Isolation and characterization of posterofrontal/sagittal suture mesenchymal cells in vitro.
Craniosynostosis, the premature fusion of cranial sutures, affects one in 2500 children. In the mouse, the posterofrontal suture is programed to fuse postnatally, but the adjacent sagittal suture remains patent throughout life. To study the cellular process of suture fusion, the authors isolated and studied suture-derived mesenchymal cells. Skulls were harvested from 80 mice (2 to 5 days old), and posterofrontal and sagittal sutures were dissected meticulously. Suture mesenchymal tissue was separated from the underlying dura mater and overlying pericranium and cultured in growth media. After the cells migrated from the explant tissues, the morphologies of the two cell populations were studied carefully, and quantitative real-time polymerase chain reaction was performed to evaluate gene expression. Both posterofrontal and sagittal cells exhibited highly heterogeneous morphologies, and the posterofrontal cells migrated faster than the sagittal cells. Accordingly, growth factors such as transforming growth factor-beta1 and fibroblast growth factor (FGF)-2 were expressed significantly more highly in posterofrontal compared with sagittal suture mesenchymal cells. In contrast, FGF receptor 2 and FGF-18 were expressed significantly more in sagittal than in posterofrontal suture cells. Importantly, bone morphogenic protein-3, the only osteogenic inhibitor in the bone morphogenic protein family, and noggin, a bone morphogenic protein antagonist, were expressed significantly more in sagittal than in posterofrontal suture cells, suggesting a possible mechanism of suture patency. To the authors' knowledge, this is the first analysis of mouse suture-derived mesenchymal cells. The authors conclude that isolation of suture-derived mesenchymal cells will provide a useful in vitro system with which to study the mechanisms underlying suture biology.


Prediction of childhood drowning and near-drowning morbidity and mortality.
(a) Evaluate the presenting hemodynamic status and neurologic function of a series of warm water submersion injuries. (b) To ascertain the importance of the timing of the neurologic examination. (c) To identify risk factors that predict which patients will not return to presubmersion status. Retrospective review of all patients with a diagnosis of drowning/near-drowning responded to by the Children's Hospital pediatric transport service. Data were collected over a 24-month period regarding patient characteristics, submersion medium, rescue efforts, time out of sight, elapsed times to emergency department (ED) and pediatric intensive care unit (PICU) arrival, neurologic and hemodynamic status on arrival at the ED and PICU, reconstructed Conn-Modell category, and neurologic outcome. EDs of the referring hospitals and PICU of the Children's Hospital of Orange County (CHOC), California. Ninety-three submersion victims at an average age of 31 months. All patients were provided intensive care support. None. Twenty-three percent (21/ 93) of patients died or survived vegetative. No patient arriving comatose and asystolic in the ED survived neurologically intact (n = 21, three patients expired in the ED). This group of patients had a mean duration of documented asystole = 41 minutes, range of 18 to 107 minutes, and time to ED arrival = 21 minutes. All patients with a detectable pulse and blood pressure (n = 72) on arrival to the ED, regardless of their neurologic status, recovered to their presubmersion status. Patients arriving comatose (decorticate, decerebrate, or flaccid posture) in the PICU (n = 18, mean arrival = 192 minutes) all died or were vegetative. All patients with non-coma (n = 72, Conn-Modell category A or B) on arrival to the PICU recovered normally. Hemodynamic status in the ED and neurologic status in the PICU are highly predictive of outcome. On arrival to the ED, the cardiovascular status is more predictive of abnormal outcome than neurologic status. Poor neurologic outcome appears inevitable for warm water submersion victims who are asystolic at ED arrival and remain comatose for more than 200 minutes.


Host location in flow by larvae of the symbiotic barnacle Trevathana dentata using odour-gated rheotaxis.
The detection and location of specific organisms in the aquatic environment, whether they are mates, prey or settlement sites, are two of the most important challenges facing aquatic animals. Large marine invertebrates such as lobsters have been found to locate specific organisms by navigating in the plume of chemicals emitted by the target. However, active plume tracking in flow by small organisms such as marine larvae has received little scientific attention. Here, we present results from a study examining host location in flow by nauplius larvae of the barnacle Trevathana dentata, which inhabits the stony reef coral Cyphastrea chalcidicum. The experiments included analysis of larval motion in an annular flume under four conditions: (i) still water, (ii) in flow, (iii) in still water with waterborne host metabolites and (iv) in flow with host metabolites. Our results show that T. dentata nauplii are unable to locate their target organism in still water using chemotaxis, but are capable of efficient host location in flow using odour-gated rheotaxis. This technique may enable host location by earlier, less-developed larval stages.


Silica and nitrogen modulate physical defense against chewing insect herbivores in bioenergy crops Miscanthus x Giganteus and Panicum virgatum (Poaceae).
Feedstock crops selected for bioenergy production to date are almost exclusively perennial grasses because of favorable physiological traits that enhance growth, water use, and nutrient assimilation efficiency. Grasses, however, tend to rely primarily on physical defenses, such as silica, to deter herbivores. Silica impedes processing of feedstocks and introduces a trade-off between managing for cost efficiency (i.e., yield) and plant defenses. To test how silica modulates herbivory in two of the most preferred feedstock crops for production across the central United States, miscanthus (Miscanthus x giganteus Greef and Deuter ex Hodkinson and Renvoize) and switchgrass (Panicum virgatum L.), we examined the performance of two immature generalist insect herbivores, fall armyworm (Spodoptera frugiperda (J.E. Smith) and the American grasshopper [Schistocerca americana (Drury)], on grasses grown under silica and nitrogen amendment. Both miscanthus and switchgrass assimilated nitrogen and silica when grown in amended soil that altered the consumption and conversion efficiency of herbivores consuming leaf tissue. The magnitude of nutrient assimilation, however, depended on intrinsic plant traits. Nitrogen increased conversion efficiency for both fall armyworm and American grasshopper but increased consumption rate only for fall armyworm. Silica reduced conversion efficiency and increased consumption rate only for the American grasshopper. Because of this variability, management strategies that reduce silica or increase nitrogen content in feedstock crops to enhance yields may directly influence the ability of bioenergy grasses to deter certain generalist herbivores.


The thermal-circulatory ratio (TCR): An index to evaluate the tolerance to heat.
Introduction The common practice in the Israel Defense Force is that all exertional heat related injuries victims undergo a heat tolerance test (HTT) as a part of the "return to duty" process. The purpose of this study was to develop a quantitative, supportive physiological index for the assessment of the HTT based on the understanding that heat strain level should combine the thermal and cardiovascular strains. Materials and methods The HTT results of 104 individuals with a history of heat injuries were retrospectively analyzed after randomly divided into two groups (an analysis group and a validation group). Rectal temperature and heart rate were monitored continuously during the test. Using the ratio between those two variables we constructed the TCR (Thermal-Circulatory Ratio) index and defined thresholds for determining heat tolerance based on the HTT. Results Using a TCR value of 0.279 [°C/bpm] or less after completing the 120 min HTT can be used as a significant measure to distinguish between heat tolerance and heat intolerance individuals with sensitivity and specificity of 100% of 89%, respectively. In addition, a TCR value of 0.320 [°C/bpm] or less calculated after 60 min was found as a significant measure to determine heat tolerance with 100% sensitivity and 69% specificity. The latter threshold may assist in significantly shortening the HTT for those individuals whose TCR value matches this criterion. Discussion and conclusion A new index (TCR) that combines the thermal and cardiovascular responses to exercise-heat stress was found to be a valid measure, with high sensitivity and specificity, to support the distinguishing between heat tolerance and heat intolerance individuals following a HTT. Furthermore, the suggested index may enable to shorten the HTT, which will make the test more efficient.


Potential molecular prognostic markers in head and neck squamous cell carcinomas.
Current management strategies for squamous cell carcinoma of the head and neck (HNSCC) rely on an understanding of the natural history of the disease, along with the use of prognostic factors to guide selection of appropriate treatment. However, it is recognized that tumor heterogeneity limits the reliable use of currently available prognostic markers. With the evolving understanding of the genetic and molecular basis of human malignancies, there has been much interest in determining whether specific molecular changes in HNSCC might guide treatment decisions. A literature review of potential molecular markers relevant to HNSCC was undertaken and evaluated. It is evident that the published information is promising but, oftentimes, limited by a scarcity of large, uniformly staged and treated patients, from which the value of novel molecular markers can be assessed. On the basis of the review of more than 100 articles, some of the emerging molecular markers that might provide independent prognostic information include epidermal growth factor receptor (EGFR), transforming growth factor-alpha (TGF-alpha), cyclin D1, and p53. This review will discuss the current status of these molecular factors and consequent implications for novel therapeutic approaches for patients with HNSCC. With the evolving understanding that human malignancies have developed and progressed on the basis of accumulated molecular abnormalities, there is an existing body of work trying to determine whether such abnormalities can predict clinical behavior of HNSCC. Such studies have to be conducted rigorously to derive useful information. Nevertheless, the role of such molecular markers, and the possibility to exploit them for therapeutic gain, is already at the horizon.


Early spontaneous deficiency of calcitonin renal binding sites in rats with a high incidence of calcitonin-secreting tumors (WAG/Rij).
Old rats of the WAG/Rij strain have a high incidence (50%) of medullary thyroid carcinoma, a calcitonin (CT)-secreting tumor. We have characterized and quantified the topographical distribution of [125I]salmon calcitonin (sCT) binding sites in the kidneys of this strain, as compared to Wistar CF rats (2% incidence of spontaneous medullary thyroid carcinoma). We report here that, up to 15 days of postnatal development, the distribution of CT-binding sites in the kidney of the WAG/Rij strain was quite similar to that found in developing and adult Wistar CF rats. However, from the age of 1 month, sCT-binding sites were dramatically reduced in both the medulla and the inner part of the kidney cortex, though plasma CT levels were not significantly different in both strains. Adult WAG/Rij rats bearing a transplanted tumor for 12 weeks had a high level of plasma calcitonin and exhibited an even greater reduction of both medullary and cortical sCT-binding sites. These results suggest that the modification in the CT-binding sites in WAG/Rij rats is not a consequence of a possible down regulation due to elevated circulating hormonal level but could be inherited and possibly associated with the later development of the tumor in this strain.


Identifying the start of a platelet aggregate by the shear rate and the cell-depleted layer.
Computer simulations were performed to study the transport of red blood cells and platelets in high shear flows, mimicking earlier published in vitro experiments in microfluidic devices with high affinity for platelet aggregate formation. The goal is to understand and predict where thrombus formation starts. Additionally, the need of cell-based modelling in these microfluidic devices is demonstrated by comparing our results with macroscopic models, wherein blood is modelled as a continuous fluid. Hemocell, a cell-based blood flow simulation framework is used to investigate the transport physics in the microfluidic devices. The simulations show an enlarged cell-depleted layer at the site where a platelet aggregate forms in the experiments. In this enlarged cell-depleted layer, the probability to find a platelet is higher than in the rest of the microfluidic device. In addition, the shear rates are sufficiently high to allow for the von Willebrand factor to elongate in this region. We hypothesize that the enlarged cell-depleted layer combined with a sufficiently large platelet flux and sufficiently high shear rates result in an haemodynamic environment that is a preferred location for initial platelet aggregation.


Differences in BMI between Mexican and Colombian patients receiving antipsychotics: results from the International Study of Latinos on Antipsychotics (ISLA).
Objective: The objective of this study is to examine the association of country of residence with body mass index (BMI) between Mexican and Colombian patients exposed to antipsychotics. We hypothesize that there will be a significant association between country of residence and BMI and that Mexican patients will have higher BMI than their Colombian counterparts.Design: The International Study of Latinos on Antipsychotics (ISLA) is a multisite, international, cross sectional study of adult Latino patients exposed to antipsychotics in two Latin American Countries (i.e. Mexico and Colombia). Data were collected from a total of 205 patients (149 from Mexico and 56 from Colombia). The sites in Mexico included outpatient clinics in Mexicali, Monterrey and Tijuana. In Colombia, data were collected from outpatient clinics in Bogotá. For this study we included patients attending outpatient psychiatric community clinics that received at least one antipsychotic (new and old generation) for the last 3 months. A linear regression model was used to determine the association of country of residence with BMI for participants exposed to an antipsychotic.Results: After controlling for demographics, behaviors, biological and comorbid psychiatric variables, there was a significant difference between Colombia vs. Mexico in the BMI of patients exposed to antipsychotics (β = 4.9; p < 0.05).Conclusion: Our hypotheses were supported. These results suggest that differences in BMI in patients exposed to antipsychotics in Mexico and Colombia may reflect differences in prevalence of overweight/obesity at the population level in the respective countries, and highlights the involvement of other risk factors, which may include genetics.


Resistance exercise increases NF-κB activity in human skeletal muscle.
Intense resistance exercise causes a significant inflammatory response. NF-κB has been identified as a prospective key transcription factor mediating the postexercise inflammatory response. The purpose of this study was to determine whether a single bout of intense resistance exercise regulates NF-κB signaling in human skeletal muscle. Muscle biopsy samples were obtained from the vastus lateralis of five recreationally active, but not strength-trained, males (21.9 ± 1.3 yr) prior to, and at 2 and 4 h following, a single bout of intense resistance exercise. A further five subjects (4 males, 1 female) (23 ± 0.89 yr) were recruited as a nonexercise control group to examine the effect of the muscle biopsy protocol on key markers of skeletal muscle inflammation. Protein levels of IκBα and phosphorylated NF-κB (p65), as well as the mRNA expression of inflammatory myokines monocyte chemoattractant protein 1 (MCP-1), IL-6, and IL-8 were measured. Additionally, NF-κB (p65) DNA binding to the promoter regions of MCP-1, IL-6, and IL-8 was investigated. IκBα protein levels decreased, while p-NF-κB (p65) protein levels increased 2 h postexercise and returned to near-baseline levels by 4-h postexercise. Immunohistochemical data verified these findings, illustrating an increase in p-NF-κB (p65) protein levels, and nuclear localization at 2 h postexercise. Furthermore, NF-κB DNA binding to MCP-1, IL-6, and IL-8 promoter regions increased significantly 2 h postexercise as did mRNA levels of these myokines. No significant change was observed in the nonexercise control group. These novel data provide evidence that intense resistance exercise transiently activates NF-κB signaling in human skeletal muscle during the first few hours postexercise. These findings implicate NF-κB in the transcriptional control of myokines known to be central to the postexercise inflammatory response.


Evaluation of subcutaneous administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius).
To evaluate SC administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). 12 healthy juvenile ball pythons. In a randomized crossover study, each snake was administered a combination of alfaxalone (5 mg/kg [2.3 mg/lb]) and midazolam (0.5 mg/kg [0.23 mg/lb]) and a combination of dexmedetomidine (0.05 mg/kg [0.023 mg/lb]) and midazolam (0.5 mg/kg), SC, with a washout period of at least 7 days between protocols. Respiratory and heart rates and various reflexes and behaviors were assessed and compared between protocols. Forty-five minutes after protocol administration, sedation was reversed by SC administration of flumazenil (0.05 mg/kg) alone or in combination with atipamezole (0.5 mg/kg; dexmedetomidine-midazolam protocol only). Because of difficulties with visual assessment of respiratory effort after sedative administration, the experiment was repeated for a subset of 3 ball pythons, with plethysmography used to assess respiration. Both protocols induced a similar level of moderate sedation with no adverse effects aside from transient apnea. Cardiopulmonary depression was more profound, but time to recovery after reversal was significantly shorter, for the dexmedetomidine-midazolam protocol than for the alfaxalone-midazolam protocol. Plethysmographic findings were consistent with visual observations and suggested that snakes compensated for a decrease in respiratory rate by increasing tidal volume amplitude. Results indicated that both protocols induced clinically relevant sedation in ball pythons and should be useful for minor procedures such as venipuncture and diagnostic imaging. However, caution should be used when sedating snakes with compromised cardiopulmonary function. (J Am Vet Med Assoc 2020;256:573-579.


Risk factors for DSM-III-R posttraumatic stress disorder: findings from the National Comorbidity Survey.
The present study examined the association of childhood risk factors with exposure to traumas and posttraumatic stress disorder (PTSD). PTSD is a unique symptom configuration after exposure to an unusual, extreme event. Data come from the US National Comorbidity Study of 5,877 respondents aged 15-54 years conducted between September 1990 and February 1992. The risk factors examined were preexposure affective, anxiety, and substance use disorders; parental mental and substance use disorders; parental aggression toward the respondent and toward the other parent; and a nonconfiding relationship with the mother during childhood. Analyses were stratified by gender and adjusted for demographic variables and traumatic experiences prior to the index trauma. The occurrence of trauma was associated with many risk factors in women but few in men. Similarly, more risk factors predicted PTSD in women than in men. Overall, when respondents were grouped into broad trauma categories, an increase in the number of risk factors was associated with higher rates of PTSD. However, in analyses of the trauma subsample that adjusted for individual type of trauma (e.g., rape, physical attack), only one risk factor (history of affective disorder) predicted PTSD in women, and two (history of anxiety disorder and parental mental disorder) predicted PTSD in men. The results thus indicate that although these risk factors have an important association with PTSD, they operate largely by predicting trauma exposure rather than by predicting the onset of disorder after exposure.


Benign hepatic adenoma associated with oral contraceptive use mimicking pelvic inflammatory disease. A case report.
An increased incidence of benign hepatic adenoma among users of oral contraceptives has been reported by several investigators during the past ten years. The majority of patients present with right-upper-quadrant pain, often associated with an upper abdominal mass. Our patient had an unusual clinical presentation simulating pelvic inflammatory disease. The appropriate diagnosis was reached with the aid of pelvic and abdominal sonography, liver-spleen scan and culdocentesis. The definitive management is partial hepatectomy, although there are reports of complete regression without surgery in minimally symptomatic patients following cessation of oral contraceptives.


Relationship between psychological inflexibility and experiential avoidance and internet addiction: Mediating effects of mental health problems.
Internet addiction became a major mental health problem in college student. Our objective was to examine the relationship between psychological inflexibility and experiential avoidance (PIEA) and Internet addiction (IA) and the mediating effects of mental health problem indicators. 500 college students (238 men and 262 women) participated in this study. The level of PIEA was examined using the Acceptance and Action Questionnaire-II. The severity of IA was assessed using the Chen Internet Addiction Scale. The levels of depression, anxiety, interpersonal sensitivity, and hostility were evaluated using the Symptom Checklist-90 item-Revised Scale. The relationship among PIEA, mental health problems, and IA was examined using structural equation modeling. The severity of PIEA was positively associated with the severity of IA as well as positively associated with the severity of mental health problems. In addition, the severity of mental health problem indicators was positively associated with the severity of IA. These results provide the severity of PIEA is directly related to the severity of IA and indirectly related to the severity of IA through increasing the severity of mental health problems. The PIEA should be one of the target objectives when administer cognitive-behavioral therapy to college students with IA and mental health problems.


In vitro reparative dentin: a biochemical and morphological study.
In this study, starting from human dental pulp cells cultured in vitro, we simulated reparative dentinogenesis using a medium supplemented with different odontogenic inductors. The differentiation of dental pulp cells in odontoblast-like cells was evaluated by means of staining, and ultramorphological, biochemical and biomolecular methods. Alizarin red staining showed mineral deposition while transmission electron microscopy revealed a synthesis of extracellular matrix fibers during the differentiation process. Biochemical assays demonstrated that the differentiated phenotype expressed odontoblast markers, such as Dentin Matrix Protein 1 (DMP1) and Dentin Sialoprotein (DSP), as well as type I collagen. Quantitative data regarding the mRNA expression of DMP1, DSP and type I collagen were obtained by Real Time PCR. Immunofluorescence data demonstrated the various localizations of DSP and DMP1 during odontoblast differentiation. Based on our results, we obtained odontoblast-like cells which simulated the reparative dentin processes in order to better investigate the mechanism of odontoblast differentiation, and dentin extracellular matrix deposition and mineralization.


A Raman spectroscopic study of the carbon deposition mechanism on Ni/CGO electrodes during CO/CO2 electrolysis.
In situ and ex situ Raman analyses of porous Ni/CGO electrodes reveal differences in the amount, location and type of carbon formed during CO/CO2 electrolysis. The results demonstrate the limitations of optical in situ techniques applied to Solid Oxide Cells (SOCs) operated in electrolysis conditions. Increased carbon deposition close to the electrode-electrolyte interface is likely to be the result of high charge-transfer current in that area. The positive effect of a CGO interlayer on reducing carbon formation on the fuel electrode is demonstrated.


Milrinone in heart failure. Acute effects on left ventricular systolic function and myocardial metabolism.
Milrinone, a new bipyridine compound related to amrinone, is a potent non-adrenergic inotrope in experimental preparations and also shows vasodilator activity. In the present study the haemodynamic and metabolic effects of milrinone were evaluated in 12 patients with congestive heart failure. Milrinone 5 mg given orally produced a sharp reduction in left ventricular end diastolic pressure without significantly affecting stroke volume. The improvement in left ventricular function was due to a combination of vasodilation and positive inotropism. Thus small reductions in blood pressure and systemic vascular resistance were associated with increments in the isovolumic indices of left ventricular function. The relation between left ventricular end systolic pressure and dimension was displaced leftwards and downwards. Only reductions in left ventricular cavity dimension were statistically significant, however. Though myocardial oxygen consumption did not change significantly, it tended to increase whereas lactate consumption tended to decrease. This trend towards oxygen imbalance suggests the need for caution in the use of milrinone in patients with severe coronary artery disease.


A combination of the metabolic enzyme inhibitor APO866 and the immune adjuvant L-1-methyl tryptophan induces additive antitumor activity.
Many types of malignant cells have a higher nicotinamide adenine dinucleotide (NAD) turnover rate than normal cells, as well as the ability to escape immune responses. Indoleamine 2,3-dioxygenase (IDO) is reported to be a negative immune regulator. Overexpression of IDO in dendritic cells is observed in tumor-draining lymph nodes. IDO-expressing dendritic cells suppress T-cell activation and promote immune tolerance. The nicotinamide phosphoribosyl transferase (NAMPT) inhibitor APO866 (also called FK866 or WK175) selectively inhibits tumor growth through intracellular NAD depletion. The IDO-specific inhibitor L-1-methyl-tryptophan (L-1MT) activates immune responses and reduces tumor volume in murine tumor models. We combined L-1MT and APO866 treatments and tested their antitumor effects in the murine gastric and bladder tumor models. In immune-competent mice, a combination of APO866 and L-1MT had a better therapeutic effect than did either L-1MT or APO866 alone. The intracellular level of NAD was suppressed by APO866 but not L-1MT. However, an additive inhibitory effect on tumor growth was not observed in tumor-bearing immune-deficient mice. The new strategy of combining a metabolic inhibitor and an immune adjuvant induced a potent therapeutic effect.


Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation.
Most mammals are coated with pigmented hair. Melanocytes in each hair follicle produce melanin pigments for the hair during each hair cycle. The key to understanding the mechanism of cyclic melanin production is the melanocyte stem cell (MelSC) population, previously known as 'amelanotic melanocytes'. The MelSCs directly adhere to hair follicle stem cells, the niche cells for MelSCs and reside in the hair follicle bulge-subbulge area, the lower permanent portion of the hair follicle, to serve as a melanocyte reservoir for skin and hair pigmentation. MelSCs form a stem cell system within individual hair follicles and provide a 'hair pigmentary unit' for each cycle of hair pigmentation. This review focuses on the identification of MelSCs and their characteristics and explains the importance of the MelSC population in the mechanisms of hair pigmentation, hair greying, and skin repigmentation.


Hormonal Contraceptive Use in Football Codes in Australia.
The recent launch of the new National elite women's football competitions in Australia has seen a 20-50% increase in grassroots female participation. With the growing participation across grassroots to elite competitions, understanding the health of female athletes should be prioritized. In elite level athletes, hormonal contraceptive (HC) use is common (~50%), however, little is known about the prevalence and reasons for use and disuse of HC in elite female football athletes. As such, the impact of HC use is often not considered when monitoring the health of female footballers. This study involved a subset of data collected as part of a larger questionnaire investigating menstrual cycle function, hormonal contraception use, and the interaction with training load volume and perceived performance in elite female football code athletes. A total of 177 participants completed the questionnaire across three football codes within Australia (rugby league, rugby union/sevens, Australian football). One third (n = 58) of athletes were currently using HC, predominately in the form of an oral contraceptive pill (OC, n = 47). Reasons for use included: to avoid pregnancy (71%); to control/regulate cycle (38%); and to reduce menstrual pain (36%). However, most athletes using an OC (89%) could not identify the type of pill used (e.g., mono-, bi-, or triphasic). The main reason for disuse was due to the negative side effects (n = 23), such as mood swings, weight gain, and depression/anxiety. Comparing HC users and non-users, there were no statistical differences in the number of reported menstrual symptoms, use of medication to relieve menstrual pain, or frequency for needing to adapt training due to their menstrual cycle (p > 0.05). Since most athletes were unaware of the type of OC they used, female football athletes require further education about the different types of HC, and specifically OC, available to them. Similarities in the symptoms experienced, pain management, and training adaptation requirements between groups suggests that HC use may not have the intended outcome for certain athletes. As such, greater awareness of athlete's personal experiences with the menstrual cycle, how HC may influence their experience, and acknowledgment of non-pharmacological methods to help manage menstrual cycle related symptoms are warranted.


Environmental information content of ocean ambient noise.
In recent years, methods have been developed to estimate a variety of environmental parameters based on measurements of the ocean ambient noise. For example, noise has been used to estimate water depth using the passive fathometer technique and bottom loss estimated and used to invert for seabed parameters. There is also information in the noise about the water column sound speed, volume attenuation, and the sea-state. The Fisher information can be used to quantify the basic information available in the noise measurements and its inverse, the Cramér-Rao lower bound (CRLB), provides the lower limit on the variance of an unbiased estimator of a particular parameter. The CRLB can be used to study the feasibility of various measurement configurations and parameter sensitivities. In this paper, the CRLB is developed for ocean ambient noise and the environmental information contained in the measurements is determined. The CRLBs provide an estimate of the underlying information in the data, however, it is independent of the estimation methodology. This is useful to determine if a given estimation method is reaching the lower bound. Results illustrating the bounds as well as sensitivities and performance of estimators are demonstrated using both simulations and data.


Purification and characterization of proteases from Bacillus amyloliquefaciens isolated from traditional soybean fermentation starter.
Bacillus amyloliquefaciens FSE-68 isolated from meju, a Korean soybean fermentation starter, was identified on the basis of biophysical tests and 16S rRNA gene sequence. A neutral metalloprotease (NPR68) and an alkaline serine-protease (APR68) were purified by ammonium sulfate precipitation and cation exchange chromatography and identified on the basis of their activities at different pH values and the selective protease inhibitors. The molecular weights of NPR68 and APR68 measured with ESI-MS were 32743 (+/- 0.8) and 27443 (+/- 0.5) Da, respectively. Against oxidized insulin chains, the NPR68 has a cleavage preference at the site where leucine is located as a P1' residue followed by phenylalanine, and the APR68 has broad specificity and favors leucine at the P1 site. These results indicate that the proteases are natural variants of subtilisin and bacillolysin.


Covariation of Quantity and Quality of the Reinforcer in Rats.
The results of four experiments, involving the manipulation of quantity (number of pellets) and quality (caloric value of each pellet) of the reinforcer with total drive reduction held constant, are reported. Ss were female albino rats (Ns = 20, 30, 30, 20, respectively). Results in both a straight alley and T-maze situation indicated that rats (a) preferred a high quality reinforcer to a low quality reinforcer, (b) preferred a high quantity of low quality food to a low quantity of high quality food, and (c) displayed appropriate performance shifts in favoring quantity. It was concluded that the form of the reinforcer makes a difference in overall incentive value.


How I treat rare venous thromboses.
Venous thromboembolism may involve venous sites other than the lower limbs, such as cerebral, splanchnic, and upper limb veins. Although uncommon, these thromboses may be clinically severe and challenging for caregivers. In this review, the main pathogenic, clinical, and therapeutic features of thromboses in rare venous sites are discussed. Even though there was a lot of recent progress in understanding the mechanistic role of inherited and acquired thrombophilia and of the interactions between different risk factors, the optimal management of these patients is still unsettled, being currently based on the consensus of experts due to the lack of randomized trials. The implementation of large interdisciplinary registries is a necessary weapon to optimize the treatment of rare venous diseases.


Half-sib family structure of Fagus crenata saplings in an old-growth beech-dwarf bamboo forest.
Half-sib family structure of Fagus crenata saplings was examined in an old-growth beech-dwarf bamboo (Sasa spp.) forest using microsatellite genotypes in parentage analysis to identify the half-sib families in two 50 x 50 m plots: one with 36 adults, 641 saplings and no Sasa cover, the other with 21 adults, 61 saplings and Sasa cover. For large proportions of the saplings (44.6% and 75.4%, respectively) both of their parents were found within the same plot, indicating that pollination events frequently involved short-range pollen dispersal, probably because of the high density of adults in the study population. Although almost all of the adults had half-sib families, the number of offspring in the families was highly variable. In the plot with no Sasa cover, the variation in the number of offspring was significantly explained by the size of parents, i.e. the reproductive success is higher for large adults than for small adults. The half-sibs were aggregately distributed around their parents and the distribution overlapped among different half-sib families, which may be due to the limited seed dispersal and overlapping seed shadows of this species. As expected, there was weak genetic structure in the plot. By contrast, in the plot with Sasa cover, the half-sibs were distributed sparsely with a low density, and the degree of genetic structure was very weak. The difference in the half-sib family structure and genetic structure among saplings presumably reflects the difference in density that should be affected by regeneration dynamics associated with environmental conditions.


Social dominance and reproduction result in increased integration of oxidative state in males of an African cichlid fish.
Oxidative stress is a potential cost of social dominance and reproduction, which could mediate life history trade-offs between current and future reproductive fitness. However, the evidence for an oxidative cost of social dominance and reproduction is mixed, in part because organisms have efficient protective mechanisms that can counteract oxidative insults. Further, previous studies have shown that different aspects of oxidative balance, including oxidative damage and antioxidant function, vary dramatically between tissue types, yet few studies have investigated oxidative cost in terms of interconnectedness and coordination within the system. Here, we tested whether dominant and subordinate males of the cichlid Astatotilapia burtoni differ in integration of different components of oxidative stress. We assessed 7 markers of oxidative stress, which included both oxidative damage and antioxidant function in various tissue types (total of 14 measurements). Across all oxidative stress measurements, we found more co-regulated clusters in dominant males, suggesting that components of oxidative state are more functionally integrated in dominant males than they are in subordinate males. We discuss how a high degree of functional integration reflects increased robustness or efficiency of the system (e.g. increased effectiveness of antioxidant machinery in reducing oxidative damage), but we also highlight potential costs (e.g. activation of cytoprotective mechanisms may have unwanted pleiotropic effects). Overall, our results suggest that quantifying the extent of functional integration across different components of oxidative stress could reveal insights into the oxidative cost of important life history events.


Elagolix for endometriosis: all that glitters is not gold.
Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis. As the degree of ovarian suppression obtained with elagolix is dose-dependent, pain relief may be achieved by modulating the level of hypo-oestrogenism while limiting side effects. Elagolix may thus be considered a novelty in terms of its endocrine and pharmacological properties but not for its impact on the pathogenic mechanisms of endometriosis, as the target of this new drug is, yet again, alteration of the hormonal milieu. Given the oestrogen-dependent nature of endometriosis, a reduction of side effects may imply a proportionate decrease in pain relief. Furthermore, if low elagolix doses are used, ovulation is not consistently inhibited, and patients should use non-hormonal contraceptive systems and perform serial urine pregnancy tests to rule out unplanned conception during periods of treatment-induced amenorrhoea. If high elagolix doses are used to control severe pain for long periods of time, add-back therapies should be added, similar to that prescribed when using GnRH agonists. To date, the efficacy of elagolix has only been demonstrated in placebo-controlled explanatory trials. Pragmatic trials comparing elagolix with low-dose hormonal contraceptives and progestogens should be planned to verify the magnitude of the incremental benefit, if any, of this GnRH antagonist over currently used standard treatments. The price of elagolix may impact on patient adherence and, hence, on clinical effectiveness. In the USA, the manufacturer AbbVie Inc. priced elagolix (OrilissaTM) at around $10 000 a year, i.e. $845 per month. When faced with unaffordable treatments, some patients may choose to forego care. If national healthcare systems are funded by the tax payer, the approval and the use of a new costly drug to treat a chronic condition, such as endometriosis, means that some finite financial resources will be diverted from other areas, or that similar patients will not receive the same level of care. Thus, defining the overall 'value' of a new drug for endometriosis also has ethical implications, and trade-offs between health outcomes and costs should be carefully weighed up.


Somatotopic representation of hindlimb skin in cat dorsal horn.
Single-unit exploration of the dorsal horn of segments L4-S2 of unanesthetized cats with the neuraxis transected at lower thoracic levels reveals a somototopic organization in the horizontal plane. The dorsal horn dermatomes correspond closely to the dermatomes of the corresponding dorsal roots, and the ML gradient is equally well described by two different projection schemes: a distoproximal gradient and a ventrodorsal one (5, 33). There is no evidence of segmental discontinuity of the map. As is the case in other nuclear regions of the CNS, the relative area devoted to projections from the foot is disproportionately large relative to the area devoted to skin regions of similar size which are located more proximally on the limb. From our data, and from the close correspondence to anatomical data obtained by others, we suggest that at least some cutaneous afferent fibers from a given skin area project directly to any dorsal horn region where that skin area is represented. This assumption, together with the organization of the dorsal horn map, yields a model which predicts a precise somatotopic organization of presynaptic neuropil in the substantia gelatinosa.


Rapid and reliable loop-mediated isothermal amplification method for detecting Streptococcus agalactiae.
Streptococcus agalactiae (group B Streptococcus, GBS) is the leading cause of neonatal sepsis and meningitis and an important pathogen in elderly patients and those with underlying diseases. The diagnosis of GBS infections is primarily based on culture of GBS. Some clinical laboratories perform the Christie-Atkins-Munch-Peterson (CAMP) test for discrimination of GBS from other streptococci. Here, we developed a rapid GBS identification method, i.e., the loop-mediated isothermal amplification (LAMP) method for detecting the cfb gene encoding the CAMP factor. This method detected at least 4 copies of the cfb gene in GBS under isothermal conditions with in a short time (65 °C, within 90 min). No inappropriate amplification of nucleotide by this method was observed when the chromosomal DNA of 17 streptococci and enterococci species, other than GBS, were used as templates. In this investigation, we successfully developed a LAMP method for rapid and highly sensitive detection of GBS, which provides a beneficial alternative to the conventional CAMP test.


Spherical diffusion for 3D surface smoothing.
A diffusion-based approach to surface smoothing is presented. Surfaces are represented as scalar functions defined on the sphere. The approach is equivalent to Gaussian smoothing on the sphere and is computationally efficient since it does not require iterative smoothing. Furthermore, it does not suffer from the well-known shrinkage problem. Evolution of important shape features (parabolic curves) under diffusion is demonstrated. A nonlinear modification of the diffusion process is introduced in order to improve smoothing behavior of elongated and poorly centered objects.


Intralimb joint coordination patterns of the lower extremity in maximal velocity phase sprint running.
This study aimed to develop insight into the lower extremity joint coupling motions used in the maximal velocity phase of sprint running. Two-dimensional coordinate data were used to derive sagittal plane joint angle profiles of sprint running trials. Intralimb joint coupling motions were examined using a continuous relative phase (CRP) analysis. The knee-ankle (KA) coupling was more out of phase compared with the hip-knee (HK) coupling across the step phase (mean CRP: KA 89.9 degrees; HK 34.2 degrees) and produced a lower within-athlete CRP variability (VCRP) in stance. Touchdown (TD) produced more out-of-phase motions and a larger VCRP than toe-off. A destabilization of the lower extremity coordination pattern was considered necessary at TD to allow for the swing-to-stance transition. The key role that the KA joint motion has in the movement patterns used by healthy athletes in the maximal velocity phase of sprint running was highlighted.


Cytopathic effects of toxogenic strains of Helicobacter pylori on different cell lines.
Many virulence factors are involved in the pathomechanism of infection caused by Helicobacter pylori. Toxins such as vacuolating cytotoxin, encoded by the vacA gene and the immunogenic protein cagA, encoded by the cagA gene (cytotoxin-associated gene) are major factors conferring the property of virulence. The current study is aimed at isolation of H. pylori and separation of its toxin from antral biopsies of patients. The following cell lines were used to demonstrate the cytopathic effect (CPE) of the separated toxin: African green monkey kidney (Vero), baby hamster kidney, human lung carcinoma (LLC-MK2), and human epithelial. H. pylori was isolated from 27 out of 45 patients (60%) selected for the study. CPE of H. pylori toxin was highly significant on Vero cells than other cell lines used as it reached a high dilution titer of toxin (1/16) in 13 isolated strains (48.15%). No significant difference in CPE of toxin in different dilutions was detected among other cell lines used in different groups. H. pylori toxin could be detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis as a distinct band with a molecular weight ranging between 66 and 97 kDa and closely related to 87 kDa. H. pylori vacuolating cytotoxin plays a vital role in the pathogenesis of gastroduodenal diseases (gastritis, gastric ulcer, duodenal ulcer, and gastric cancer). The Vero cell lines were found to be the most suitable form of tissue culture when compared with other cell lines used in our study for demonstrating the activity of H. pylori toxin.


TCR-dependent translational control of GATA-3 enhances Th2 differentiation.
The differentiation of CD4(+) T cells into the Th2 subset is controlled by the transcription factor GATA-3. GATA-3 is both necessary and sufficient for Th2 differentiation and works through the induction of chromatin remodeling at the Th2 effector cytokine loci. We show in this study that IL-4 stimulation induces GATA-3 mRNA upregulation, but the level of GATA-3 protein induced is insufficient for Th2 differentiation. The levels of GATA-3 protein and Th2 differentiation are enhanced by concomitant TCR signaling through the PI3K/mammalian target of rapamycin pathway. The PI3K-mediated increase in GATA-3 protein occurs without increasing the GATA-3 mRNA level. Rather, TCR signaling through PI3K specifically enhances the translation rate of GATA-3 without affecting the protein stability. Importantly, this role of TCR signaling is independent of the effects of TCR signaling in T cell survival and expansion. Thus, TCR signaling through PI3K may play a critical role in Th2 differentiation by the specific enhancement of GATA-3 translation.


Finishing the egg.
Gamete development is a fundamental process that is highly conserved from early eukaryotes to mammals. As germ cells develop, they must coordinate a dynamic series of cellular processes that support growth, cell specification, patterning, the loading of maternal factors (RNAs, proteins, and nutrients), differentiation of structures to enable fertilization and ensure embryonic survival, and other processes that make a functional oocyte. To achieve these goals, germ cells integrate a complex milieu of environmental and developmental signals to produce fertilizable eggs. Over the past 50 years, Drosophila oogenesis has risen to the forefront as a system to interrogate the sophisticated mechanisms that drive oocyte development. Studies in Drosophila have defined mechanisms in germ cells that control meiosis, protect genome integrity, facilitate mRNA trafficking, and support the maternal loading of nutrients. Work in this system has provided key insights into the mechanisms that establish egg chamber polarity and patterning as well as the mechanisms that drive ovulation and egg activation. Using the power of Drosophila genetics, the field has begun to define the molecular mechanisms that coordinate environmental stresses and nutrient availability with oocyte development. Importantly, the majority of these reproductive mechanisms are highly conserved throughout evolution, and many play critical roles in the development of somatic tissues as well. In this chapter, we summarize the recent progress in several key areas that impact egg chamber development and ovulation. First, we discuss the mechanisms that drive nutrient storage and trafficking during oocyte maturation and vitellogenesis. Second, we examine the processes that regulate follicle cell patterning and how that patterning impacts the construction of the egg shell and the establishment of embryonic polarity. Finally, we examine regulatory factors that control ovulation, egg activation, and successful fertilization.


Association of asthma with osteopenia, osteoporosis, osteomalacia, and fractures.
Background: Previous studies that examined the relationship between asthma, osteoporosis, and pathologic fractures found conflicting results. Objective: To determine whether asthma is associated with osteopenia, osteoporosis, osteomalacia, and fractures in U.S. adults. Methods: A cross-sectional study of 198,102,435 children and adults, including 10,129,307 with asthma, from the 2006-2012 National Emergency Department Sample, which includes a representative 20% sample of emergency department (ED) visits throughout the United States. Results: ED visits of patients with versus without asthma were associated with higher odds of osteopenia (7 of 7 years: multivariable logistic regression of all years pooled; adjusted odds ratio [aOR] 1.45 [95% confidence interval {CI}, 1.41-1.50]), osteoporosis (7 of 7 years: aOR 1.85 [95% CI, 1.82-1.88]), osteomalacia (7 of 7 years: aOR 2.00 [95% CI, 1.61-2.49]), and pathologic fractures (7 of 7 years: OR 1.24 [95% CI, 1.20-1.27]). Patients with asthma and with long-term glucocorticoid use had higher odds of osteoporosis, osteopenia, osteomalacia, and fractures compared with patients with asthma and without long-term glucocorticoid use. Patients with asthma and with fractures incurred significantly more inpatient admissions, and higher costs of ED and inpatient care. Conclusion: ED visits with asthma were associated with osteopenia, osteoporosis, osteomalacia, and pathologic fractures.


Replication properties of clade A/C chimeric feline immunodeficiency viruses and evaluation of infection kinetics in the domestic cat.
Feline immunodeficiency virus (FIV) causes progressive immunodeficiency in domestic cats, with clinical course dependent on virus strain. For example, clade A FIV-PPR is predominantly neurotropic and causes a mild disease in the periphery, whereas clade C FIV-C36 causes fulminant disease with CD4(+) T-cell depletion and neutropenia but no significant pathology in the central nervous system. In order to map pathogenic determinants, chimeric viruses were prepared between FIV-C36 and FIV-PPR, with reciprocal exchanges involving (i) the 3' halves of the viruses, including the Vif, OrfA, and Env genes; (ii) the 5' end extending from the 5' long terminal repeat (LTR) to the beginning of the capsid (CA)-coding region; and (iii) the 3' LTR and Rev2-coding regions. Ex vivo replication rates and in vivo replication and pathologies were then assessed and compared to those of the parental viruses. The results show that FIV-C36 replicates ex vivo and in vivo to levels approximately 20-fold greater than those of FIV-PPR. None of the chimeric FIVs recapitulated the replication rate of FIV-C36, although most replicated to levels similar to those of FIV-PPR. The rates of chloramphenicol acetyltransferase gene transcription driven by the FIV-C36 and FIV-PPR LTRs were identical. Furthermore, the ratios of surface glycoprotein (SU) to capsid protein (CA) in the released particles were essentially the same in the wild-type and chimeric FIVs. Tests were performed in vivo on the wild-type FIVs and chimeras carrying the 3' half of FIV-C36 or the 3' LTR and Rev2 regions of FIV-C36 on the PPR background. Both chimeras were infectious in vivo, although replication levels were lower than for the parental viruses. The chimera carrying the 3' half of FIV-C36 demonstrated an intermediate disease course with a delayed peak viral load but ultimately resulted in significant reductions in neutrophil and CD4(+) T cells, suggesting potential adaptation in vivo. Taken together, the findings suggest that the rapid-growth phenotype and pathogenicity of FIV-C36 are the result of evolutionary fine tuning throughout the viral genome, rather than being properties of any one constituent.


Effects of triple therapy with octreotide, galanin and serotonin on a human colon cancer cell line implanted in mice: comparison between different routes of administration.
A human colon cancer cell line was implanted subcutaneously in nude mice. After 7 days, the animals were divided into four groups. The first group received an intraperitoneal (i.p.) continuous infusion by an osmotic pump, the second was given i.p. bolus injections, the third received continuous subcutaneous (s.c.) infusion by an osmotic pump and the fourth group was given bolus s.c. injections. Each group was divided into 2 subgroups. The first subgroup received triple treatment with octreotide, galanin, and serotonin, 40 microg/kg body weight/day of each. The second subgroup was given sterile saline solution. Treatment lasted for 14 days. The volume and wet weight of the tumours in all treated groups tended to decrease, but was statistically significant only in the group with continuous i.p. infusion. The number of viable cells tended to decrease in all the treated groups, but was not statistically significant. Proliferation index was significantly reduced in mice given triple therapy i.p. as bolus injection and as continuous infusion, as compared with their respective controls. The apoptotic index increased significantly in mice receiving triple therapy as continuous i.p. infusion as revealed by both the TUNEL method and by poly (ADP-ribose) polymerase (PARP) expression. The number of tumour blood vessels was significantly reduced in the mice given triple therapy as continuous i.p. infusion, as compared with controls. There was no statistical difference between animals treated by different routes, regarding proliferation or apoptosis of the cancer cells, or the number or mean luminal area of tumour blood vessels. The present investigation showed that regardless of the route of administration, triple therapy with octreotide, galanin and serotonin generally reduced the volumes, weights, viable cells, vascularization and proliferation of the tumours, as well as inducing apoptosis. Continuous i.p. infusion appears, however, to be the most effective route of administration.


Advances in the pharmacotherapy of chronic heart failure with preserved ejection fraction: an ideal opportunity for precision medicine.
Heart failure with preserved ejection fraction (HFpEF), which comprises approximately 50% of all heart failure patients, is a challenging and complex clinical syndrome that is often thought to lack effective treatments. Areas covered: Despite the common mantra that HFpEF has no effective treatments, closer inspection of HFpEF clinical trials reveals that several of the drugs tested are associated with benefits in exercise capacity and quality of life, and reduction in heart failure hospitalization. Here we review major randomized controlled trials in HFpEF, focusing on renin-angiotensin-aldosterone system antagonists, organic nitrates, digoxin, beta-blockers, and phosphodiesterase-5 inhibitors. In addition, we review several classes of drugs currently in development for HFpEF such as neprilysin inhibitors, inorganic nitrates (nitrites), and soluble guanylate cyclase stimulators. Expert opinion: HFpEF should not be viewed as lacking effective treatments. While there have been no breakthrough clinical trials showing a reduction in mortality, several existing medications are likely to benefit specific subgroups of HFpEF patients. HFpEF is now well known to be a heterogeneous syndrome; thus, the clinical management of HFpEF patients and future HFpEF clinical trials will both likely require a nuanced, phenotype-specific approach instead of a one-size-fits-all tactic. Drug development for HFpEF therefore represents an exciting opportunity for personalized medicine.


Reservoir role of lizard Psammodromus algirus in transmission cycle of Borrelia burgdorferi sensu lato (Spirochaetaceae) in Tunisia.
To investigate the reservoir role of the lizard Psammodromus algirus for the Lyme disease spirochete, 199 lizards were trapped from April to October 2003 in El Jouza, northwestern Tunisia. In this site, the infection rate of free-living Ixodes ricinus (L.) by Borrelia was evaluated by immunofluorescence as 34.6% for adult ticks and 12.5% for nymphs. Eighty percent of P. algirus (117/146) captured during this study were infested by I. ricinus, the predominant tick species collected from lizards. The intensity of tick infestation of this host by larvae and nymphs ranged from 0.14 to 7.07 and from 1.5 to 6.58, respectively. These immature stages of I. ricinus were found on lizards in spring and the beginning of summer, with a peak of intensity during June (10.16 immature ticks by lizard). Tissue cultures from lizards and xenodiagnosis with larval I. ricinus were used to assess the infection and the ability, respectively, of infected lizards to transmit Borrelia to naive ticks. Seventeen percent of xenodiagnostic ticks (40/229) acquired B. lusitaniae while feeding on P. algirus. Therefore, we demonstrated the ability of the lizards to sustain Borrelia infection and to infect attached ticks, and we proved that P. algirus is a reservoir host competent to transmit B. lusitaniae.


Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin.
Background: Our previous work determined the correlation between high nuclear expression of hepatoma-derived growth factor (HDGF) and clinicopathological data of endometrial cancer (EC); however, the modulatory mechanisms and biological role of HDGF in EC have not been reported. Methods: Lentiviral particles carrying human HDGF short hairpin RNA (shHDGF-1, -2, and -3) vector and plasmids for HDGF, DDX5, and β-catenin expression were, respectively introduced into EC cells to evaluate the effects and molecular mechanisms underlying EC cell proliferation, migration, invasion, and metastasis. Quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were used to determine HDGF and DDX5 expression. Co-immunoprecipitation (co-IP), mass spectrometry, and an immunofluorescence co-localization study were conducted to explore the relationship between HDGF, DDX5, and β-catenin. Immunohistochemistry was used to analyze the clinical associations between HDGF and DDX5 in EC. Results: Knocking down HDGF expression significantly decreased EC cellular proliferation, migration, invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, HDGF overexpression reversed these effects. Stable knockdown-based HDGF suppression activated the PI3K/AKT signaling pathway, along with downstream β-catenin-mediated cell cycle and epithelial-mesenchymal transition signaling. Furthermore, co-IP combined with mass spectrometry and an immunofluorescence co-localization study indicated that HDGF interacts with DDX5, whereas β-catenin was associated with DDX5 but not HDGF. Overexpression of DDX5 reversed the suppression of shHDGF. Immunohistochemistry analysis showed that high expression of DDX5 constituted an unfavorable factor with respect to the clinicopathological characteristics of EC tissues and that HDGF and DDX5 high expression (HDGF+/DDX5+) led to a worse prognosis for patients with EC (P < 0.001). In addition, we found that the expression of HDGF and DDX5 was positively correlated in EC tissues (r = 0.475, P < 0.001). Conclusion: Our results provide novel evidence that HDGF interacts with DDX5 and promotes the progression of EC through the induction of β-catenin.


Reticular Chemistry for Optical Sensing of Anions.
In the last few decades, reticular chemistry has grown significantly as a field of porous crystalline molecular materials. Scientists have attempted to create the ideal platform for analyzing distinct anions based on optical sensing techniques (chromogenic and fluorogenic) by assembling different metal-containing units with suitable organic linking molecules and different organic molecules to produce crystalline porous materials. This study presents novel platforms for anion recognition based on reticular chemistry with high selectivity, sensitivity, electronic tunability, structural recognition, strong emission, and thermal and chemical stability. The key materials for reticular chemistry, Metal-Organic Frameworks (MOFs), Zeolitic Imidazolate Frameworks (ZIFs), and Covalent-Organic Frameworks (COFs), and the pre- and post-synthetic modification of the linkers and the metal oxide clusters for the selective detection of the anions, have been discussed. The mechanisms involved in sensing are also discussed.


Estimates of pandemic influenza vaccine effectiveness in Europe, 2009-2010: results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) multicentre case-control study.
A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009-2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1). Sentinel practitioners swabbed ILI patients using systematic sampling. We included in the study patients meeting the European ILI case definition with onset of symptoms >14 days after the start of national pandemic vaccination campaigns. We compared pH1N1 cases to influenza laboratory-negative controls. A valid vaccination corresponded to >14 days between receiving a dose of vaccine and symptom onset. We estimated pooled vaccine effectiveness (VE) as 1 minus the odds ratio with the study site as a fixed effect. Using logistic regression, we adjusted VE for potential confounding factors (age group, sex, month of onset, chronic diseases and related hospitalizations, smoking history, seasonal influenza vaccinations, practitioner visits in previous year). We conducted a complete case analysis excluding individuals with missing values and a multiple multivariate imputation to estimate missing values. The multivariate imputation (n = 2902) adjusted pandemic VE (PIVE) estimates were 71.9% (95% confidence interval [CI] 45.6-85.5) overall; 78.4% (95% CI 54.4-89.8) in patients <65 years; and 72.9% (95% CI 39.8-87.8) in individuals without chronic disease. The complete case (n = 1,502) adjusted PIVE were 66.0% (95% CI 23.9-84.8), 71.3% (95% CI 29.1-88.4), and 70.2% (95% CI 19.4-89.0), respectively. The adjusted PIVE was 66.0% (95% CI -69.9 to 93.2) if vaccinated 8-14 days before ILI onset. The adjusted 2009-2010 seasonal influenza VE was 9.9% (95% CI -65.2 to 50.9). Our results suggest good protection of the pandemic monovalent vaccine against medically attended pH1N1 and no effect of the 2009-2010 seasonal influenza vaccine. However, the late availability of the pandemic vaccine and subsequent limited coverage with this vaccine hampered our ability to study vaccine benefits during the outbreak period. Future studies should include estimation of the effectiveness of the new trivalent vaccine in the upcoming 2010-2011 season, when vaccination will occur before the influenza season starts.


Stem Design in Total Hip Arthroplasty Influences Ipsilateral Knee Valgus: A Retrospective Comparative Analysis of 2953 Cases.
Total hip arthroplasty (THA) affects the biomechanics of the hip and the patient gait. The stem design influences femoral lever ratios and tissue trauma. Biomechanical changes such as these have the potential to induce knee arthritis. A varus or valgus configuration of knee arthritis is formed by asymmetric loadings. The aim of this study was to evaluate the impact of stem design in THA on knee valgus by comparing a standard implant with an implant with a short stem. A total of 2953 patients who underwent primary total knee arthroplasty for end-stage osteoarthritis between 2015 and 2021 were included in this retrospective data analysis. Patients were divided into three groups, depending on hip status (straight stem, short stem, and native joint). Leg alignment was distinguished as varus or valgus, and the degree of axial deviation was measured. Descriptive and explorative statistical analyses were performed, with a p value < 0.05 set as significant. Ipsilateral knee valgus occurred significantly more often in patients with straight stems (57.2%) than in those with short stems (29%) and native joints (25.8%) (p < 0.001). Additionally, mean valgus deviation was significantly increased in patients with straight stems (8.9°) compared to those with short stems (6.4°) or native hip joints (6.7°). Both findings were accentuated in women. Previous ipsilateral straight-stem THA is associated with knee valgus deformity, especially in women. Short-stem THA seems to be better suited to restoring physiological biomechanics and preventing the development of valgus osteoarthritis of the ipsilateral knee.


Latent transition models with latent class predictors: attention deficit hyperactivity disorder subtypes and high school marijuana use.
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder which is most often diagnosed in childhood with symptoms often persisting into adulthood. Elevated rates of substance use disorders have been evidenced among those with ADHD, but recent research focusing on the relationship between subtypes of ADHD and specific drugs is inconsistent. We propose a latent transition model (LTM) to guide our understanding of how drug use progresses, in particular marijuana use, while accounting for the measurement error that is often found in self-reported substance use data. We extend the LTM to include a latent class predictor to represent empirically derived ADHD subtypes that do not rely on meeting specific diagnostic criteria. We begin by fitting two separate latent class analysis (LCA) models by using second-order estimating equations: a longitudinal LCA model to define stages of marijuana use, and a cross-sectional LCA model to define ADHD subtypes. The LTM model parameters describing the probability of transitioning between the LCA-defined stages of marijuana use and the influence of the LCA-defined ADHD subtypes on these transition rates are then estimated by using a set of first-order estimating equations given the LCA parameter estimates. A robust estimate of the LTM parameter variance that accounts for the variation due to the estimation of the two sets of LCA parameters is proposed. Solving three sets of estimating equations enables us to determine the underlying latent class structures independently of the model for the transition rates and simplifying assumptions about the correlation structure at each stage reduces the computational complexity.


[Diagnostic sensitivity of sonography in varicose and post-thrombotic venous insufficiency].
We report on the application possibilities of sonography in phlebology. Sonographic examination of 131 lower legs showing various clinical forms of chronic venous insufficiency is discussed. Ultrasound offers a timesaving, non-invasive, and reproducible technique to detect insufficiencies concerning orifice or trunk of the great and lower saphenous veins as well as the perforating veins. The method allows varying diagnostic sensitivities. Thrombotic changes in the deep veins may be demonstrated with relative accurateness. As to insufficiencies concerning the epifascial and perforating venous system (in epifascial chronic venous insufficiency, stage I to IV), the question of surgical or sclerotherapeutic treatment can be settled in most cases according to the sonographical findings alone. Subfascial forms of chronic venous insufficiency require additional invasive diagnostic techniques, such as plethysmography, phlebography, and venous pressure measurements. In consideration of the high diagnostic importance of ultrasound, sonographic devices should be available and applied in a large number of phlebologic practices.


Darwinian Dynamics of Intratumoral Heterogeneity: Not Solely Random Mutations but Also Variable Environmental Selection Forces.
Spatial heterogeneity in tumors is generally thought to result from branching clonal evolution driven by random mutations that accumulate during tumor development. However, this concept rests on the implicit assumption that cancer cells never evolve to a fitness maximum because they can always acquire mutations that increase proliferative capacity. In this study, we investigated the validity of this assumption. Using evolutionary game theory, we demonstrate that local cancer cell populations will rapidly converge to the fittest phenotype given a stable environment. In such settings, cellular spatial heterogeneity in a tumor will be largely governed by regional variations in environmental conditions, for example, alterations in blood flow. Model simulations specifically predict a common spatial pattern in which cancer cells at the tumor-host interface exhibit invasion-promoting, rapidly proliferating phenotypic properties, whereas cells in the tumor core maximize their population density by promoting supportive tissue infrastructures, for example, to promote angiogenesis. We tested model predictions through detailed quantitative image analysis of phenotypic spatial distribution in histologic sections of 10 patients with stage 2 invasive breast cancers. CAIX, GLUT1, and Ki67 were upregulated in the tumor edge, consistent with an acid-producing invasive, proliferative phenotype. Cells in the tumor core were 20% denser than the edge, exhibiting upregulation of CAXII, HIF-1α, and cleaved caspase-3, consistent with a more static and less proliferative phenotype. Similarly, vascularity was consistently lower in the tumor center compared with the tumor edges. Lymphocytic immune responses to tumor antigens also trended to higher level in the tumor edge, although this effect did not reach statistical significance. Like invasive species in nature, cancer cells at the leading edge of the tumor possess a different phenotype from cells in the tumor core. Our results suggest that at least some of the molecular heterogeneity in cancer cells in tumors is governed by predictable regional variations in environmental selection forces, arguing against the assumption that cancer cells can evolve toward a local fitness maximum by random accumulation of mutations. Cancer Res; 76(11); 3136-44. ©2016 AACR.


[Treatment of skin lesions combining hydrofiber and extra-fine hydrochloride dressings].
Multicentric trial to test the efficacy of the combined use of two hydrocolloid dressings (AQUACEL + Varihesive Extra Fino) or a hydrocolloid dressing and gauze in the treatment of different aetiology lesions. Includes 1,805 patients with lesions that can be treated with the cure system under study, without wound dimensions or severity restrictions. At the end of the trial period, 78.3% of the lesions reached healing or a significant improvement of their condition, resulting in an increase of patients' quality of life. 90% of patients confirmed their willingness to continue the treatment with AQUACEL.


Frequency and characteristics of spinal bleeding sources in non-traumatic angiogram-negative subarachnoid hemorrhage.
Angiogram-negative subarachnoid hemorrhage (AN-SAH) accounts for 5-15% of spontaneous SAH. This study aims to analyze the frequency and characteristics of spinal bleeding sources in patients with AN-SAH. 140 patients suffering from AN-SAH treated at our institution from 2012 to 2022 were included in this retrospective cohort study. 52.1% were diagnosed with perimesencephalic SAH, 35.0% with non-perimesencephalic SAH and 12.9% with CT-negative SAH (diagnosed by lumbar puncture). Additional MRI identified a spinal bleeding source in 4 patients (2.86%). These patients presented with local spine pain or neurological deficits (RR 3.9706 [95%-CI: 0.7272-21.6792]; p<0.001) and were younger (mean difference 14.85 years [95%-CI: 0.85-28.85; p=0.038]) compared to patients without a spinal bleeding source. AN-SAH caused by spinal pathology is rare. This study indicates that craniocervical and holospinal MRI should be considered in AN-SAH, especially for young patients with AN-SAH who present with back pain or neurological deficits.


Objective quality assessment of MPEG-2 video streams by using CBP neural networks.
The increasing use of compression standards in broadcasting digital TV has raised the need for established criteria to measure perceived quality. Novel methods must take into account the specific artifacts introduced by digital compression techniques. This paper presents a methodology using circular backpropagation (CBP) neural networks for the objective quality assessment of motion picture expert group (MPEG) video streams. Objective features are continuously extracted from compressed video streams on a frame-by-frame basis; they feed the CBP network estimating the corresponding perceived quality. The resulting adaptive modeling of subjective perception supports a real-time system for monitoring displayed video quality. The overall system mimics perception but does not require an analytical model of the underlying physical phenomenon. The ability to process compressed video streams represents a crucial advantage over existing approaches, as avoiding the decoding process greatly enhances the system's real-time performance. Experimental evidence confirmed the approach validity. The system was tested on real test videos; they included different contents ranging from fiction to sport. The neural model provided a satisfactory, continuous-time approximation for actual scoring curves, which was validated statistically in terms of confidence analysis. As expected, videos with slow-varying contents such as fiction featured the best performances.


Alzheimer-signature MRI biomarker predicts AD dementia in cognitively normal adults.
Since Alzheimer disease (AD) neuropathology is thought to develop years before dementia, it may be possible to detect subtle AD-related atrophy in preclinical AD. Here we hypothesized that the "disease signature" of AD-related cortical thinning, previously identified in patients with mild AD dementia, would be useful as a biomarker to detect anatomic abnormalities consistent with AD in cognitively normal (CN) adults who develop AD dementia after longitudinal follow-up. We studied 2 independent samples of adults who were CN when scanned. In sample 1, 8 individuals developing AD dementia (CN-AD converters) after an average of 11.1 years were compared to 25 individuals who remained CN (CN-stable). In sample 2, 7 CN-AD converters (average follow-up 7.1 years) were compared to 25 CN-stable individuals. AD-signature cortical thinning in CN-AD converters in both samples was remarkably similar, about 0.2 mm (p < 0.05). Despite this small absolute difference, Cohen d effect sizes for these differences were very large (> 1). Of the 11 CN individuals with baseline low AD-signature thickness (≥ 1 SD below cohort mean), 55% developed AD dementia over nearly the next decade, while none of the 9 high AD-signature thickness individuals (≥ 1 SD above mean) developed dementia. This marker predicted time to diagnosis of dementia (hazard ratio = 3.4, p < 0.0005); 1 SD of thinning increased dementia risk by 3.4. By focusing on cortical regions known to be affected in AD dementia, subtle but reliable atrophy is identifiable in asymptomatic individuals nearly a decade before dementia, making this measure a potentially important imaging biomarker of early neurodegeneration.


Simultaneous occurrence of ETV6-RUNX1 and BCR-ABL1 (e1a2) transcripts in a child with B-cell acute lymphoblastic leukemia.
We report on a rare case of a 3-year-old boy with B-cell acute lymphoblastic leukemia (B-ALL), which was characterized simultaneously with two different fusion transcripts: ETV6-RUNX1 and BCR-ABL1 (e1a2). The patient presented with fever, diarrhea, normal white blood cell counts of 5.9×10(9)/L without circulating abnormal cells, anemia, and thrombocytopenia, as well as an enlarged liver without splenomegaly. The bone marrow was markedly hypercellular with a total infiltration of agranular lymphoid blast cells with a B-II (pre-B) lymphoblastic phenotype: cyCD79α(+), CD19(+), sCD22(+), CD10(+), CD20(-), CD34(+), and sIgM(-), with dim aberrant co-expression of the myeloid-associated markers CD13(+) and CD33(+). Conventional cytogenetic analysis was unsuccessful; however, molecular analysis revealed the BCR-ABL1 (p190) and ETV6-RUNX1 transcripts. A diagnosis of BCR-ABL1 (p190)-positive and ETV6-RUNX1-positive B-ALL was made, and treatment was initiated according to the AIEOP-BFM-ALL2000 protocol. A complete remission was achieved after the first induction course of chemotherapy. Twelve months after the diagnosis, the child is alive with levels of residual disease of <0.05% estimated both by 8-color flow cytometry and real-time quantitative reverse transcription polymerase chain reaction.


Effects of theanine on alcohol metabolism and hepatic toxicity.
We previously showed that theanine, is a major amino acid in green tea, enhanced doxorubicin (DOX) induced antitumor activity. Besides, theanine induced the elevation of glutathione (GSH) level attributable to the increase of glutamate in the liver of mice, namely theanine would reduce the adverse reaction of DOX. Consequently, theanine was thought to be effective against the tissue changes with GSH level reduction. On the other hand, it is suggested excessive uptake of alcohol causes a production of free radicals, a decrease of GSH level, and an increase in the amount of lipid peroxide (LPO) in liver, and shifting to an alcoholic liver injury. Then, aiming at the prevention and medical treatment of a hepatic toxicity by the food components with little toxicity, we have studied the effect of theanine (i.p.) on ethanol metabolism and hepatic toxicity using ethanol (p.o.) single-administered mice. On the 1st hour after ethanol administration, the ethanol concentrations in blood of the theanine combined groups decreased compared with the ethanol-alone group. The alcohol dehydrogenase and aldehyde dehydrogenase activities in the liver increased by combined theanine. Since the elevation of cytochrome P450 (CYP) 2E1 activity was controlled in the theanine-combined groups, it was considered that these disorders attributable to CYP2E1 in ethanol long-term uptake might be avoidable by theanine. Although LPO increased in 3 h after by single-administration of ethanol, the increase was controlled by theanine-administration and was improved until the normal level. In conclusion, it was indicated that theanine was effective against alcoholic liver injury.


Mechanical and structural comparison between primary tumor and lymph node metastasis cells in colorectal cancer.
SW480 and SW620 colon carcinoma cell lines derive from primary tumour and lymph-node metastasis of the same patient, respectively. For this reason, these cells represent an ideal system to analyse phenotypic variations associated with the metastatic process. In this study we analysed SW480 and SW620 cytoskeleton remodelling by measuring the cells' mechanics and morphological properties using different microscopic techniques. We observed that different specialized functions of cells, i.e. the capacity to metastasize of elongated cells inside the primary tumour and the ability to intravasate and resist shear forces of the stream of cells derived from lymph node metastasis, are reflected in their mechanical properties. We demonstrated that, together with stiffness and adhesion between the AFM tip and the cell surface, cell shape, actin organization and surface roughness are strictly related and are finely modulated by colorectal cancer cells to better accomplish their specific tasks in cancer growth and invasion.


Production of constitutively acetylated recombinant p53 from yeast and Escherichia coli by tethered catalysis.
Post-translational modification of proteins is a dynamic way of generating new protein-protein interaction interfaces that are critical for signaling networks in diverse cellular functions. Purified recombinant proteins frequently lack these signature modifications. Using the tumor suppressor p53 as the model protein, we present here a tethered catalysis approach for the production of acetylated p53 in vivo. P53 is a major tumor suppressor protein that protects the cell from various oncogenic stresses. Upon DNA damage, p53 is stabilized and activated by a plethora of post-translational modifications, including acetylation. Here, we show that constitutively acetylated p53 can be expressed and purified from both yeast and Escherichia coli. This method is highly suitable for studying protein-protein interactions in the conventional yeast two-hybrid screen that requires a constitutively acetylated state of p53. Furthermore, effective production and purification of acetylated p53 from E. coli supports future biochemical and structural characterization. The method described in this work can be applied to other proteins and modifications, and thus has widespread use in the fields of signal transduction and proteomic research.


A theoretical study on surfactant adsorption kinetics: effect of bubble shape on dynamic surface tension.
A planar or spherical fluid-liquid interface was commonly assumed on studying the surfactant adsorption kinetics for a pendant bubble in surfactant solutions. However, the shape of a pendant bubble deviates from a sphere unless the bubble's capillary constant is close to zero. Up to date, the literature has no report about the shape effect on the relaxation of surface tension due to the shape difference between a pendant bubble and a sphere. The dynamic surface tension (DST), based on the actual shape of a pendant bubble with a needle, of the diffusion-controlled process is simulated using a time-dependent finite element method in this work. The shape effect and the existence of a needle on DST are investigated. This numerical simulation resolves also the time-dependent bulk surfactant concentration. The depth of solution needed to satisfy the classical Ward-Tordai infinite-solution assumption was also studied. For a diffusion-controlled adsorption process, bubble shape and needle size are two major factors affecting the DST. The existence of a needle accelerates the bulk diffusion for a small bubble; however, the shape of a large pendant bubble decelerates the bulk diffusion. An example using this method on the DST data of C12E4 is illustrated at the end of this work.


Prenatal diagnosis of Hartsfield syndrome with a novel genetic variant.
A G2P0, 24-year-old woman presented at 17 weeks 3 days gestation for a fetal anatomy scan. Ultrasound identified bilateral upper and lower extremity ectrodactyly, semilobar holoprosencephaly, midface hypoplasia, and cleft lip and palate. Amniocentesis for a chromosome microarray demonstrated no significant copy number changes. Whole exome sequencing was subsequently completed, which revealed a de novo, likely pathogenic variant in FGFR1, c.2044G>A (D682N), consistent with FGFR1-related Hartsfield syndrome. This case highlights the first presumed molecularly confirmed prenatal diagnosis of Hartsfield syndrome and identifies a new pathogenic variant.


Assembly of the non-heading pak choi genome and comparison with the genomes of heading Chinese cabbage and the oilseed yellow sarson.
Brassica rapa displays a wide range of morphological diversity which is exploited for a variety of food crops. Here we present a high-quality genome assembly for pak choi (Brassica rapa L. subsp. chinensis), an important non-heading leafy vegetable, and comparison with the genomes of heading type Chinese cabbage and the oilseed form, yellow sarson. Gene presence-absence variation (PAV) and genomic structural variations (SV) were identified, together with single nucleotide polymorphisms (SNPs). The structure and expression of genes for leaf morphology and flowering were compared between the three morphotypes revealing candidate genes for these traits in B. rapa. The pak choi genome assembly and its comparison with other B. rapa genome assemblies provides a valuable resource for the genetic improvement of this important vegetable crop and as a model to understand the diversity of morphological variation across Brassica species.


Outcome after reinfection following reimplantation hip arthroplasty.
Between 1976 and 1992, reinfection developed in 34 patients treated for an infected total hip arthroplasty with removal of the prosthesis and implantation of another prosthesis. These patients included 15 men and 19 women with a mean age of 62 years. Infection recurred an average of 2.2 years after reimplantation of the new prosthesis. Followup after the diagnosis of reinfection averaged 5.1 years. Reinfection after an attempt at reimplantation total hip arthroplasty was seldom compatible with a good functional outcome. Resection arthroplasty was reliable in eradicating reinfection but led to poor function and was associated with persistent pain. Although reimplantation of a third prosthesis allowed 3 patients to achieve an excellent result, the 8 hips that failed a third reimplantation attempt had the worst functional results in this study. The results from the present series suggest that reinfection after an attempt at reimplantation is a contraindication to further attempts at a 1-stage reimplantation of another prosthesis. Those patients in whom the same single microorganism has been identified from the failed primary total hip and from the failed first reimplantation, however, may be reasonable candidates for an attempt at a 2-stage reimplantation of a third prosthesis, particularly when a deficiency in prior antibiotic therapy or surgical technique can be identified.


Trends in esophageal cancer incidence by histology, United States, 1998-2003.
Esophageal adenocarcinoma rates may be increasing, whereas, squamous cell carcinoma rates appear to be decreasing in the United States. Previous population-based research on esophageal cancer has only covered up to 68% of the country. Additional, updated research on a larger percentage of the country is needed to describe racial, ethnic and regional trends in histologic subtypes of esophageal cancer. Invasive esophageal cancer cases diagnosed between 1998 and 2003 (n = 65,926), collected by the National Program of Cancer Registries or the Surveillance, Epidemiology, and End Results program, were included. These data cover 83% of the US population. Esophageal squamous cell carcinoma incidence fell by 3.6%/year, whereas esophageal adenocarcinoma increased by 2.1%/year. Squamous cell carcinoma rates decreased among both sexes in most racial or ethnic groups, whereas adenocarcinoma rates increased primarily among white or non-Hispanic men. Except for white or non-Hispanic men, squamous cell carcinoma rates were similar to, or greater than, adenocarcinoma rates for men and women of all other races and ethnicities. The largest decrease in squamous cell carcinoma rates occurred in the West census region, which also exhibited no increase in adenocarcinoma rates. The rate of regional and distant-staged adenocarcinomas increased, while rates for local-staged adenocarcinoma remained stable. This is the first article to characterize esophageal cancer trends using data covering the majority of the US. Substantial racial, ethnic and regional variation in esophageal cancer is present in the US. Our work may inform interventions related to tobacco and alcohol use, and overweight/obesity prevention, and provide avenues for further research.


New Zealand supereruption provides time marker for the Last Glacial Maximum in Antarctica.
Multiple, independent time markers are essential to correlate sediment and ice cores from the terrestrial, marine and glacial realms. These records constrain global paleoclimate reconstructions and inform future climate change scenarios. In the Northern Hemisphere, sub-visible layers of volcanic ash (cryptotephra) are valuable time markers due to their widespread dispersal and unique geochemical fingerprints. However, cryptotephra are not as widely identified in the Southern Hemisphere, leaving a gap in the climate record, particularly during the Last Glacial Maximum (LGM). Here we report the first identification of New Zealand volcanic ash in Antarctic ice. The Oruanui supereruption from Taupo volcano (25,580 ± 258 cal. a BP) provides a key time marker for the LGM in the New Zealand sector of the SW Pacific. This finding provides a high-precision chronological link to mid-latitude terrestrial and marine sites, and sheds light on the long-distance transport of tephra in the Southern Hemisphere. As occurred after identification of the Alaskan White River Ash in northern Europe, recognition of ash from the Oruanui eruption in Antarctica dramatically increases the reach and value of tephrochronology, providing links among climate records in widely different geographic areas and depositional environments.


Omphalocele in Finland from 1993 to 2014: Trends, Prevalence, Mortality, and Associated Malformations-A Population-Based Study.
The aim of this study is to assess the changes in prevalence, mortality and termination pregnancy of omphalocele, and to identify associated anomalies. A population-based nationwide register study. All cases with omphalocele were identified in the Finnish Register of Congenital Malformations and the Care Register for Health Care from 1993 to 2014 including live births, stillbirths, and terminations of pregnancy due to fetal anomalies. Associated anomalies were recorded and analyzed, and perinatal and infant mortality and prevalence were calculated. There were 600 cases with omphalocele including 229 live births, 39 stillbirths, and 332 (55%) abortions. Birth prevalence in Finland was 1.96 per 10,000 births with no consistent trend over time. However, total prevalence was much higher (4.71/10,000) because more than half of these families chose option for the termination of pregnancy. Omphalocele is often complicated with other anomalies; most commonly chromosomal abnormalities (9.3%), heart defects (6.3%), central nervous system anomalies (3.0%), gastrointestinal, and urogenital malformations (both 2.0%). Proportion of chromosomal and central nervous system abnormalities were even higher in terminated pregnancies. Overall infant mortality was 22%. Total 1-year survival rates for isolated omphalocele, cases with multiple anomalies and neonates with chromosomal defects were 80, 88, and 17%, respectively. Omphalocele is a rare congenital anomaly, often associated with other malformations. Our data suggest that isolated cases may be more common than previously thought. In the absence of chromosomal defects, survival is reasonably good. Regardless, more than half of these pregnancies are often terminated.


Intrapleural chemotherapy with cisplatin and cytarabine in the management of malignant pleural effusion.
The purpose of this study was to evaluate the efficacy of intrapleural chemotherapy (IPC) with cisplatin and cytarabine in the management of malignant pleural effusion (MPE) from non-small-cell lung cancer (NSCLC). A prospective analysis was carried out on 40 patients with pathologically proven MPE from NSCLC who had received IPC. A single dose of cisplatin 100 mg/m(2) plus cytarabine 1200 mg/m(2) in 250 ml normal saline was instilled into the pleural space via a chest tube and drained 4 hours later. Patients were evaluated for toxicities and responses at 1, 2, & 3 weeks and then at monthly intervals if possible. Systemic chemotherapy was administered, if the patient agreed to receive it, after achieving complete control (CC) of MPE. The median duration of chest tube insertion for drainage was 7 (3 approximately 32) days. Among the assessable 37 patients, CC and partial control (PC) were 32 (86.5%) and 4 (10.8%) patients, respectively (overall response rate 97.3%). The median duration of response was 12 months (2 approximately 23) and there were only two relapses of IPC after achieving CC. Among the 35 patients who were assessable until they died, 28 patients (80.0%) maintained CC until the last follow-up. There was only one toxic death and the toxicities of IPC, versus the results obtained, were deemed acceptable. The procedures were tolerable to the patients and chemotherapy-induced complications were at an acceptable level. The outcome of this trial indicates that IPC has a superior and long lasting treatment response in the management of patients with MPE from NSCLC.


Stereological and Morphometric Analysis of MRI Chiari Malformation Type-1.
In this study, we aimed to investigate the underlying ethiological factors in chiari malformation (CM) type-I (CMI) via performing volumetric and morphometric length-angle measurements. A total of 66 individuals [33 patients (20-65 years) with CMI and 33 control subjects] were included in this study. In sagittal MR images, tonsillar herniation length and concurrent anomalies were evaluated. Supratentorial, infratentorial, and total intracranial volumes were measured using Cavalieri method. Various cranial distances and angles were used to evaluate the platybasia and posterior cranial fossa (PCF) development. Tonsillar herniation length was measured 9.09±3.39 mm below foramen magnum in CM group. Tonsillar herniation/concurrent syringomyelia, concavity/defect of clivus, herniation of bulbus and fourth ventricle, basilar invagination and craniovertebral junction abnormality rates were 30.3, 27, 18, 2, 3, and 3 percent, respectively. Absence of cisterna magna was encountered in 87.9% of the patients. Total, IT and ST volumes and distance between Chamberlain line and tip of dens axis, Klaus index, clivus length, distance between internal occipital protuberance and opisthion were significantly decreased in patient group. Also in patient group, it was found that Welcher basal angle/Boogard angle increased and tentorial slope angle decreased. Mean cranial volume and length-angle measurement values significantly decreased and there was a congenital abnormality association in nearly 81.5 percent of the CM cases. As a result, it was concluded that CM ethiology can be attributed to multifactorial causes. Moreover, congenital defects can also give rise to this condition.


[Immunotherapy with BCG in pulmonary tumors].
Results obtained with immunotherapy in 318 cases of lung cancer showed that an initial Tine test is useful prognostically (initial negativity is equivalent to poor survival), and survival increases and decreases in function of positivity and negativity respectively. The soundness of immunotherapy is borne out by the survival data.


Early Detection of Human Decision-Making in Concealed Object Visual Searching Tasks: An EEG-BiLSTM Study.
Detecting concealed objects presents a significant challenge for human and artificial intelligent systems. Detecting concealed objects task necessitates a high level of human attention and cognitive effort to complete the task successfully. Thus, in this study, we use concealed objects as stimuli for our decision-making experimental paradigms to quantify participants' decision-making performance. We applied a deep learning model, Bi-directional Long Short Term Memory (BiLSTM), to predict the participant's decision accuracy by using their electroencephalogram (EEG) signals as input. The classifier model demonstrated high accuracy, reaching 96.1% with an epoching time range of 500 ms following the stimulus event onset. The results revealed that the parietal-occipital brain region provides highly informative information for the classifier in the concealed visual searching tasks. Furthermore, the neural mechanism underlying the concealed visual-searching and decision-making process was explained by analyzing serial EEG components. The findings of this study could contribute to the development of a fault alert system, which has the potential to improve human decision-making performance.


First mutation in the voltage-gated Nav1.1 subunit gene SCN1A with co-occurring familial hemiplegic migraine and epilepsy.
Almost all mutations in the SCN1A gene, encoding the alpha(1) subunit of neuronal voltage-gated Na(V)1.1 sodium channels, are associated with severe childhood epilepsy. Recently, two mutations were identified in patients with pure familial hemiplegic migraine (FHM). Here, we identified a novel SCN1A L263V mutation in a Portuguese family with partly co-segregating hemiplegic migraine and epilepsy. The L263V mutation segregated in five FHM patients, three of whom also had epileptic attacks, occurring independently from their hemiplegic migraine attacks. L263V is the first SCN1A mutation associated with FHM and co-occurring epilepsy in multiple mutation carriers, and is the clearest molecular link between migraine and epilepsy thus far. The results extend the clinical spectrum associated with SCN1A mutations and further strengthen the molecular evidence that FHM and epilepsy share, at least in part, similar molecular pathways.