 0·79 (0·75-0·83) and 0·75 (0·74-0·76), respectively. Patients determined to be high risk by the deep-learning model had an unadjusted odds ratio (OR) of 8·83 (5·57-13·20) for postoperative mortality compared with an unadjusted OR of 2·08 (0·77-3·50) for postoperative mortality for RCRI scores of more than 2. The deep-learning algorithm performed similarly for patients undergoing cardiac surgery (AUC 0·85 [0·77-0·92]), non-cardiac surgery (AUC 0·83 [0·79-0·88]), and catheterisation or endoscopy suite procedures (AUC 0·76 [0·72-0·81]). A deep-learning algorithm interpreting preoperative ECGs can improve discrimination of postoperative mortality. The deep-learning algorithm worked equally well for risk stratification of cardiac surgeries, non-cardiac surgeries, and catheterisation laboratory procedures, and was validated in three independent health-care systems. This algorithm can provide additional information to clinicians making the decision to perform medical procedures and stratify the risk of future complications. National Heart, Lung, and Blood Institute.


Clinical impact of the new criteria for the diagnosis of diabetes mellitus.
In 1997 the American Diabetes Association lowered the threshold for diagnosis of diabetes from a fasting plasma glucose concentration of 7.8 mmol/l to 7.0 mmol/l and advised that the oral glucose tolerance test no longer be used in routine clinical practice. In 1999 the World Health Organization endorsed the reduction in fasting plasma glucose threshold but recommended retaining the oral glucose tolerance test for anyone with impaired fasting glucose (6.1 mmol/l-6.9 mmol/l). This Review discusses the impact of these changes on the prevalence of diabetes and examines the implications for individuals and specific high-risk groups. The phenotype of those diagnosed with diabetes and the predictive value for the development of complications according to the different criteria are compared. It is clear that these changes in diagnostic criteria have major importance both for individuals and for resource planning at a national level.


Chorionic villus sampling for first trimester diagnosis of beta-thalassaemia. Report of the first South African case.
The first South African report of chorionic villus sampling for molecular diagnosis of beta-thalassaemia in a 10-weeks' pregnant Indian Muslim woman is presented. The sampling procedure and molecular techniques for sexing the fetus and establishing whether it was affected by beta-thalassaemia are described. From the sample of villi obtained a male fetus was identified, using an X-Y-specific DNA probe. A preliminary family study on both parents, the affected proband and his 4 phenotypically normal siblings, revealed two informative restriction fragment length polymorphisms in the mother, but none in the father. It was therefore not possible to differentiate between the two beta-globin gene alleles of the father. The fetus thus had a 50% chance of being a heterozygote or a 50% risk of being affected. Synthetic oligonucleotide hybridization of parental and fetal DNA was attempted by the Genetics Unit of Johns Hopkins Hospital, Baltimore, but the fetal hybridization was unsuccessful. Results on the parents were obtained too late to be of assistance in the present pregnancy as the parents requested termination of the pregnancy before 16 weeks' gestation for religious reasons.


High-performance polyimine vitrimers from an aromatic bio-based scaffold.
Bio-based vitrimers represent a promising class of thermosetting polymer materials, pairing the recyclability of dynamic covalent networks with the renewability of non-fossil fuel feedstocks. Vanillin, a low-cost lignin derivative, enables facile construction of polyimine networks marked by rapid exchange and sensitivity to acid-catalyzed hydrolysis. Furthermore, the aromatic structure makes it a promising candidate for the design of highly aromatic networks capable of high-performance thermal and dimensional stability. Such properties are paramount in polymeric thermal protection systems. Here, we report on the fabrication of polyimine networks with particularly high aromatic content from a novel trifunctional vanillin monomer prepared from the nucleophilic aromatic substitution of perfluoropyridine (PFP) on a multi-gram scale (>20 g) in high yield (86%). The trifunctional aromatic scaffold was then crosslinked with various diamines to demonstrate tunable viscoelastic behavior and thermal properties, with glass transition temperatures (Tg) ranging from 9 to 147 °C, degradation temperatures (5% mass loss) up to approximately 370 °C, and excellent char yields up to 68% at 650 °C under nitrogen. Moreover, the vitrimers displayed mechanical reprocessability over five destruction/healing cycles and rapid chemical recyclability following acidic hydrolysis at mild temperatures. Our findings indicate that vitrimers possessing tunable properties and high-performance thermomechanical behavior can be easily constructed from vanillin and electrophilic aromatic scaffolds for applications in heat-shielding materials and ablative coatings.


Inflammatory mediators in exhaled breath condensate and peripheral blood of healthy donors and stable COPD patients.
Objective: The aim of this work was to compare matrix metalloproteinase-9 and -12, tissue inhibitor of metalloproteinase-1 and -4, and neutrophil elastase in exhaled breath condensate (EBC) and peripheral blood of patients with COPD. Methods: Peripheral blood and EBC samples from COPD patients and healthy donors were collected. In serum and EBC, MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 proteins were detected by ELISA. The mRNA expression levels of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in peripheral blood mononuclear cells (PBMCs) were analyzed by qRT-PCR. Results: The protein levels of MMP-9 (p=.034) and MMP-12 (p=.041) in the EBC of COPD smokers were higher than those of COPD never-smokers. The concentrations of TIMP-1 (p=.072) and TIMP-4 (p=.084) in the EBC of COPD smokers were higher than those of COPD never-smokers; however, the difference was not statistically significant. MMP-9 (r=-0.78, p<.0001) and TIMP-1 (r=-0.71, p<.0001) levels in EBC were significantly negatively correlated with pulmonary function FEV1%pred. The protein levels of MMP-12 (r=-0.37, p=.034) and TIMP-4 (r=-0.34, p=.041) were also negatively correlated with FEV1%pred. The expression of MMP-9, MMP-12, NE, TIMP-1, and TIMP-4 in PBMCs and serum of COPD smokers were significantly higher than those of control never-smokers (p<.05). Conclusions: Exhaled MMP-9, MMP-12, TIMP-1, and TIMP-4 levels increased in stable COPD patients and were negatively correlated with FEV1%pred, which suggests the usefulness of their measurement in EBC for the monitoring of airway inflammation. However, to better assess their diagnostic or prognostic value, larger studies are necessary.


Air Pollution Exposure and the Development of Chronic Rhinosinusitis in the Active Duty Population.
It has been shown that combat environment exposure, including burn pits that produce particulate matter 2.5 (PM2.5), is associated with lower respiratory tract disease in the military population with increased hypothetical risk of upper respiratory disease, but no study has been done that examines the effects of non-combat environmental exposures on the development of chronic rhinosinusitis (CRS) in the active duty population. The primary goal of this study is to evaluate how air pollution exposure correlates to the development of CRS in active duty service members in the United States. The military electronic medical record was queried for active duty service members diagnosed with CRS by an otolaryngologist between January 2016 and January 2018, who have never deployed, stationed in the United States from 2015 to 2018 (n = 399). For each subject, the 1-year mean exposure of PM2.5, particulate matter 10 (PM10), nitrogen dioxide (NO2), and ozone was calculated. The control group was comprised of the same criteria except these patients were diagnosed with cerumen impaction and matched to the case group by age and gender (n = 399). Pollution exposure was calculated based on the Environmental Protection Agency's data tables for each subject. Values were calculated using chi-square test for categorical variables and the Mann-Whitney U-test for continuous variables. Matched cases and controls (n = 399) with 33.1% male showed a statistically significant odds ratio (OR) of 5.99 (95% CI, 2.55-14.03) for exposure of every 5 µg/m3 of PM2.5 increase and the development of CRS when controlling for age, gender, and diagnosis year. When further adjusting for smoking status, the OR was still statistically significant at 3.15 (95% CI, 1.03-9.68). Particulate matter 10, ozone, and NO2 did not show any statistical significance. Odds ratios remained statistically significant when further adjusting for PM10 and ozone, but not NO2. Dose-dependent curves largely did not show a statistical significance; however, they did trend towards increased exposure of PM2.5 leading to an elevated OR. This study showed that PM2.5 exposure is a major independent contributor to the development of CRS. Exposure to elevated levels produced statistically significant odds even among smokers and remained significant when controlling for other measured pollutants. There is still much to be understood about the genesis of CRS. From a pollution exposure perspective, a prospective cohort study would better elucidate the risk of the development of CRS among those exposed to other pollutants.


Renal tumors exhibiting granular cytoplasm.
Renal epithelial neoplasms consist of a group of distinct genetic and clinical entities that occasionally have overlapping morphological features. Pronounced cytoplasmic granularity or eosinophilia may be seen in a number of tumor types, including conventional (clear-cell) carcinomas, papillary carcinomas, chromphobe carcinoma, collecting duct carcinomas, and oncocytomas. Mesenchymal neoplasms such as angiomyolipomas as well as metastatic lesions such as malignant melanoma may have marked epithelial features and cytoplasmic granularity, thus mimicking a renal epithelial tumor. The same can be said for adrenal cortical neoplasms, which sometimes may be confused clinically, radiographically, and pathologically with a renal neoplasm. Close attention to morphological and cytologic detail will solve the differential diagnosis in the majority of cases, although some will require ancillary studies such as histochemistry, immunohistochemistry, and election microscopy. In a small percentage of cases molecular genetic studies are required to properly classify the tumor.


Intensity of follow-up after pancreatic cancer resection.
The prognosis of patients diagnosed with pancreatic adenocarcinoma remains dismal. Of the 15-20 % of patients who are candidates for potentially curative resection, 66-92 % will develop recurrent disease. Although guidelines for surveillance in the postoperative setting exist, they are not evidence based, and there is wide variability of strategies utilized. Current surveillance guidelines as suggested by the National Comprehensive Cancer Network (NCCN) include routine history and physical, measurement of serum cancer-associated antigen 19-9 (CA19-9) levels, and computed tomographic imaging at 3- to 6-month intervals for the first 2 years, and annually thereafter. However, the lack of prospective clinical data examining the efficacy of different surveillance strategies has led to a variability of the intensity of follow-up and a lack of consensus on its necessity and efficacy. Recent therapeutic advances may have the potential to significantly alter survival after recurrence, but a careful consideration of current surveillance strategies should be undertaken to optimize existing approaches in the face of high recurrence and low survival rates.


Important roles of odontoblast membrane phospholipids in early dentin mineralization.
The objective of this study was to first identify the timing and location of early mineralization of mouse first molar, and subsequently, to characterize the nucleation site for mineral formation in dentin from a materials science viewpoint and evaluate the effect of environmental cues (pH) affecting early dentin formation. Early dentin mineralization in mouse first molars began in the buccal central cusp on post-natal day 0 (P0), and was first hypothesized to involve collagen fibers. However, elemental mapping indicated the co-localization of phospholipids with collagen fibers in the early mineralization area. Co-localization of phosphatidylserine and annexin V, a functional protein that binds to plasma membrane phospholipids, indicated that phospholipids in the pre-dentin matrix were derived from the plasma membrane. A 3-dimensional in vitro biomimetic mineralization assay confirmed that phospholipids from the plasma membrane are critical factors initiating mineralization. Additionally, the direct measurement of the tooth germ pH, indicated it to be alkaline. The alkaline environment markedly enhanced the mineralization of cell membrane phospholipids. These results indicate that cell membrane phospholipids are nucleation sites for mineral formation, and could be important materials for bottom-up approaches aiming for rapid and more complex fabrication of dentin-like structures.


Weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced colorectal cancer: Taiwan experience.
Between January 1994 and November 1995, 41 patients with metastatic colorectal carcinoma were enrolled in this study. All these patients had recurrent disease after a prior 5-fluorouracil based adjuvant chemotherapy or failed to achieve response by prior chemotherapy that included 5-fluorouracil. 5-Fluorouracil, 2600 mg/m2, was administered concurrently with 100 mg/m2 leucovorin over 24 hours of continuous intravenous infusion. The treatment was repeated every week until progressive disease was documented. Forty-one patients received a total of 810 courses of treatment. The overall response rate was 17.1% (95% confidence interval 5.6-28.6%). In two patients who achieved complete response, the liver was the metastatic site. The median survival was 18.4 months for responders and 12.6 months for non-responders. Gastrointestinal toxicities including diarrhea, stomatitis, nausea and vomiting were the major side-effects. Sixteen incidences (39.0%) of grade 2-3 gastrointestinal toxicities were observed. One patient (2.4%) developed a grade 3 cardiac toxicity, and another one (2.4%) had a grade 2 neurotoxicity. Hematological toxicities were minimal with no evidence of severe (grade 2 or more) leukopenia or thrombocytopenia. We conclude that in patients with pretreated metastatic colorectal cancer, weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin is associated with higher efficacy and tolerable toxicity. This regimen is a good option as a second-line treatment for those whose diseases are recurrent from or refractory to prior 5-fluorouracil, and deserves a longer period of follow-up.


Solubility of nitrogen in marine mammal blubber depends on its lipid composition.
Understanding the solubility of nitrogen gas in tissues is a crucial aspect of diving physiology, especially for air-breathing tetrapods. Adipose tissue is of particular interest because of the high solubility of nitrogen in lipids. Surprisingly, nothing is known about nitrogen solubility in the blubber of any marine mammal. We tested the hypothesis that N(2) solubility is dependent on the lipid composition of blubber; most blubber is composed of triacylglycerols, but some toothed whales deposit large amounts of waxes in blubber instead. The solubility of N(2) in the blubber of 13 toothed whale species ranged from 0.062 to 0.107 ml N(2) ml(-1) oil. Blubber with high wax ester content had higher N(2) solubility, observed in the beaked (Ziphiidae) and small sperm (Kogiidae) whales, animals that routinely make long, deep dives. We also measured nitrogen solubility in the specialized cranial acoustic fat bodies associated with echolocation in a Risso's dolphin; values (0.087 ml N(2) ml(-1) oil) were 16% higher here than in its blubber (0.074 ml N(2) ml(-1) oil). As the acoustic fats of all Odontocetes contain waxes, even if the blubber does not, these tissues may experience greater interaction with N(2). These data have implications for our understanding and future modeling of diving physiology in Odontocetes, as our empirically derived values for nitrogen solubility in toothed whale adipose were up to 40% higher than the numbers traditionally assumed in marine mammal diving models.


Effects of cholesterol on (Na+,K+)-ATPase ATP hydrolyzing activity in bovine kidney.
The (Na+,K+)-ATPase ATP hydrolyzing activity from rabbit kidney medulla basolateral membrane vesicles was studied as a function of the cholesterol content of the basolateral membranes. The cholesterol content of the membranes was modified by incubation with phospholipid vesicles. When the cholesterol content was increased above that found in the native membrane, the (Na+,K+)-ATPase ATP hydrolyzing activity was inhibited. When the cholesterol content was decreased from that found in the native membranes, the (Na+,K+)-ATPase ATP hydrolyzing activity was inhibited. Analogous effects were found with the K+-activated phosphatase activity of the same membrane vesicles. Therefore, at low cholesterol contents, cholesterol was stimulatory, and at high cholesterol contents, cholesterol was inhibitory. The structural specificity of this effect was tested by introducing lanosterol and ergosterol as 50% of the membrane sterol. Ergosterol was the least effective at supporting (Na+,K+)-ATPase ATP hydrolyzing activity, while lanosterol was more effective, but still not as effective as cholesterol.


Numerical simulation of air flow and medical-aerosol distribution in an innovative nebulizer hood.
The use of a hood to administer therapeutic aerosols to wheezy infants has many advantages and was found as efficient as administration using a mask. The aim of the present study is to investigate numerically the airflow induced drug dispersion inside the hood. Drug droplet dispersion is examined with respect to three breathing phases: inspiration, expiration, and apnea. The governing equations describing the airflow and the trajectories of drug droplets were solved using the FLUENT 6.1 Computational Fluid Dynamics (CFD) software package. The geometry and mesh were generated with the GAMBIT package. The velocity field of the air and the trajectories of drug droplets inside the funnel--the tube that delivers the drug from the nebulizer to the infant's mouth--and close to its exit are robust and do not show any appreciable differences among the three breathing phases studied. However, in other parts of the hood, air velocity, and particle motion largely depend on the infant's breathing and physiological state. The efficiency of drug delivery to the mouth during inspiration is found to be as high as 84%, whereas it is much smaller in the other two (common) breathing phases examined. Our results may be utilized to improve the hood design and to increase its efficacy for administration of aerosolized medications to infants.


Equipoise in Appropriate Initial Volume Resuscitation for Patients in Septic Shock With Heart Failure: Results of a Multicenter Clinician Survey.
International clinical practice guidelines call for initial volume resuscitation of at least 30 mL/kg body weight for patients with sepsis-induced hypotension or shock. Although not considered in the guidelines, preexisting cardiac dysfunction may be an important factor clinicians weigh in deciding the quantity of volume resuscitation for patients with septic shock. We conducted a multicenter survey of clinicians who routinely treat patients with sepsis to evaluate their beliefs, behaviors, knowledge, and perceived structural barriers regarding initial volume resuscitation for patients with sepsis and concomitant heart failure with reduced ejection fraction (HFrEF) <40%. Initial volume resuscitation preferences were captured as ordinal values, and additional testing for volume resuscitation preferences was performed using McNemar and Wilcoxon signed rank tests as indicated. Univariable logistic regression models were used to identify significant predictors of ≥30 mL/kg fluid administration. A total of 317 clinicians at 9 US hospitals completed the survey (response rate 47.3%). Most respondents were specialists in either internal medicine or emergency medicine. Substantial heterogeneity was found regarding sepsis resuscitation preferences for patients with concomitant HFrEF. The belief that patients with septic shock and HFrEF should be exempt from current sepsis bundle initiatives was shared by 39.4% of respondents. A minimum fluid challenge of ∼30 mL/kg or more was deemed appropriate in septic shock by only 56.4% of respondents for patients with concomitant HFrEF, compared to 89.1% of respondents for patients without HFrEF (P < .01). Emergency medicine physicians were most likely to feel that <30 mL/kg was most appropriate in patients with septic shock and HFrEF. Clinical equipoise exists regarding initial volume resuscitation for patients with sepsis-induced hypotension or shock and concomitant HFrEF. Future studies and clinical practice guidelines should explicitly address resuscitation in this subpopulation.