Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial.
Feeding during the first months of life might affect risk for celiac disease. Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow's milk proteins. Avoidance of cow's milk-based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies. We performed a randomized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease. We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes. The infants were randomly assigned to groups fed a casein hydrolysate formula (n = 113) or a conventional formula (control, n = 117) whenever breast milk was not available during the first 6-8 months of life. Serum samples were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase (anti-TG2A) using a radiobinding assay, to endomysium using an immunofluorescence assay, and antibodies to a deamidated gliadine peptide using an immunofluorometry assay. Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units. Cow's milk antibodies were measured during the first 2 years of life. Of the 189 participants analyzed for anti-TG2A, 25 (13.2%) tested positive. Of the 230 study participants observed, 10 (4.3%) were diagnosed with celiac disease. We did not find any significant differences at the cumulative incidence of anti-TG2A positivity (hazard ratio, 1.14; 95% confidence interval, 0.51-2.54) or celiac disease (hazard ratio, 4.13; 95% confidence interval, 0.81-21.02) between the casein hydrolysate and cow's milk groups. Children who developed celiac disease had increased titers of cow's milk antibodies before the appearance of anti-TG2A or celiac disease. In a randomized controlled trial of 230 infants with genetic risk factors for celiac disease, we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with cow's milk-based formula would decrease the risk for celiac disease later in life. Increased titers of cow's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life. ClinicalTrials.gov Number: NCT00570102.


Prostate cancer between prognosis and adequate/proper therapy.
Knowing the indolent, non-invasive nature of most types of prostate cancer, as well as the simple fact that the disease seems more likely to be associated with age rather than with other factors (50% of men at the age of 50 and 80% at the age of 80 have it [1], with or without presenting any symptom), the big challenge of this clinical entity was to determine severity indicators (so far insufficient) to guide the physician towards an adequate attitude in the clinical setting. The risk of over-diagnosing and over-treating many prostate cancer cases (indicated by all the major European and American studies) is real and poses many question marks. The present paper was meant to deliver new research data and to reset the clinical approach in prostate cancer cases.


The interplay between chromophore and protein determines the extended excited state dynamics in a single-domain phytochrome.
Phytochromes are a diverse family of bilin-binding photoreceptors that regulate a wide range of physiological processes. Their photochemical properties make them attractive for applications in optogenetics and superresolution microscopy. Phytochromes undergo reversible photoconversion triggered by the Z ⇄ E photoisomerization about the double bond in the bilin chromophore. However, it is not fully understood at the molecular level how the protein framework facilitates the complex photoisomerization dynamics. We have studied a single-domain bilin-binding photoreceptor All2699g1 (Nostoc sp. PCC 7120) that exhibits photoconversion between the red light-absorbing (Pr) and far red-absorbing (Pfr) states just like canonical phytochromes. We present the crystal structure and examine the photoisomerization mechanism of the Pr form as well as the formation of the primary photoproduct Lumi-R using time-resolved spectroscopy and hybrid quantum mechanics/molecular mechanics simulations. We show that the unusually long excited state lifetime (broad lifetime distribution centered at ∼300 picoseconds) is due to the interactions between the isomerizing pyrrole ring D and an adjacent conserved Tyr142. The decay kinetics shows a strongly distributed character which is imposed by the nonexponential protein dynamics. Our findings offer a mechanistic insight into how the quantum efficiency of the bilin photoisomerization is tuned by the protein environment, thereby providing a structural framework for engineering bilin-based optical agents for imaging and optogenetics applications.


A substrate selectivity and inhibitor design lesson from the PDE10-cAMP crystal structure: a computational study.
Phosphodiesterases (PDEs) catalyze the hydrolysis of second messengers cAMP and cGMP in regulating many important cellular signals and have been recognized as important drug targets. Experimentally, a range of specificity/selectivity toward cAMP and cGMP is well-known for the individual PDE families. The study reported here reveals that PDEs might also exhibit selectivity toward conformations of the endogenous substrates cAMP and cGMP. Molecular dynamics simulations and free energy study have been applied to study the binding of the cAMP torsional conformers about the glycosyl bond in PDE10A2. The computational results elucidated that PDE10A2 is energetically more favorable in complex with the syn cAMP conformer (as reported in the crystal structure) and the binding of anti cAMP to PDE10A2 would lead to either a nonreactive configuration or significant perturbation on the catalytic pocket of the enzyme. This experimentally inaccessible information provides important molecular insights for the development of effective PDE10 ligands.


Unilateral Isolated Congenital Ectopic Pupil (Corectopia) in a Four-Year-Old Child: Case Report and Literature Review.
Unilateral corectopia is an exceedingly rare congenital defect where the pupil is displaced from its central position. Usually, it presents with normal visual aperture or associated with other diseases. We describe the first reported case of a left ectopic pupil in a healthy four-year-old boy with normal lens structure and total lack of visual aperture. Reporting such instances contributes to the understanding of this condition and guide future research endeavors. Further studies are needed to reveal the underlying pathophysiology, refine treatment approaches, and assess long-term outcomes.


Examining the relationship between metformin dose and cancer survival: A SEER-Medicare analysis.
Cancer is a major health problem in the U.S and type 2 diabetes mellitus (T2DM) is known to increase the risk for the development of many cancers. Metformin, a first-line therapy for treating T2DM, is increasingly being used for its anticancer effects; however, the literature is limited on the effect of metformin dose on overall survival in patients with stage IV cancer. Overall survival was defined as the time interval from the date of diagnosis to the last known follow-up or death from any cause. Subjects who were alive on December 31, 2016 were censored. In this cohort study we examined the relationship between metformin dose and overall survival in persons with both T2DM and stage IV lung, breast, colorectal, prostate, or pancreas cancers. We used a retrospective study design with Cox proportional hazards regression analysis of the 2007-2016 of the Surveillance Epidemiology and End Results-Medicare (SEER) dataset. Of the 7,725 patients, 2,981(38.5%) had been prescribed metformin. Patients who used metformin had significantly better overall survival in both unadjusted (Unadjusted HR, 0.73; 95% CI, 0.69-0.76; p < 0.001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; p < 0.001). The overall survival between patients who took metformin with average daily dose ≥ 1000mg or < 1000mg were not statistically significant (aHR, 1.00; 95% CI, 0.93-1.08; p = 0.90). Metformin use regardless of dose is associated with increased overall survival in older adults with stage IV cancer.


Acute effects of foam rolling on passive tissue stiffness and fascial sliding: study protocol for a randomized controlled trial.
Self-myofascial release (SMR) aims to mimic the effects of manual therapy and tackle dysfunctions of the skeletal muscle and connective tissue. It has been shown to induce improvements in flexibility, but the underlying mechanisms are still poorly understood. In addition to neuronal mechanisms, improved flexibility may be driven by acute morphological adaptations, such as a reduction in passive tissue stiffness or improved movement between fascial layers. The aim of the intended study is to evaluate the acute effects of SMR on the passive tissue stiffness of the anterior thigh muscles and the sliding properties of the associated fasciae. In a crossover study design, 16 participants will receive all of the following interventions in a permutated random order: (1) one session of 2 × 60 s of SMR at the anterior thigh, (2) one session of 2 × 60 s of passive static stretching of the anterior thigh and (3) no intervention. Passive tissue stiffness, connective tissue sliding, angle of first stretch sensation, as well as maximal active and passive knee flexion angle, will be evaluated before and directly after each intervention. The results of the intended study will allow a better understanding of, and provide further evidence on, the local effects of SMR techniques and the underlying mechanisms for flexibility improvements. ClinicalTrials.gov, identifier: NCT02919527 . Registered on 27 September 2016.


External cephalic version with tocolysis. Observations and continuing experience at the Los Angeles County/University of Southern California Medical Center.
We considered 113 consecutive patients for attempted external cephalic version with tocolysis (ECV-T) after 37 weeks' gestation. We randomized the first patients to the control group (no ECV-T attempted, 23 patients) or the study group (ECV-T attempted, 25 patients). Nine patients were excluded, and ECV-T was then considered for 88 patients, with a success rate of 77% for the 104 total attempts. Six patients were lost to follow-up. In the successful ECV-T group, 71 of 75 patients (95%) presented the vertex in labor, while 4 patients (5%) reverted to breech. Uterine exploration at delivery revealed uterine anomalies in three of the patients who reverted. The cesarean rate was 25% in the successful-ECV-T group and 87% in the failed-ECV-T group. In the initial group, four patients (18%) spontaneously converted to cephalic presentations after 37 weeks. None of the failed-ECV-T patients spontaneously converted to cephalic presentations. The cesarean rate for the control and failed-ECV-T patients presenting the breech intrapartum was 88%. Complications included transient fetal bradycardia in 37 patients (36%), evidence of fetomaternal bleeding (positive Kleihauer-Betke test) in 2 patients (2%) and one fetal demise three weeks following successful ECV-T and diagnosed at the onset of labor. We lowered the cesarean section rate for breech presentation in labor with the selective application of ECV-T late in gestation. We consider this technique to be a powerful addition to our armamentarium for managing the term breech presentation.


Deconvolution of disoriented fiber diffraction data using iterative convolution and local regression.
Computationally efficient procedures are described for the deconvolution of disoriented fiber diffraction data to the resolution limit of measurable intensity in the patterns. The methods can be applied to diffraction data from imperfectly parallel arrays of one-dimensionally periodic rods or two-dimensionally periodic sheets, randomly rotated about their unique axes, to derive a representation of the intensity distribution corresponding to perfectly parallel orientation. With use of angular convolution and local angular regression, a set of uniform cylindrically averaged squared structure factors are iteratively adjusted, subject to a minimum-wavelength constraint, until they produce a disoriented pattern that fits the observed diffraction data. The results from this deconvolution provide a measure of the properly scaled cylindrically averaged squared structure factors, which can be used with other structural information to construct a physically plausible trial model suitable for further refinement. Sample deconvolutions of simulated X-ray patterns from partially oriented gap junction membranes are presented and the results from point-model deconvolutions are compared to those from constrained deconvolutions that began with the transform of a physically plausible trial model.


Cryosurgery for the immediate treatment of acute central airway obstruction.
Central airway obstruction commonly occurs in thoracic malignancies. Treatment is usually palliative but may be significantly challenging. Several endoscopic interventions are available to establish airway patency; however, their use is sometimes limited by certain factors like availability and high oxygen requirement. Cryosurgery has been established as a safe and effective technique for treatment of malignant airway obstruction, but its use has been limited to being adjunctive to other modalities and to low-grade stenosis. This is mainly due to the delayed effect and inability to achieve immediate airway patency. We report the successful use of this technique as stand-alone modality in a tracheal tumor with severe obstruction leading to acute respiratory failure. Immediate recanalization was achieved resulting in rapid resolution of symptoms.


[Protein microarray biosensor based on imaging ellipsometry and its biomedical applications].
A protein microarray biosensor based on imaging ellipsometry has been developed as a high-throughput and fast technique for protein analysis. As an automatic technique, it has advanced properties such as label-free, multi-protein simultaneous detection, static or kinetic analysis for protein interaction, and qualitative or quantitative analysis. It has been used for the biomedical applications including tumor markers detection, hepatitis B test, protein competitive adsorption and kinetic visualization for protein interactions. It have demonstrated promising potential for further applications in biomedicine.


Analysis of the disposition of a novel p38 MAPK inhibitor, AKP-001, and its metabolites in rats with a simple physiologically based pharmacokinetic model.
5-[(2-Chloro-6-fluorophenyl)acetylamino]-3-(4-fluorophenyl)-4-(4-pyrimidinyl)isoxazole (AKP-001) is a potent p38 mitogen-activated protein kinase inhibitor that is being developed to specifically target the intestines for the treatment of inflammatory bowel disease. According to the ante-drug concept, AKP-001 was designed to be metabolized to inactive forms via the first-pass metabolism to avoid undesirable systemic exposure. The purpose of this study is to investigate the pharmacokinetic characteristics of AKP-001 and its metabolites (M1 and M2) in rats, utilizing a simple physiologically based pharmacokinetic (PBPK) model. In vitro metabolic activity of AKP-001 in the S9 fraction of rat liver was examined, and plasma concentration-time profiles were developed following intravenous and/or oral administration of AKP-001 and its metabolites. AKP-001 was primarily metabolized to M1; however, M2 was not detected in liver S9 fractions. In accordance with this observation in vitro, M2 was detected in plasma after oral dosing of AKP-001 with a lag time of 1.5 hours, but not after intravenous dosing. To analyze pharmacokinetics in rats in vivo, a simple PBPK model was developed by simultaneous fitting of the plasma concentrations after treatment with AKP-001 and its metabolites. The observed plasma concentration-time profiles of AKP-001 and metabolites were described by the model adequately. Intestinal and systemic exposures of AKP-001 were simulated using the model to assess the relationship between pharmacokinetics and efficacy/safety. Model analysis suggested that oral bioavailability of intestine-targeting ante-drugs should be low to avoid systemic side effects. The pharmacokinetic properties of AKP-001 meet this criterion owing to extensive first-pass metabolism.


Explainable Classification of Benign-Malignant Pulmonary Nodules With Neural Networks and Information Bottleneck.
Computerized tomography (CT) is a clinically primary technique to differentiate benign-malignant pulmonary nodules for lung cancer diagnosis. Early classification of pulmonary nodules is essential to slow down the degenerative process and reduce mortality. The interactive paradigm assisted by neural networks is considered to be an effective means for early lung cancer screening in large populations. However, some inherent characteristics of pulmonary nodules in high-resolution CT images, e.g., diverse shapes and sparse distribution over the lung fields, have been inducing inaccurate results. On the other hand, most existing methods with neural networks are dissatisfactory from a lack of transparency. In order to overcome these obstacles, a united framework is proposed, including the classification and feature visualization stages, to learn distinctive features and provide visual results. Specifically, a bilateral scheme is employed to synchronously extract and aggregate global-local features in the classification stage, where the global branch is constructed to perceive deep-level features and the local branch is built to focus on the refined details. Furthermore, an encoder is built to generate some features, and a decoder is constructed to simulate decision behavior, followed by the information bottleneck viewpoint to optimize the objective. Extensive experiments are performed to evaluate our framework on two publicly available datasets, namely, 1) the Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) and 2) the Lung and Colon Histopathological Image Dataset (LC25000). For instance, our framework achieves 92.98% accuracy and presents additional visualizations on the LIDC. The experiment results show that our framework can obtain outstanding performance and is effective to facilitate explainability. It also demonstrates that this united framework is a serviceable tool and further has the scalability to be introduced into clinical research.


Asthma in women with endometriosis.
This study aimed to investigate asthma prevalence and severity in women with and without endometriosis. Before laparoscopy, asthma prevalence was evaluated in 879 women of reproductive age, undergoing surgery because of benign gynaecological conditions. Diagnosis of bronchial asthma was based on the American Thoracic Society criteria; asthma severity was classified in four categories according to the 2002 Global Initiative for Asthma guidelines. Asthmatic patients completed the Living with Asthma Questionnaire (LWAQ). Endometriosis was confirmed histologically and classified according to the revised American Fertility Society criteria. There were no significant differences in age, smoking status, and other demographic and health characteristics between patients with endometriosis (n = 467) and controls (n = 412). Asthma prevalence was similar in women with (23/467, 4.9%; 95% CI, 3.1-7.3) and without (22/412, 5.3%; 95% CI, 3.4-8.0; P = 0.781) endometriosis. Asthma severity was similar in women with and without endometriosis, with 12 (52.2%) women with endometriosis and 13 (59.1%) controls being in the intermittent (mildest) degree of severity. No significant difference was observed between women with and without endometriosis in the LWAQ total score. Women with endometriosis do not have an increased risk of having asthma.


The ABCDEF Bundle in Critical Care.
The ABCDEF bundle represents an evidence-based guide for clinicians to approach the organizational changes needed for optimizing intensive care unit patient recovery and outcomes. This article reviews the core evidence and features behind the ABCDEF bundle. The bundle has individual components that are clearly defined, flexible to implement, and help empower multidisciplinary clinicians and families in the shared care of the critically ill. The ABCDEF bundle helps guide well-rounded patient care and optimal resource utilization resulting in more interactive intensive care unit patients with better controlled pain, who can safely participate in higher-order physical and cognitive activities at the earliest point in their critical illness.


Clear cell papillary renal cell carcinoma: a case report and literature review.
Clear cell papillary renal cell carcinoma (CCPRCC), a type of low-grade renal cell neoplasm was recently included in the 2016 WHO classification of renal tumors (Tickoo SK, dePeralta-Venturina Mariza N, Harik LR, Worcester Heath D, Salama ME, Young AN et al. Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia. Am J Surg Pathol 30:141-153, 2006). While being recognized as its own entity, there is little research on CCPRCC. The specific tumor comprises of 9.3% of all renal tumors in young adults with an age range of 18-88 years (Wang Y, Ding Y, Wang J, Gu M, Wang Z, Qin C et al. Clinical features and survival of clear cell papillary renal cell carcinoma: 10-year retrospective study from two institutions. Oncology letters 16:1010-22, 2018.). In this article we provide recent understanding of CCPRCC and how to identify its distinct pathological entity. It is strongly positive for cytokeratin 7 (CK7), vimentin and mostly negative for CD10 and AMACR (Zhanyong B and John TE Clear cell papillary renal cell carcinoma in bilateral native kidneys after 2 year of renal transplantation: report of a case and review of literature. Case Reports in Transplantation 2011:11-4, 2011). Histopathologically, all cases of CCPRCC exhibited a tubular and papillary architecture, cuboidal tumor cells with clear cytoplasm and low Fuhrman grade (Wang Y, Ding Y, Wang J, Gu M, Wang Z, Qin C et al. Clinical features and survival of clear cell papillary renal cell carcinoma: 10-year retrospective study from two institutions. Oncology letters 16:1010-22, 2018; Kuroda N, Ohe C, Kawakami F, Mikami S, Furuya M, Matsuura K et al. Clear cell papillary renal cell carcinoma: a review. Int J Clin Exp Pathol 7: 7312-18, 2004.; Srigley JR, Delahunt B, Eble JN, Egevad L, Epstein JI, Grignon D, et al. The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. Am J surg Pathol. 37:1469-89, 2013). This case report and literature review highlights the cryptomorphic, immunohistochemical and cytogenic features of CCPRCC which will assist in understanding and managing these tumors.


[Acromegaly and Graves-Basedow disease. Report of 3 cases].
Acromegaly is associated to thyroidal disorders such as hyperthyroidism. The Graves-Basedow disease as a cause of thyroid hyperfunction is very infrequent, with only 8 cases having been reported up to 1993. The authors present 3 patients with acromegaly who developed hyperthyroidism due to Graves-Basedow disease in the course of their disease. Two of the patients had acromegaly of 30 years of evolution and the third patient underwent consultation for clinical symptoms of hyperthyroidism with acromegaly being simultaneously diagnosed. All the patients had weight loss prior to diagnosis and the possibility of neoplasia associated to acromegaly was excluded. The hyperthyroidism responded well to initial treatment with antithyroid drugs in the three cases. The authors conclude that hyperthyroidism should be taken into consideration in the diagnosis of a patient with acromegaly and weight loss.


Variations in the response of the thyroid gland of the rat to different low-iodine diets: correlation with iodine content of diet.
Large variations are frequently encountered in the thyroidal responses of rats to commercially available low-iodine diets. The major aim of this investigation was to attempt to correlate these variations with differences in the iodine content of the diets. A method was developed for measuring the iodine content of low-iodine diets which was sufficiently sensitive to discriminate between a diet containing 15-20 ng of iodine per g and one containing 30-40 ng of iodine per g. Large differences were observed between various commercial low-iodine diets in their ability to induce goiter and to affect other indices of thyroid function, and these differences could be correlated with differences in the iodine content. The most severe iodine deficiency occurred in rats that were fed a Remington diet containing 15-20 ng of iodine per g. After 3 months on this diet, thyroid weight increased about 7-fold, thyroid 127I concentration was reduced to about 0.5% of control values, serum thyroxine (T4) was reduced to less than 0.25 mug/100 ml, the ratio of labeled triiodothyronine to labeled T4 was increased to 5.2, and that of labeled monoiodotyrosine to labeled diiodotyrosine was increased to 4.2. Much smaller changes were observed in the rats on the other low-iodine diets, which ranged from 30-40 to about 100 ng of iodine per g. A daily supplement of only 0.2 mug of iodide per day administered to rats on a Remington low-iodine diet produced a significant changes in thyroidal responses. These results suggest that iodine deficiency alone is sufficient to explain the effects of the Remington low-iodine diet and that it is not necessary to postulate the presence of a goitrogen.


Local and systemic oxidative stress status in chronic obstructive pulmonary disease patients.
Previous studies have indicated that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). To study local and systemic oxidative stress status in COPD patients, and to clarify the relationship between local and systemic oxidative stress. Lipid peroxide malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and GSH peroxidase (GSH-PX) levels in induced sputum and plasma, as well as glucocorticoid receptor (GR) levels in peripheral blood leukocytes were examined in 43 acute exacerbation of COPD patients (group A), 35 patients with stable COPD (group B) and 28 healthy controls (14 smokers [group C]; 14 nonsmokers [group D]). MDA levels in induced sputum and plasma decreased progressively in groups A to D, with significant differences between any two groups (P<0.001). GSH, SOD and GSH-PX levels in both induced sputum and plasma increased progressively in groups A to D, with significant differences between any two groups (P<0.001). GR levels in peripheral blood leukocytes decreased progressively in groups D to A (all comparisons P<0.001). Pearson analysis revealed strong correlations between MDA, GSH, SOD and GSH-PX levels in plasma and induced sputum. The activity of SOD in plasma and sputum were both positively correlated with GR levels (partial correlation coefficients 0.522 and 0.574, respectively [P<0.001]). Oxidative stress levels were elevated in COPD patients. There was a correlation between local and systemic oxidative status in COPD, and between decreased SOD activity and decreased GR levels in COPD patients.


RAD001-mediated STAT3 upregulation and megakaryocytic differentiation.
RAD001 is currently used as an immunosuppressant and anticancer drug. Megakaryocyte (MK) differentiation includes development from pluripotent stem cells to proliferation and differentiation toward MK formation and platelet maturation. Our preliminary assay showed that RAD001 might stimulate MK differentiation; however, the exact regulatory mechanisms needed to be elucidated. By the ex vivo assay, RAD001 induced MK differentiation in human haematopoietic stem cells, with both the stimulation of CFU-GM colony formation and CD61 surface marker expression. Then, BALB/c mice were orally administrated with or without agrylin and/or RAD001 for 15 days. The platelet count and bone marrow CFU-MK colony formation were eliminated by agrylin, but unchanged in RAD001 and RAD001 plus agrylin mice. An ex vivo assay of bone marrow-derived stem cells demonstrated that RAD001 increased the number of CFU-MK colonies. The MK count in bone section indicated the decreased effect by agrylin and then recovered by RAD001. The level of plasma thrombopoietin was also enhanced in RAD001-treated mice. The effect of RAD001 on human leukaemic K562 and HEL cells showed the growth inhibition and MK differentiation activities; including morphological observation, CD41 and CD61 expression, and platelet factor 4 secretion. In RAD001-treated HEL cells, p-STAT3 expression, STAT3 translocation, and STAT3-DNA binding activity were up-regulated. Furthermore, STAT3 siRNA decreased the p-STAT3 and CD61 expression, as well as the CD61 fluorescence intensity, indicating that STAT3 may be critical in RAD001-mediated MK differentiation. Conclusion, the present study demonstrated that RAD001 might have the capacity to induce MK differentiation through the up-regulation of STAT3 signalling.


Sablefish (Anoplopoma fimbria) produce high frequency rasp sounds with frequency modulation.
Sablefish sounds, named rasps, were recorded at two captive facilities in British Columbia and Washington State. Rasps consisted of highly variable broadband trains of 2 to 336 ticks that lasted between 74 and 10 500 ms. The 260 rasps that were measured contained frequencies between 344 and 34 000 Hz with an average peak frequency of 3409 Hz. The frequency structure of ticks within rasps was highly variable and included both positive and negative trends. This finding makes sablefish one of the few deep-sea fish for which sounds have been validated and described. The documentation of sablefish sounds will enable the use of passive acoustic monitoring methods in fisheries and ecological studies of this commercially important deep-sea fish.


Interaction of a heralded single photon with nitrogen-vacancy centers in a diamond.
A simple, room-temperature, cavity- and vacuum-free interface for a photon-matter interaction is implemented. In the experiment, a heralded single photon generated by the process of spontaneous parametric down-conversion is absorbed by an ensemble of nitrogen-vacancy color centers. The broad absorption spectrum associated with the phonon sideband solves the mismatch problem of a narrow absorption bandwidth in a typical atomic medium and broadband spectrum of quantum light. The heralded single photon source is tunable in the spectral range 452 - 575 nm, which overlaps well with the absorption spectrum of nitrogen-vacancy centers.


Factors Affecting Permanent Sensorineural Hearing Loss and Bone Conduction in Patients After Receiving Radiotherapy to the Head and Neck Region.
This study aimed to investigate the factors affecting permanent sensorineural hearing loss (SNHL) and causing changes in bone conduction (BC) thresholds over time in patients after receiving radiotherapy (RT) or chemoradiotherapy (CRT) to the head and neck region. A total of 63 patients with irradiated HNC that were admitted to the Radiation Oncology Department between 2011 and 2018 were included in the study. All patients were assessed with pure tone audiometry at eight different time points (first before RT and last five years after completion of RT). A chi-square test was used to analyze the variables that affected permanent SNHL occurrence. Repeated measure analysis of variance was conducted to investigate the factors affecting change in the BC threshold at pure-tone average (0.5-2 kHz) and the air conduction (AC) threshold at 4 and 6 kHz frequencies over time. Median follow-up was 52 months (range, 12-110 months). SNHL was found in 18 (14%) of the 126 ears. According to the receiver operating characteristic analysis, the cut-off values of cochlear Dmean and Dmax radiation doses were 40 Gy [p=0.017, area under the curve (AUC): 0.676] and 45 Gy (p=0.008, AUC: 0.695). Dmean (≤40 Gy vs. >40 Gy) and Dmax (≤45 Gy vs. >45 Gy) cochlear doses and age (≤40 vs. >40 years) were determined as factors affecting SNHL in the chi-square test. Repeated measures showed that BC thresholds between 0.5-2 kHz and AC thresholds at 4 and 6 kHz increased over time. Age (≤40 vs. >40 years), treatment of head and neck cancer (RT vs. CRT), cisplatin use, and Dmean (≤40 Gy vs. >40 Gy) and Dmax cochlear dose (≤45 Gy vs. >45 Gy) were important factors affecting the course of BC threshold over time. Dmean and Dmax cochlear doses and age were found to be associated with permanent SNHL. Conduction thresholds worsened over time at all frequencies, and this trend was affected by cochlear doses, age, CRT, and cisplatin use.


Inhibition of RecBCD in Klebsiella pneumoniae by Gam and its effect on the efficiency of gene replacement.
Gam protein is an inhibitor of the host RecBCD exonuclease, and this inhibition is essential to the proficiency of Red recombinase-mediated gene replacement. In Klebsiella pneumoniae, the efficiency of this gene replacement was lower than that in Escherichia coli, and the minimum length of homologous extensions required was longer. Thus, it was supposed that the inhibitory effect of Gam against RecBCD was weak in K. pneumoniae. To test this hypothesis, a Gam-deficient Red recombinase expression plasmid and a ΔrecB K. pneumoniae mutant were constructed. The Gam-deficient Red recombinase showed a reduced capacity for gene replacement compared with that of the complete Red recombinase. The efficiency of gene replacement in the ΔrecB mutant was 6-8 times higher than the wild-type strain, and the minimum length for the homologous extensions was reduced to 100 bp. These results indicate that Gam does inhibit the RecBCD exonuclease in K. pneumoniae, but that this inhibition is not stringent. Furthermore, mutation of recB presents a convenient and efficient method to enhance the Red recombinase assisted gene replacement in K. pneumoniae.


[Progress of the Mechanism of Acupuncture to Promote Repair of Facial Nerve Injury].
Facial nerve injury results in facial muscle movement disorders that interferes with patient's life. Acupuncture is an effective therapy for facial nerve injury, but its mechanism has not been clarified. The evidence supports that acupuncture can accelerate the repair of facial nerve injury by adjusting the electric wave of patient's facial muscle, improving facial blood circulation, and promoting the expression of cell and protein molecule.


Odor, Not Performance, Dictates Bemisia tabaci's Selection between Healthy and Virus Infected Plants.
Although, insect herbivores are generally thought to select hosts that favor the fitness of their progeny, this "mother-knows-best" hypothesis may be challenged by the presence of a plant virus. Our previous study showed that the whitefly, Bemisia tabaci, the obligate vector for transmitting Tomato yellow leaf curl virus (TYLCV), preferred to settle and oviposit on TYLCV-infected rather than healthy host plant, Datura stramonium. The performances of B. tabaci larvae and adults were indeed improved on virus-infected D. stramonium, which is consistent with "mother-knows-best" hypothesis. In this study, B. tabaci Q displayed the same preference to settle and oviposit on Tomato spotted wilt virus (TSWV)-infected host plants, D. stramonium and Capsicum annuum, respectively. As a non-vector of TSWV, however, insect performance was impaired since adult body size, longevity, survival, and fecundity were reduced in TSWV infected D. stramonium. This appears to be an odor-mediated behavior, as plant volatile profiles are modified by viral infection. Infected plants have reduced quantities of o-xylene and α-pinene, and increased levels of phenol and 2-ethyl-1-hexanol in their headspace. Subsequent behavior experiments showed that o-xylene and α-pinene are repellant, while phenol and 2-ethyl-1-hexanol are attractive. This indicates that the preference of B. tabaci for virus-infected plants is modulated by the dynamic changes in the volatile profiles rather than the subsequent performances on virus-infected plants.


Mapping of chromosome 17 breakpoints in acute myeloid leukemias.
The 17q11-21 chromosomal region is frequently involved in non-random structural rearrangements associated with the M1 and M2 subtypes of acute myeloid leukemias (AML), as well as with the 15;17 translocation typical of the promyelocytic subtype. A number of genes have been localized in this region including the c-erbA-1 and c-erbB-2 proto-oncogenes, the genes coding for the granulocyte-colony stimulating factor (G-CSF), the retinoic acid receptor alpha (RAR alpha) and the myeloperoxidase enzyme (MPO). However, the precise location of these genes in relationship to the 17q11-21 breakpoint(s) has not been determined. Using in situ hybridization on metaphase chromosomes, we established the position of the breakpoints in relationship to the c-erbA-1, c-erbB-2, G-CSF, RAR alpha and MPO loci in a series of AML cases bearing 17q11-21 rearrangements. We report: (i) that the respective position of the five genes is centromere - c-erbA-1 - G-CSF - c-erbB-2 - RAR alpha - MPO - telomere; (ii) that the breakpoints of the various AML subtypes are variably located between the centromere and c-erbB-2 in M1 and M2; (iii) that the breakpoints are consistently located between c-erbB-2 and RAR alpha/MPO in M3; and (iv) that the breakpoint on chromosome 17 in the 15;17 translocation is located on 17q21 and not on 17q11-12 as previously reported.


Characterization of verotoxigenic Escherichia coli (VTEC) isolates from faeces of small ruminants and environmental samples in southern Jordan.
This study was conducted to determine the prevalence rate of VTEC in slaughtered sheep and goats and to evaluate the contamination rate of VTEC in slaughterhouses and butchers' shops in southern Jordan. 201 E. coli isolates from animals' faecal samples and 33 E. coli isolates from slaughterhouse/butcher shop samples were characterized by multiplex PCR (mPCR) reaction for detection of stx1, stx2, eae A and E-hly A virulent genes. Twenty-six virulent E. coli isolates were characterized by mPCR to seven different virulent patterns: stx1, stx1+stx2, stx1+eae A, stx1+E-hly A, stx1+eae A+E-hly A, eae A and E-hly A. It was found that VTEC comprised 6.4% and 21% of the total E. coli isolates from slaughtered small ruminants and slaughterhouses/ butchers' shops, respectively. The VTEC comprised 76.2% of the virulent isolates. The proportion of stx1:stx1+stx2 patterns was 19:1. It was found that the characterized complex VTEC (containing eae A and/or E-hly A) possessed three virulence patterns, including (VTEC) stx1 +eae A, (VTEC/EHEC) stx1 +E-hly A and (VTEC/EHEC) stx1 +eae A +E-hly A in percentages of 30%, 25% and 10%, respectively, in relation to the total VTEC isolates. Only two VTEC isolates were characterized as E. coli O157 and O26 serotypes, as highly pathogenic strains. Each of the O157 and O26 VTEC isolates was in a percentage of 0.4% in relation to the total E. coli isolates with virulent patterns stx1, eae A and E-hly A. The rest of the VTEC isolates were non-O157 VTEC. The antibiotic sensitivity test showed that the isolated VTEC was highly sensitive to gentamicin and co-trimoxazole and highly resistant to tetracycline and ampicillin.


[Synthetic salmon calcitonin. Treatment of choice in Sudeck's disease].
56 cases of primary and post-traumatic Sudeck's disease, treated with Sandoz synthetic salmon calcitonine are reported. The results obtained suggest that this drug should be considered of choice in this type of pathology provided it is administered with the right, highish doses. 2 completely cured cases of stemming of bone cyst using the same product are also reported.


Biocompatibility comparison of novel soft tissue implants vs commonly used biomaterials in a pig model.
To develop a model to evaluate biocompatibility, integration, and substrate independence of novel porous bioscaffolds for maxillofacial and plastic reconstruction using sphere-templated angiogenic regeneration technology compared with currently available synthetic and biologic soft tissue implants. A prospective pilot study using animals. Military medical center. Five pigs underwent dorsal subcutaneous implantation of a polypropylene-based material coated with precision pore silicone granules (sphere-templated scaffold), expanded polytetrafluoroethylene, human dermis, and porcine dermis. Sham and undissected sites were also used as controls. Specimens were harvested 7, 21, 90, and 180 days after surgery and evaluated histologically for inflammation, neovascularization, and collagen deposition. All materials and sham sites induced a mild to moderate inflammation that decreased over time, except for human dermis, which elicited a moderate to severe inflammatory response. The responses were varied and measurable using subjective scoring methods. The sphere-templated scaffold demonstrated numerous foreign body giant cells adjacent to the silicone granules, which were not seen in any of the other specimens. Subjective scoring of pathology slides and measurement of capsule thickness appeared to show differences between the materials, but these differences require a larger number of subjects and proper statistical analysis to assess. The robust foreign body reaction elicited by the polypropylene/silicone-based scaffold argues against the use of this material in future studies. The authors advocate using inert biodegradable substances for future bioscaffold constructs.


Which pen? A comparative study of surgical site markers.
A preoperative requirement is the correct and clear marking of a specific surgical site. We aimed to compare the ability of marker pens to withstand surgical preparation. Five volunteers with different Fitzpatrick skin types were marked with ten pens. Marked skin sites were prepared with chlorhexidine followed by chlorhexidine, betadine followed by chlorhexidine, and betadine followed by betadine. Each site was photographed in theatre. Two volunteers ranked the top three most visible marker pens from each photograph. The results showed that Sharpie® W10 black, Dual Tip (Purple Surgical), and Easimark modern regular tip (Leonhard Lang) were the best performers across all skin types. Red pen should be avoided with betadine skin preparation. The study concludes that the above named three markers are the best at withstanding surgical skin preparation. Different skin types require different colour ink for maximal clarity in marking. Biro and drywipe markers should never be used for surgical marking.


Sequential duplications of an ancient member of the DnaJ-family expanded the functional chaperone network in the eukaryotic cytosol.
Across eukaryotes, Hsp70-based chaperone machineries display an underlying unity in their sequence, structure, and biochemical mechanism of action, while working in a myriad of cellular processes. In good part, this extraordinary functional versatility is derived from the ability of a single Hsp70 to interact with an array of J-protein cochaperones to form a functional chaperone network. Among J-proteins, the DnaJ-type is the most prevalent, being present in all three kingdoms and in several different compartments of eukaryotic cells. However, because these ancient DnaJ-type proteins diverged at the base of the eukaryotic phylogeny, little is understood about the evolutionary basis of their diversification and thus the functional expansion of the chaperone network. Here, we report results of evolutionary and experimental analyses of two more recent members of the cytosolic DnaJ family of Saccharomyces cerevisiae, Xdj1 and Apj1, which emerged by sequential duplications of the ancient YDJ1 in Ascomycota. Sequence comparison and molecular modeling revealed that both Xdj1 and Apj1 maintained a domain organization similar to that of multifunctional Ydj1. However, despite these similarities, both Xdj1 and Apj1 evolved highly specialized functions. Xdj1 plays a unique role in the translocation of proteins from the cytosol into mitochondria. Apj1's specialized role is related to degradation of sumolyated proteins. Together these data provide the first clear example of cochaperone duplicates that evolved specialized functions, allowing expansion of the chaperone functional network, while maintaining the overall structural organization of their parental gene.


Y chromosomes: born to be destroyed.
Suppression of recombination is the prerequisite for stable genetically determined sex systems. A consequence of suppression of recombination is the strong bias in the distribution of transposable elements (TEs), mostly retrotransposons. Our results and those from others indicate that the major force driving the degeneration of Y chromosomes are retrotransposons in remodelling former euchromatic chromosome structures into heterochromatic ones. We put forward the following hypotheses. (1) A massive accumulation of retrotransposons occurs early in non-recombining regions. (2) Heterochromatic nucleation centres are formed as a genomic defence mechanism against invasive parasitic elements. The newly established nucleation centres become epigenetically inherited. (3) Spreading of heterochromatin from the nucleation centres into flanking regions induces, in an adaptive process, transcriptional gene silencing of neighbourhood genes that could either be still intact or in an already eroded condition. (4) Constitutive silenced genes are not under the same genetic selection pressure as active genes. They are more exposed to the decay process. (5) Gene dosage balance is re-established by the parallel evolution of dosage compensation mechanisms.


Realistic kinetic loading of the jaw system during single chewing cycles: a finite element study.
Although knowledge of short-range kinetic interactions between antagonistic teeth during mastication is of essential importance for ensuring interference-free fixed dental reconstructions, little information is available. In this study, the forces on and displacements of the teeth during kinetic molar biting simulating the power stroke of a chewing cycle were investigated by use of a finite-element model that included all the essential components of the human masticatory system, including an elastic food bolus. We hypothesised that the model can approximate the loading characteristics of the dentition found in previous experimental studies. The simulation was a transient analysis, that is, it considered the dynamic behaviour of the jaw. In particular, the reaction forces on the teeth and joints arose from contact, rather than nodal forces or constraints. To compute displacements of the teeth, the periodontal ligament (PDL) was modelled by use of an Ogden material model calibrated on the basis of results obtained in previous experiments. During the initial holding phase of the power stroke, bite forces were aligned with the roots of the molars until substantial deformation of the bolus occurred. The forces tilted the molars in the bucco-lingual and mesio-distal directions, but as the intrusive force increased the teeth returned to their initial configuration. The Ogden material model used for the PDL enabled accurate prediction of the displacements observed in experimental tests. In conclusion, the comprehensive kinetic finite element model reproduced the kinematic and loading characteristics of previous experimental investigations.


Cholesteryl ester acyl oxidation and remodeling in murine macrophages: formation of oxidized phosphatidylcholine.
Cholesterol is an essential component of eukaryotic cell membranes, regulating fluidity and permeability of the bilayer. Outside the membrane, cholesterol is esterified to fatty acids forming cholesterol esters (CEs). Metabolism of CEs is characterized by recurrent hydrolysis and esterification as part of the CE cycle; however, since recombinant 15-lipoxygenase (15-LO) was shown to oxidize cholesteryl linoleate of LDL, there has been interest in CE oxidation, particularly in the context atherogenesis. Studies of oxidized CE (oxCE) metabolism have focused on hydrolysis and subsequent reverse cholesterol transport with little emphasis on the fate the newly released oxidized fatty acyl component. Here, using mass spectrometry to analyze lipid oxidation products, CE metabolism in murine peritoneal macrophages was investigated. Ex vivo macrophage incubations revealed that cellular 15-LO directly oxidized multiple CE substrates from intracellular stores and from extracellular sources. Freshly harvested murine macrophages also contained 15-LO-specific oxCEs, suggesting the enzyme may act as a CE-oxidase in vivo. The metabolic fate of oxCEs, particularly the hydrolysis and remodeling of oxidized fatty acyl chains, was also examined in the macrophage. Metabolism of deuterated CE resulted in the genesis of deuterated, oxidized phosphatidylcholine (oxPC). Further experiments revealed these oxPC species were formed chiefly from the hydrolysis of oxidized CE and subsequent reacylation of the oxidized acyl components into PC.


A family of non-allelic tRNA(ValGUU) genes from the cellular slime mold Dictyostelium discoideum.
A haploid genome of the cellular slime mold Dictyostelium discoideum contains at least 14 non-allelic gene copies coding for a tRNA(ValGUU). The structure, genomic organization, and expression of these genes have been analyzed in relation to stages of the developmental cycle. So far, 13 tRNA(ValGUU) genes have been isolated and characterized. All genes contain identical mature tRNA-coding regions, and consequently identical gene internal promoter elements. However, different genes differ with respect to their 5'- and 3'-flanking regions, although a certain degree of sequence conservation seems apparent. Different members of this tRNA gene family appear to be randomly dispersed along the seven D. discoideum chromosomes, and not clustered at any one genomic location. In vivo expression of individual genes was studied in yeast. All but one tRNA(ValGUU) gene are actively transcribed, though with different efficiencies. There is also evidence that not all of these tRNA genes are constitutively transcribed in Dictyostelium throughout the developmental cycle. One characteristic primary transcript can only be detected in cells of the late preaggregation phase, whereas growing cells, cells in the stationary phase or cells harvested 4 h after the onset of development do not seem to carry this transcript. This product seems to be transcribed from a gene of an unusual structure. Although this particular gene has not yet been isolated, it can be predicted from the sequence of the cDNA synthesized from primary transcription products of this putative gene, that it is composed of nt 1-54 of a 3'-truncated tRNA(ValGUU) gene linked to a bona fide tRNA(ValGUU) gene.


Sample size determination for the confidence interval of linear contrast in analysis of covariance.
This article provides a way to determine sample size for the confidence interval of the linear contrast of treatment means in analysis of covariance (ANCOVA) without prior knowledge of the actual covariate means and covariate sum of squares, which are modeled as a t statistic. Using the t statistic, one can calculate the appropriate sample size to achieve the desired probability of obtaining a specified width in the confidence interval of the covariate-adjusted linear contrast.


Pathogenetic analysis of certain developmental and genetic ectodermal defects.
It is postulated that, in the nevoid basal cell carcinoma syndrome, independent mosaic pleiotropic action of the mutant gene on morphogenesis and histogenesis produces primary malformations of midline and nonmidline structures and dysplasias more or less highly predisposed to cancer development. However, in focal dermal hypoplasia and the Bartsocas-Papas syndrome, it is highly tempting to postulate that embryonic dysplasias, ie, breakdown or necrosis of ectoderm, especially in the region of the Ekdodermring, are responsible for the production of many of the congenital anomalies seen in these patients, and that these anomalies more likely represent sequences rather than primary malformations. The sequences in the type 1 fetal epidermal dysplasias probably represent mucosal breakdown, producing various upper gut atresias and an epidermal "disease" with loss of epidermis and many severe secondary consequences. Polyhydramnios, micrognathia, "arthrogryposis," reduced fetal growth, and short umbilical cord are other consequences of fetal hypokinesia due to stiff skin in the type 2 fetal epidermal dysplasias, with severe muscle involvement in the Hutterite-Mennonite type possibly responsible for additional fetal hypokinesia. Thus it seems likely that embryonic and fetal dysplasias can now be held responsible, directly and indirectly, for a fascinating variety of human congenital anomalies.


A systematic review of the evidence for hypodermoclysis to treat dehydration in older people.
The purpose of the study was to evaluate the evidence supporting the use of hypodermoclysis (i.e., subcutaneous infusion of fluids) to treat dehydrated elderly patients, and to discuss clinical applications of this mode of therapy in the long-term care setting. Articles reporting the use of hypodermoclysis were identified using a systematic MEDLINE search between January 1966 and May 1996. Articles were included in our sample if they contained original patient data that evaluated either the efficacy or adverse effects associated with the use of subcutaneous infusions to treat dehydration in adults, whether hyaluronidase was required to facilitate the absorption of subcutaneous fluid, or if potassium could be added to the solution. Eighteen articles met the inclusion criteria. Since we hypothesized that adverse effects associated with hypodermoclysis may have been related largely to the use of nonelectrolyte or hypertonic solutions, the studies were evaluated according to the type of fluid administered. Six hundred and eighty-five patients were described in 13 studies evaluating the efficacy and toxicity of subcutaneously administered fluid. Four studies evaluated hypodermoclysis using electrolyte-containing solutions in 25 patients. Two of these were randomized control trials (RCT) that compared hypodermoclysis to intravenous therapy. Both reported similar absorption of fluids. In the single RCT that evaluated adverse effects, 4 of 17 patients receiving hypodermoclysis reported minor side effects similar to those reported with intravenous therapy. Adverse effects were more severe when electrolyte-free or hypertonic solutions were evaluated. Of the 639 patients who may have received electrolyte-free solutions, 16 patients (2.5%) reported adverse effects, 8 of which were severe. Both patients reported to have received hypertonic solutions noted adverse effects, one of which was severe. The use of hyaluronidase to facilitate absorption was evaluated in 74 patients. These studies suggest that hyaluronidase improves the speed of fluid absorption but may not change the patient's comfort level. A single case report of 350 subcutaneous infusions in 67 patients investigated the administration of up to 34 mmol/L of potassium chloride (KCl) by hypodermoclysis. The only adverse reaction observed was discomfort at the infusion site. Hypodermoclysis can be used to most safely provide fluids when electrolyte-containing fluids are administered. Hypodermoclysis may have fallen into disuse because of reports of severe adverse reactions related to infusions of electrolyte-free or hypertonic solutions that would likely be considered inappropriate today. Whether or not hyaluronidase is required to promote subcutaneous fluid absorption remains unresolved. Limited evidence suggests that potassium chloride may, with caution, be safely added to subcutaneous infusions. The majority of the available studies evaluating hypodermoclysis are of poor quality. Because of the tremendous potential benefits of administering fluid subcutaneously, there is a need for good quality studies to evaluate the efficacy of hypodermoclysis.


Intravascular missile: apparent retrograde course from the left ventricle.
An air gun pellet was found in the right superior pulmonary vein after penetrating the left ventricle of a 14 year old boy. This apparent retrograde movement in the left side of the heart has not been reported previously.


[Comparative pharmacokinetics of syringin, eleutheroside E and isofraxidin in rat plasma after intravenous administration of each monomer and Ciwujia injection].
To compare the pharmacokinetics of syringin, eleutheroside E and isofraxidin after intravenous administration of each monomer and Ciwujia injection. Twenty-four Sprague-Dawley rats were randomly divided into four groups and intravenously administrated with syringin, eleutheroside E, isofraxidin, and Ciwujia injection, respectively. The concentrations of the three components in rat plasma were determined by LC-MS/MS. DAS 2.0 software was applied to calculate the pharmacokinetic parameters while the SPSS 17.0 software was used for statistical analysis. Significant difference (P < 0.05) was found between each monomer and the injection on the main pharmacokinetic parameters such as AUC, CL and t1,/2. Compared with the injection, the group treated with the syringin has obvious decrease in AUC, and increase in CL while the group treated with eleutheroside E has obvious increase in AUC, and decrease in CL The t1/2 of isofraxidin was prolonged in Ciwujia injection. Pharmacokinetic characters of the ingredients in the injection varied greatly from the monomer. Other constituents in the injection may have an impact on the pharmacokinetic profiles of these three components.


Obstructive Sleep Apnea and Hypertension: A Review of the Relationship and Pathogenic Association.
Obstructive sleep apnea (OSA) is defined as episodes of hypopnea or apnea, which leads to a partial or complete block of airways. Hypertension, on the other hand, is defined as an increase in systemic arterial blood pressure to a certain threshold. OSA and hypertension share many common factors in pathophysiology, such as gender, obesity, unhealthy lifestyle, impaired quality of sleep, renin-angiotensin system, and increased fluid distribution. In order to manage our patients effectively, we need to explore further the correlation between the two conditions.


Steroid hormone receptors and oncogenes.
Steroid hormones exert diverse effects on normal growth and development through the action of specific intracellular receptor molecules. These receptors are thought to function as trans-acting regulatory proteins by interacting with chromatin and modulating the transcription of specific genes in target cells. Another class of molecules, the viral oncogenes (v-oncs) encode proteins which are associated with the transformation of normal cells to cancer cells. The cellular oncogenes (proto-oncogenes), from which the viral oncogenes were derived, may have important roles in the growth and differentiation of normal cells. Steroid hormones, directly or in conjunction with altered oncogene products, also appear to be important in the growth and differentiation of cancer cells. Recently it has been determined that the amino acid sequences of the steroid receptors are similar to the erb-A oncogene product, which subsequently has been found to be a thyroid hormone receptor. These results have led to the hypothesis that the steroid receptors and the erb-A product are members of a superfamily of transcription factors which regulate normal and malignant growth and differentiation. Similarities and functional interactions between steroid receptors and oncogene products will be the focus of this review. The results to date imply that these two classes of molecules have interesting and important inter-relationships.


Improved hypertension management and control: results from the health survey for England 1998.
A survey in 1994 showed that among the 20% of the adult English population who were identified as hypertensive, approximately 30% had their blood pressures controlled to <160 mm Hg systolic and <95 mm Hg diastolic. The 1998 Health Survey for England data update the 1994 findings in light of new thresholds and targets for treatment outlined in recent national and international guidelines. This cross-sectional survey is analyzed to describe the prevalence, awareness, treatment, and control of hypertension in a random, nationally representative sample of 11 529 English adults (>/=16 years) living in noninstitutional households in 1998 and to compare these rates with those from 1994. In 1998, 20% and 37% of adults were hypertensive according to the old (systolic >/=160 mm Hg or diastolic >/=95 mm Hg) and new (systolic >/=140 mm Hg or diastolic >/=90 mm Hg) definitions, respectively. Corresponding values in 1994 were 20% and 38%. Treatment and control rates among hypertensive adults (new definition) improved from 26% to 32% and from 6% to 9%, respectively, although 60% of those on treatment received only 1 antihypertensive drug in both years. Among persons with controlled hypertension, 59% reported having received nonpharmacological advice from their physicians in 1998 compared with 30% in 1994. Rates of hypertension treatment and control have increased significantly (P=0.05 and P<0.01, respectively) since 1994 but remain low by international standards. The 1998 data suggest that improved detection, greater use of nonpharmacological measures, and increased use of >1 antihypertensive agent per patient would produce greater success in achieving target levels. This could lead to major reductions in fatal and nonfatal cardiovascular events.


Fish tank granuloma.
A case of fish tank granuloma is presented. A lesional biopsy sample yielded growth of Mycobacterium marinum on Löwenstein's medium. Treatment with cotrimoxazole was successful.


ALPHA: a toolkit for Automated Local PHylogenomic Analyses.
The evolutionary histories of individual regions across a genomic alignment-called 'local genealogies'-can differ from each other, due to processes such as recombination. Elucidating and analyzing these local genealogies are important for a large number of inference tasks, including those pertaining to species phylogenies, evolutionary processes and trait mapping. In this paper, we present a toolkit for automated local phylogenomic analyses, or ALPHA. The purpose of this toolkit is to provide a wide array of functionalities for automated inference of local genealogies as well as analyses based on these local genealogies. The toolkit uses sliding windows to construct local genealogies and can compute a wide array of local phylogeny based statistics, such as the D-statistic. The toolkit comes with a graphical user interface and several import/export functionalities. Over the last few decades, much emphasis in phylogenomics has been put on developing tools for inferring species phylogenies. This toolkit complements those efforts by emphasizing the 'local' aspect of phylogenomics. ALPHA is freely available for installation and use, including source code, at https://github.com/chilleo/ALPHA.


Ordering of lipid A-monophosphate clusters in aqueous solutions.
In this investigation, a study of the self-assembly of electrostatically stabilized aqueous dispersions of nanometric lipid A-monophosphate clusters from Escherichia coli was carried out in three different volume-fraction regimes. The experimental techniques used in the investigation were osmotic pressure, static and quasielastic light scattering, scanning electron microscopy and transmission electron microscopy, and small-angle x-ray scattering. Experiments were carried out at low ionic strength (I=0.1-5.0 mM NaCl) at 25 degrees C. At volume fractions between 1.5x10(-4)<or=phi<or=5.4x10(-4), the lipid A-monophosphate clusters had an average rms hydrodynamic diameter of d=7.5 nm, and a weighted-average molecular weight of (1.78+/-0.23)x10(5) g mol(-1). Quasielastic light scattering (LS) experiments yield similar values for the particle size and particle size distribution compared to electron microscopy, small-angle x-ray scattering, and LS experiments. When the volume fraction was increased to a higher regime 5.4x10(-4)<or=phi<or=9.50x10(-4), much larger clusters of lipid A monophosphate formed. The clusters detected in this volume-fraction range were assembled from between 8 and 52 of the d=7.5 nm clusters and the assemblies are densely packed in such a way that colloidal crystals composed of the monodisperse microspheres are in physical contact with their nearest neighbors. Clusters that formed in volume fractions between 10.0x10(-4)<or=phi<or=40.0x10(-4) revealed a weighted-average molecular weight of (10.15+/-0.17)x10(6) g mol(-1) and a hydrodynamic diameter of approximately d=70.6 nm. The crossover volume fraction between the small and the large clusters appeared at phicr=5.05x10(-4). In the intermediate volume-fraction range, the scattered intensity I(Q) vs Q curves (light and x rays) showed asymptotic behavior. From the asymptotic curves, the scattered intensity, the relationship between the average mass and radius, and the fractal dimension df were determined. The df value, which was evaluated from the expression I(Q) proportional, RGdf, was found to be 1.67+/-0.03, a value that was virtually independent of the ionic strength (0.1-5.0 mM NaCl) at 25 degrees C. Even at a very low ionic strength (I=0.10 mM NaCl), lipid A monophosphate formed a number of differently shaped clusters. Electron microscope images showed that two types of self-assembled clusters existed at the lowest volume-fraction range studied and also dominated the images taken at the higher volume-fraction regimes. One type of cluster showed a cubic morphology and a size variation of 50-100 nm, while another type took on the appearance of a quadratic cylinder, with dimensions of 50x150 nm2. The other clusters appeared in various shapes: dimers, trimers, and distorted tetramers, which were quite different from the ones previously observed for lipid A diphosphate. Small-angle x-ray diffraction experiments on lipid A-monophosphate clusters suspended in water, containing 5 mM NaCl (25 degrees C), indicated the existence of long-range order of d=7.5 nm. At low polydispersity, two distinct types of lipid A-monophosphate colloidal clusters were able to form at low polydispersity and were subsequently identified using light scattering, small-angle x-ray scattering, and selected-area electron diffraction. From an analysis of experimental results obtained from these clusters, distinct peaks could be assigned to a body-centered cubic (bcc) lattice, with a=49.5+/-1.8 nm. The solution structure found for lipid A diphosphate at volume fractions of 3.75x10(-4)<or=phi<or=4.15x10(-4) also exhibited a (bcc)-type lattice; however, a=36.1 nm [C. A. Faunceet al. J. Phys. Chem. 107, 2214 (2003)]. Using the particle and cluster properties determined from small-angle x-ray scattering, light scattering, and osmotic-pressure measurements as a function of volume fraction, good agreement was found between the directly measured osmotic-pressure values and those calculated from scattering experiments.


FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity.
Hypoxia-inducible factor 1 (HIF-1) is a master regulator of oxygen homeostasis that controls angiogenesis, erythropoiesis, and glycolysis via transcriptional activation of target genes under hypoxic conditions. O(2)-dependent binding of the von Hippel-Lindau (VHL) tumor suppressor protein targets the HIF-1alpha subunit for ubiquitination and proteasomal degradation. The activity of the HIF-1alpha transactivation domains is also O(2) regulated by a previously undefined mechanism. Here, we report the identification of factor inhibiting HIF-1 (FIH-1), a protein that binds to HIF-1alpha and inhibits its transactivation function. In addition, we demonstrate that FIH-1 binds to VHL and that VHL also functions as a transcriptional corepressor that inhibits HIF-1alpha transactivation function by recruiting histone deacetylases. Involvement of VHL in association with FIH-1 provides a unifying mechanism for the modulation of HIF-1alpha protein stabilization and transcriptional activation in response to changes in cellular O(2) concentration.


Lateral femoral scan: an alternative method for assessing bone mineral density in children with cerebral palsy.
Children with cerebral palsy (CP), often nonambulatory and/or on anticonvulsants, are at increased risk for fractures. Bone mineral density (BMD) measured by the conventional techniques of dual-energy X-ray absorptiometry (DXA) often cannot be reliably or easily measured in these patients. To find an alternative site to whole body, spine and hip that can be conveniently used to measure BMD in CP patients. Having observed that CP patients prefer to lie on their sides, we explored measuring BMD at the distal femur in the lateral projection. A total of 92 scans were performed without sedation in 34 children and adolescents with CP, aged 4-19 years. Four femoral shaft subregions were created: two trabecular and two cortical. The coefficients of variation (CV %) were generally higher for opposite-side comparisons (n = 12 patients) than for same-side comparisons (n = 16 patients). For intra- and interobserver analyses, CV % were higher for cortical regions than for trabecular regions. Overall, the CV % were similar to those for hip and spine. This peripheral site in the femur should be considered as an alternative for patients with CP when whole-body, hip and spine DXA are not practical.


Characterization of subclinical ZIKV infection in immune-competent guinea pigs and mice.
An infectious agent's pathogenic and transmission potential is heavily influenced by early events during the asymptomatic or subclinical phase of disease. During this phase, the presence of infectious agent may be relatively low. An important example of this is Zika virus (ZIKV), which can cross the placenta and infect the foetus, even in mothers with subclinical infections. These subclinical infections represent roughly 80 % of all human infections. Initial ZIKV pathogenesis studies were performed in type I interferon receptor (IFNAR) knockout mice. Blunting the interferon response resulted in robust infectivity, and increased the utility of mice to model ZIKV infections. However, due to the removal of the interferon response, the use of these models impedes full characterization of immune responses to ZIKV-related pathologies. Moreover, IFNAR-deficient models represent severe disease whereas less is known regarding subclinical infections. Investigation of the anti-viral immune response elicited at the maternal-foetal interface is critical to fully understand mechanisms involved in foetal infection, foetal development, and disease processes recognized to occur during subclinical maternal infections. Thus, immunocompetent experimental models that recapitulate natural infections are needed. We have established subclinical intravaginal ZIKV infections in mice and guinea pigs. We found that these infections resulted in: the presence of both ZIKV RNA transcripts and infectious virus in maternal and placental tissues, establishment of foetal infections and ZIKV-mediated CXCL10 expression. These models will aid in discerning the mechanisms of subclinical ZIKV mother-to-offspring transmission, and by extension can be used to investigate other maternal infections that impact foetal development.


β-Lactamase inhibition by avibactam in Mycobacterium abscessus.
Two β-lactams, cefoxitin and imipenem, are part of the reference treatment for pulmonary infections with Mycobacterium abscessus. M. abscessus has recently been shown to produce a broad-spectrum β-lactamase, BlaMab, indicating that the combination of β-lactams with a BlaMab inhibitor may improve treatment efficacy. The objectives of this study were to evaluate the impact of BlaMab production on the efficacy of β-lactams in vitro and to assess the benefit of BlaMab inhibition on the activity of β-lactams intracellularly and in an animal model. We analysed the mechanism and kinetics of BlaMab inactivation by avibactam, a non-β-lactam β-lactamase inhibitor currently in Phase III of development, in combination with ceftazidime for the treatment of serious infections due to Gram-negative bacteria. We then deleted the gene encoding BlaMab to assess the extent of BlaMab inhibition by avibactam based on a comparison of the impact of chemical and genetic inactivation. Finally, the efficacy of amoxicillin in combination with avibactam was evaluated in cultured human macrophages and in a zebrafish model of M. abscessus infection. We showed that avibactam efficiently inactivated BlaMab via the reversible formation of a covalent adduct. An inhibition of BlaMab by avibactam was observed in both infected macrophages and zebrafish. Our data identify avibactam as the first efficient inhibitor of BlaMab and strongly suggest that β-lactamase inhibition should be evaluated to provide improved therapeutic options for M. abscessus infections.


Predicting academic progression for student registered nurse anesthetists.
In order to foster academic progression and improve retention in nurse anesthesia programs, admission selection criteria require attention. With the escalating cost of graduate education coupled with the current economic crisis, efforts by educational leaders to minimize attrition remain pivotal. Selecting potential candidates who are most likely to succeed, aligned with data-driven evidence, offers the greatest potential for academic success for student registered nurse anesthetists. The purpose of this quantitative correlational study was to determine if a relationship existed between admission criteria (grade point average [GPA], science grade point average [SGPA], Graduate Record Examination scores, and critical care experience) and academic progression (current academic status and GPA). Key findings revealed that statistically significant relationships exist between the admission selection criteria and academic progression. Findings also indicated that a combination of the independent variables, specifically the GPA and SGPA, predict academic progression. Further research that includes examination of cognitive and noncognitive admission criteria may offer greater evidence predicting academic performance by student registered nurse anesthetists.


Endemic pulmonary fungal diseases in immunocompetent patients: an emphasis on thoracic imaging.
Systemic endemic mycoses are prevalent in specific geographical areas of the world and are responsible for high rates of morbidity and mortality in these populations, and in immigrants and travelers returning from endemic regions. The most common fungal infections that can affect the lungs of immunocompetent patients include histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, blastomycosis, sporotrichosis, aspergillosis, and cryptococcosis. Diagnosis and management of these diseases remain challenging, especially in non-endemic areas due to the lack of experience. Therefore, recognition of the various radiologic manifestations of pulmonary fungal infections associated with patients' clinical and epidemiologic history is imperative for narrowing the differential diagnosis. Areas covered: This review discusses the clinical and radiological findings of the main endemic fungal diseases affecting the lungs in immunocompetent patients. Specific topics discussed are their etiology, epidemiology, pathogenesis, clinical manifestations, methods of diagnosis, pathology and main imaging findings, especially in computed tomography. Expert commentary: Imaging plays an important role in the diagnosis and management of pulmonary fungal infection and may reveal useful signs. Although definitive diagnosis cannot be made based on imaging features alone, the use of a combination of epidemiologic, clinical and imaging findings may permit the formulation of an adequate differential diagnosis.


Nucleoporin 50 mediates Kcna4 transcription to regulate cardiac electrical activity.
Emerging evidence has demonstrated that nucleoporins (Nups) play a pivotal role in cell-type-specific gene regulation, but how they control the expression and activity of ion channel genes in the heart remains unclear. Here, we show that Nup50, which is localized in the nucleus of cardiomyocytes, selectively induces an increase in the transcription and translation of Kcna4. The Kcna4 gene encodes a K+ voltage-gated channel of shaker-related subfamily member 4 and is essential for regulating the action potential in cardiac membranes. Using immunofluorescence imaging, luciferase assays and chromatin immunoprecipitation assays, we identified that the direct binding of the FG-repeat domain within Nup50 to the proximity of the Kcna4 promoter was required to activate the transcription and subsequent translation of Kcna4. Functionally, Nup50 overexpression increased the currents of KCNA4-encoded Ito,s channels, and reverse knockdown of Nup50 resulted in a remarkable decrease in the amplitude of Ito,s currents in cardiomyocytes. Moreover, a positive correlation between Nup50 and Kcna4 mRNA and protein expression was observed in heart tissues subjected to ischemic insults. These findings provide insights into the homeostatic control of cardiac electrophysiology through Nup-mediated regulation.


[Use of venae comitantes in the creation of arteriovenous fistulas: retrospective evaluation of our experience].
In order to estimate the outcome of arteriovenous fistula (AVF) for hemodialysis, we reviewed our experience in the construction of AVFs using the venae comitantes in patients without an adequate superficial venous vascular territory. The study included 34 patients affected by end-stage renal disease in whom an AVF was created using the deep venous system. In 26 of them we performed an anastomosis between the brachial artery and its vena comitans. Immediate success, defined by the presence of a thrill at the end of the anastomosis, was obtained in 84%, while primary failure of the AVF (immediate postoperative failure) occurred in 3 patients (12%). Early failure, defined as failure within 6 weeks of AVF placement, occurred in 4% of patients. Of the 22 patients with a functioning AVF, 8 (36%) subsequently requested a second operation to bring the fistula to the surface. Some of these involved the placement of synthetic grafts for better accessibility. The primary patency of the AVFs was equal to 64%, while the patency after a second intervention was 91%. Among the 26 AVFs created with venae comitantes, total patency at 50 weeks was 62%. Our experience with the placement of prosthetic grafts draining into the venae comitantes has not provided encouraging results. We believe that for adequate exploitation of venae comitantes it is important to use native veins that have to meet specific anatomical and functional requirements. The creation of an AVF with a native vein, taking advantage of the deep venous system, is feasible under the right circumstances.


Definition of Impulsivity and Related Terms Following Traumatic Brain Injury: A Review of the Different Concepts and Measures Used to Assess Impulsivity, Disinhibition and other Related Concepts.
Impulsivity is a common and debilitating sequela following traumatic brain injury (TBI), but there is no consensual definition or measure to assess this construct. The following review aims to elucidate the differences and resemblances between impulsivity, disinhibition and other related terms following brain injury and the instruments that are commonly used to measure these constructs. To do so, a search through different databases was conducted in order to find articles that mention and define impulsivity, disinhibition, impulse control, regulation deficits, dyscontrol and risky behavior. The concepts that stand out from the literature, the measures used, the similarities, the differences between these concepts are observed. The fit with the UPPS model of impulsivity, according to which impulsivity is a multidimensional concept composed of four distinct dimensions (urgency, perseverance, premeditation and sensation-seeking) is discussed.


Overexpression of Ulk2 inhibits proliferation and enhances chemosensitivity to cisplatin in non-small cell lung cancer.
The aim of the present study was to examine the function of unc-51 like autophagy activating kinase 2 (Ulk2) in non-small cell lung cancer (NSCLC). Western blotting was used to analyze the protein expression of Ulk2 in seven pairs of cancerous and adjacent non-cancerous NSCLC specimens. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was used to determine the mRNA expression of Ulk2 in 20 pairs of tumor and adjacent normal tissues. Two NSCLC cell lines, A549 and H460, were transfected with an Ulk2 overexpression plasmid or empty vector; cell proliferation and chemosensitivity were measured using an MTT assay, and flow cytometry and western blotting were used to evaluate apoptosis. A nude mouse tumorigenesis experiment was used to assess tumor volume in vivo, using A549 cells stably overexpressing Ulk2 and control cells. The protein expression levels of Ulk2 were significantly lower in 6/7 (85.7%) cases of NSCLC compared with in non-cancerous tissues, as determined by western blotting (P<0.05). The mRNA expression levels of Ulk2 were significantly lower in 16/20 (70.0%) NSCLC specimens compared with in non-cancerous tissues, as revealed by RT-qPCR (P<0.05). Overexpression of Ulk2 significantly inhibited the proliferation of A549 and H460 cells (P<0.05) and sensitized the NSCLC cell lines to cisplatin- and etoposide-induced inhibition of proliferation, and to cisplatin-induced apoptosis, with a significant difference identified compared with the control group (P<0.05). Overexpression of Ulk2 significantly increased basal autophagy levels in A549 and H460 cells (P<0.05). Thus, Ulk2-induced enhanced chemosensitivity was suggested to be partly mediated through increased autophagy. The overexpression of Ulk2 significantly suppressed tumor volume in vivo (P<0.05). Overexpression of Ulk2 inhibits cancer cell proliferation and enhances chemosensitivity to cisplatin in NSCLC.


Transient global amnesia following cerebral angiography with non-ionic contrast medium.
Transient global amnesia (TGA) is an uncommon syndrome of recent memory deficit and inability to learn new data, usually resolving within 24 h. Two cases following use of non-ionic contrast media in cerebral angiography are described. The neuroanatomy of memory is reviewed. Possible aetiologies of TGA in relation to cerebral angiography include ischaemia (embolic, arterial spasm), epilepsy that may be primary or tumour-related and direct toxic effects of contrast media.


Contribution of type III interferons to antiviral immunity: location, location, location.
Type I interferons (IFN-α/β) and the more recently identified type III IFNs (IFN-λ) function as the first line of defense against virus infection and regulate the development of both innate and adaptive immune responses. Type III IFNs were originally identified as a novel ligand-receptor system acting in parallel with type I IFNs, but subsequent studies have provided increasing evidence for distinct roles for each IFN family. In addition to their compartmentalized antiviral actions, these two systems appear to have multiple levels of cross-regulation and act coordinately to achieve effective antimicrobial protection with minimal collateral damage to the host.


Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease.
There is evidence that Trigonella foenum-graecum L. (fenugreek), a traditional Chinese herb, and its components are beneficial in the prevention and treatment of diabetes and central nervous system disease. The pharmacological activities of trigonelline, a major alkaloid component of fenugreek, have been more thoroughly evaluated than fenugreek's other components, especially with regard to diabetes and central nervous system disease. Trigonelline has hypoglycemic, hypolipidemic, neuroprotective, antimigraine, sedative, memory-improving, antibacterial, antiviral, and anti-tumor activities, and it has been shown to reduce diabetic auditory neuropathy and platelet aggregation. It acts by affecting β cell regeneration, insulin secretion, activities of enzymes related to glucose metabolism, reactive oxygen species, axonal extension, and neuron excitability. However, further study of trigonelline's pharmacological activities and exact mechanism is warranted, along with application of this knowledge to its clinical usage. This review aims to give readers a survey of the pharmacological effects of trigonelline, especially in diabetes, diabetic complications and central nervous system disease. In addition, because of its pharmacological value and low toxicity, the reported adverse effects of trigonelline in experimental animal models and humans are briefly reviewed, and the pharmacokinetics of trigonelline are also discussed.


[Expression of Notch1 gene in the differentiation of the human embryonic neural stem cells to neurons].
To explore the expression and role of Notch1 gene in the differentiation of the human embryonic neural stem cells to neurons induced by all-trans-retinoic-acid(ATRA). The human embryonic neural stem cells were induced with various concentrations of ATRA(0.5, 1, 5 and 10 mumol/L) in vitro. Immunofluorescence staining was performed after seven days, and neurons were quantified by counting NSE positive cells. Then human embryonic neural stem cells were induced to differentiate with 1 mumol/L ATRA. Total RNA was extracted from the cells before inducing, induced for 3 days, and for 7 days. The expression of Notch1 gene was tested by semi-quantitative RT-PCR. The ratio of neural stem cells to differentiate to neurons was improved greatly by ATRA induction as compared with control group (P<0.01). 1 mumol/L ATRA was the optimal dose for induction of the human embryonic neural stem cell differentiation. The percentage of neurons induced by 1 micromol/L ATRA was (29.20+/-1.09)%. The expression of Notch1 gene decreased significantly after being treated with ATRA(P<0.001). ATRA can greatly increase the percentage of neurons in the course of inducing the human embryonic neural stem cells to differentiate. Notch1 gene is down-regulated when human embryonic neural stem cells differentiate into neurons.


Identification of candidate polymorphisms on stress oxidative and DNA damage repair genes related with clinical outcome in breast cancer patients.
Diverse polymorphisms have been associated with the predisposition to develop cancer. On fewer occasions, they have been related to the evolution of the disease and to different responses to treatment. Previous studies of our group have associated polymorphisms on genes related to oxidative stress (rs3736729 on GCLC and rs207454 on XDH) and DNA damage repair (rs1052133 on OGG1) with a predisposition to develop breast cancer. In the present work, we have evaluated the hypothesis that these polymorphisms also play a role in a patient's survival. A population-based cohort study of 470 women diagnosed with primary breast cancer and a median follow up of 52.44 months was conducted to examine the disease-free and overall survival in rs3736729, rs207454 and rs1052133 genetic variants. Adjusted Cox regression analysis was used to that end. The Kaplan-Meier analysis shows that rs3736729 on GCLC presents a significant association with disease-free survival and overall survival. The polymorphisms rs1052133 on OGG1 and rs207454 on XDH show a trend of association with overall survival. The analysis based on hormonal receptor status revealed a stronger association. The CC genotype on rs207454 (XDH) was significantly associated with lower time of disease free survival (p = 0.024) in progesterone receptor negative (PGR-) patients and rs3736729 (GCLC) was significantly associated with disease free survival (p = 0.001) and overall survival (p = 0.012) in the subgroup of estrogen receptor negative (ER-) patients. This work suggests that unfavorable genetic variants in the rs207454 (XDH) and rs3736729 (GCLC) polymorphisms may act as predictors of the outcome in negative progesterone receptor and negative estrogen receptor breast cancer patients, respectively.


High prevalence of DS-1-like rotavirus infection in Thai adults between 2016 and 2019.
Rotavirus infection is the most common cause of viral diarrhea in infants and young children but uncommon and usually asymptomatic in adults. In the winter of 2017-2018, a large-scale outbreak of rotavirus in both children and adults was reported in Thailand. The current study focused on the prevalence, genotyping, and molecular characterization of rotavirus infections in Thai adults from July 2016 to December 2019. In 2,598 stool samples collected from adult residents of Bangkok (aged #x2265; 15 years) with acute gastroenteritis, rotavirus was detected via real-time RT-PCR analysis of the VP6 gene. G, P and I genotypes were determined by direct sequencing of VP7, VP4, and VP6 genes, respectively. Our results showed 8.7% (226/2,598) of stool samples were positive for rotavirus. The incidence of rotavirus was high during the winter season of 2017-2018 (17.7%) compared to another studied periods (4.5% between July 2016- October 2017 and 2.8% between March 2018- December 2019). Nucleotide sequencing of VP7 and VP4 revealed G3P[8] as the predominant strain (33.2%,75/226), followed by G9P[8] (17.3%,39/226), and G2P[4] (15.0%,34/226). Uncommon G and P combinations were additionally detected at low frequencies. VP6 sequencing was conducted to discriminate I genotype between the Wa and DS-1 genogroup. The unusual DS-1-like G3P[8] strain was most prevalent amomg rotavirus strains detected in this study (29.6%, 67/226), and the corresponding VP7 sequences showed high nucleotide identity with unusual DS-1-like globally circulating strains. Our study demonstrates that rotavirus outbreaks in adults are attributable not only to high prevalence of RV infection but also the unusual DS-like genogroup. The collective findings reinforce the importance of investigating rotavirus diagnosis in adults suffering from acute gastroenteritis and taking appropriate preventive measures.


Identification and Treatment of Adolescents With Perinatal Anxiety and Depression.
Perinatal mood and anxiety disorders (PMAD) are the most common, yet under-diagnosed and undertreated complication of pregnancy, affecting up to 50% of pregnant and parenting teens. PMAD are a global health issue that can have devastating effects on the mental, physical, emotional, developmental health, and social life of the mother, infant, and family. Adolescents present with similar symptoms of PMAD as their adult counterparts, but also experience isolation from their peer group and lack of resources and coping strategies, as well as difficulty sleeping and lack of concentration and ability to focus. Nurses and nurse practitioners are in an ideal position to assess preexisting risk factors for PMAD. The current applied evidence-based article addresses the diagnosis of PMAD, provides a conceptual framework for understanding the intra- and interpersonal dynamics affecting teens with PMAD, and suggests a new screening tool to guide diagnosis. An easy to recall mnemonic for diagnosis and referral (SAIL AHEAD) is proposed. By using the SAIL AHEAD mnemonic, providers will impact adolescents' parenting success and resiliency, thereby enhancing their future success in life. [Journal of Psychosocial Nursing and Mental Health Services, 55(6), 23-29.].


Pubertal development of the pouch and teats in the marsupial Macropus eugenii.
In the female tammar wallaby, Macropus eugenii, which has a highly seasonal breeding pattern, teat eversion and enlargement of the pouch occur at puberty, about 40 weeks after birth. The most obvious sign of puberty is teat eversion: 22 of 23 wild caught, and 23 of 24 captive postpubertal animals had fully everted or everting teats. Full eversion of the teats took on average two to three weeks after puberty. The pouch opening enlarged at puberty, and the rate of enlargement from 2 weeks before puberty to 2 weeks after puberty was significantly greater than the rate before puberty. In a group of pouch young ovariectomized at 5-10 weeks of age, no such changes in either teats or pouch were observed by 46 weeks of age. However, after treatment with oestradiol (0.5 microgram kg-1 body mass), four of five young showed teat eversion within 3-4 weeks. Progesterone (2 mg kg-1) had no effect on inverted teats. In these ovariectomized females oestradiol treatment caused a significant increase in the rate of growth of the pouch opening. During progesterone injections the size of the pouch remained the same. Thus, at puberty the teats and pouch of the tammar wallaby undergo rapid developmental changes and growth. Ovariectomy at an early stage of gonadal differentiation disrupts these normal changes, but treatment of these animals with physiological doses of oestradiol at the age when puberty would normally have occurred can restore teat and pouch maturation. Teat eversion and pouch enlargement can therefore be used as markers for puberty.(ABSTRACT TRUNCATED AT 250 WORDS)


Functional method for assessing oral perceptual skills in children.
An alternative method for assessing oral perceptual skills was developed to address some of the practical limitations of the standard form test. The alternate forms and standard NIH Oral Stereognostic Forms were administered to 182 children. Scores resulting from presentation of standard NIH forms and alternate edibles correlated .76. Suggestions for using the alternate forms for routine oral stereognostic testing are presented.


Mucoepidermoid carcinoma of the airways in a young adult male.
Mucoepidermoid carcinoma (MEC) of the airways is a rare entity most often found in young patients. We present a case of a 23 year old patient with symptoms of pneumonia, which progresses to a pulmonary abscess within a week. Diagnostic work-up reveals an endobronchial obstruction by a pedunculated low grade MEC. A literature review is provided and radiological appearances are described.


School Health Education Program in Pakistan (SHEPP): findings from a feasibility trial in pre-adolescent school children from a lower middle-income country.
The school environment plays an essential role in promoting health education and physical activity for children and adolescents. We aim to assess the feasibility of threefold health education program in children and its potential efficacy on physical activity and diet and cardiometabolic risk factors including blood pressure, body mass index (BMI), and waist circumference. The SHEPP was a parallel group feasibility intervention trial conducted in two schools over 23 months. All children aged 9-11 years enrolled in the schools were included. The SHEPP intervention comprised of health education on healthy lifestyle and physical activity sessions for children, training of teachers, and awareness sessions for parents conducted over 10 months. One school received the intervention of SHEPP while the other school continued routine activity. The primary outcome was the feasibility of SHEPP in terms of recruitment, retention, and treatment fidelity. Secondary outcomes were physical activity levels, dietary intake (of fruits and vegetables), and cardiometabolic risk factors (blood pressure, BMI, and waist circumference (WC)). A total of 1280 preadolescent children were assessed for eligibility and 1191 were found eligible. The overall recruitment n (%) was 982/1191(82.5%) with 505(51.4) from SHEPP intervention school and 477(48.6) in routine activity school. The overall retention rate n (%) at 10-month follow-up was 912/982(92.8), with 465/505(92) in SHEPP intervention school and 447/477(93.7) in routine activity school. In treatment fidelity, 132/144(92) %). Physical activity sessions and all (100%) health education sessions were conducted for each of the twelve classes. Mean (SD) Seven-day Physical activity increased by 134 (196) min in the SHEPP intervention school v 29.8(177) in the routine activity school (P value < 0.001) from baseline to follow-up. Overall, there was an increase in vegetable intake (> 3 serving /day) in SHEPP intervention school of 5.5 to 21.4% from baseline to follow-up compared to 7.5 to 14.9% in routine activity school. The mean change (SD) in systolic blood pressure was 1.3(12) mmHg, 2.2(19.0) mm Hg in in diastolic blood pressure, - 0.09(5.4) kg/m2 in BMI and 6.2 cm in waist circumference in the intervention arm versus - 3.4(11.1) mm Hg in SBP, - 4.3(9.9) mm Hg in DBP, - 0.04((4.6) kg/m2 in BMI, and 3.8 cm in WC in the control arm. We found that intervention using SHEPP is feasible in schools and may help children to adopt a healthy lifestyle as they age by increasing physical activity. However, the potentially beneficial effect on diet, MI, and BP needs further exploration and a longer follow-up, more specifically at the juncture of teenage and adulthood. NCT03303287.