Biotransformation of water lettuce (Pistia stratiotes) to biohydrogen by Rhodopseudomonas palustris.
Aim of the paper was to assess the feasibility of producing hydrogen as a biofuel by photofermentation of fermented water lettuce (Pistia stratiotes L.) waste biomass, after a nitrogen-stripping treatment. A natural (42OL) and an engineered strain (CGA676, with low-ammonium sensitivity) of Rhodopseudomonas palustris were used for producing hydrogen. The stripping procedure was highly effective for ammonium removal, with an acceptable selectivity (91% of ammonium was removed; only 14% of total organic acids were lost). Both strains were able to produce hydrogen only in the nitrogen-stripped substrate. The natural strain R. palustris 42OL showed a higher Biochemical Hydrogen Potential (1224 ml l-1 vs 720 ml l-1 ; 50·0 mol m-3 vs 29·4 mol m-3 ), but at a lower rate (5·6 ml l-1 h-1 vs 7·3 ml l-1 h-1 ; 0·23 mol m-3 h-1 vs 0·29 mol m-3 h-1 ) than strain CGA676. Water lettuce waste biomass can be used for biofuel production, after hydrolization, fermentation and nitrogen stripping. The investigation on novel, low cost and sustainable biomasses as feedstocks for biofuel production is a priority. Aquatic plants do not compete for arable land. Moreover, water lettuce is a floating and invasive weed, thus its biomass must be harvested when detrimental, and can now be biotransformed in clean hydrogen.


Stretchable Self-Healing Plastic Polyurethane with Super-High Modulus by Local Phase-Lock Strategy.
In this work, a multiblock polyurethane (PU-Im) consisting of polyether and polyurethane segments with imidazole dangling groups is demonstrated, which can further coordinate with Ni2+ . By controlling the ligand content and metal-ligand stoichiometry ratio, PU-Im-Ni complex with vastly different mechanical behavior can be obtained. The elastomer PU-2Im-Ni has extraordinary mechanical strength (61MPa) and excellent toughness (420 MJ m-3 ), but the plastic PU-4Im-Ni exhibits super-high modulus (515 MPa), strength (63 MPa), and good stretchability (≈800%). The metal-ligand interaction between polyurethane segments and Ni2+ is proved by Raman spectra, dynamic mechanical analysis (DMA), and transmission electron microscopy (TEM). The polyurethane segments domain formed by microphase separation is dynamically "locked" by Ni2+ coordinated with imidazole, revealing a local phase-lock effect. The phase-locking hard domains reinforce the PU-Im-Ni complex and maintain stimuli-responsive self-healing ability, while the free polyether segments provide stretchability. Primarily, the water environment with plasticization effect serves as an effective and eco-friendly self-healing approach for PU-Im-Ni plastic. With the excellent mechanical performance, thermal/aquatic self-healing ability, and unique damping properties, the PU-Im-Ni complexes show potential applications in self-healing engineering plastic and cushion protection fields.


Flotation rest as a smoking intervention.
The present study is an attempt to produce smoking cessation or reduction in persons who smoke cigarettes heavily but are motivated to stop. It makes use of the floating environment as an intervention, coupled with messages designed to shape attitudinal change. Subjects were followed up for twelve months post-intervention. Reduction at 12 month follow-up compares favorably with other interventional techniques, and floats of longer duration appear to be a more effective intervention than shorter floats. Messages did not add to effects found. Control subjects reduced their smoking more than the experimental subjects, suggesting that the procedures used on them were actually more effective interventions.


Influence of different implantation techniques on AV valve competence after orthotopic heart transplantation.
About a decade after the introduction of the bicaval and pulmaonary venous heart transplantation technique a reduction of tricuspid and mitral valve incompetence compared to the standard technique by Lower and Shumway is still discussed controversially. We used this technique regularly since the year 1993 and report about our 10 years experience. A total of 297 patients were transplanted at our institution between 1989 and 2003, 158 with the standard and 139 in the total orthotopic technique (TOHT). Ninety-four of the standard and 72 of the TOHT group were followed up as outpatients and were examined with right-heart catheterisation and trans-thoracic echocardiography. Patients in both groups were similar in demographic data. Right heart catheterisation showed no statistical significant differences between the two groups. The left atrium was significantly enlarged in the standard group. The TOHT group showed a significant reduction of tricuspid regurgitation in 5-year follow up echocardiography. This study showed excellent long-term survival rates for both groups. The significant reduction of left atrial size and atrio-ventricular valve regurgitation in the TOHT group might have important impact on the long-term preservation of cardiac function. Total orthotopic heart transplantation with bicaval and pulmonary venous anastomosis should be preferred for heart transplantation.


Identification and Functional Analysis of a Novel Hydrophobic Protein VdHP1 from Verticillium dahliae.
Verticillium dahliae could cause destructive vascular wilt disease on hundreds of plant species around the world, including cotton. In this study, we characterized the function of a hydrophobin gene VdHP1 in pathogen development and pathogenicity. Results showed that VdHP1 could induce cell death and activate plant immune responses. The VdHP1 deletion mutants (ΔVdHP1) and the complement mutants (C-ΔVdHP1) were obtained by the homologous recombination method. The VdHP1 deletion mutants exhibited increased hydrophilicity, inhibited microsclerotial formation, and reduced spore smoothness. In addition, the deletion mutants were more sensitive to NaCl, while relatively insensitive to KCl and sorbitol. Mutants also had greater resistance to Congo red, UV radiation, and high temperature, which suggested that ΔVdHP1 strains have stronger resistance to abiotic stress in general. Different carbon source assays showed that the utilization ability of skim milk, cellulose, and starch was greatly enhanced in ΔVdHP1, compared with that of WT and complemented strains. Furthermore, VdHP1 did not affect mycelium penetration on cellophane but contributed to mycelium growth on surface of the living plant cells. The pathogenicity test found that the crude toxin content, colonization, and dispersal of ΔVdHP1 was significantly increased compared with the WT and complementary strains. In addition, cotton seedlings showed more severe wilting symptoms after inoculation with ΔVdHP1 strains. These results suggested that the hydrophobin VdHP1 negatively regulated the virulence of V. dahliae, and played an important role in development, adaptability, and pathogenicity in V. dahliae, which maybe provide a new viewpoint to further understand the molecular mechanisms of pathogen virulence. IMPORTANCE Verticillium dahliae is a soilborne fungal pathogen that causes a destructive vascular disease on a large number of plant hosts, resulting in great threat to agricultural production. In this study, it was illustrated that the hydrophobin VdHP1 could induce cell death and activate plant immune responses. VdHP1 affected the hydrophobicity of V. dahliae, and negatively regulated the strains resistant to stress, and the utilization ability of different carbon sources. In addition, VdHP1 did not affect mycelium penetration on cellophane but contributed to mycelium growth on surface of the living plant cells. The VdHP1 gene negatively regulated the total virulence, colonization, and dispersal of V. dahliae, with enhanced pathogenicity of mutant strains in this gene. These results suggested that the hydrophobin VdHP1 played an importance in development, adaptability, and pathogenicity in V. dahliae, and would provide a new viewpoint to further understand the molecular mechanisms of pathogen virulence.


Emerging bilingualism: dissociating advantages for metalinguistic awareness and executive control.
The present studies revealed different factors associated with the reported advantages found in fully bilingual children for metalinguistic awareness and executive control. Participants were 100 children in Study 1 and 80 children in Study 2 in the process of becoming bilingual by attending immersion programs. In both studies, level of proficiency in the language of testing was related to performance on metalinguistic tasks and length of time in the immersion program was related to performance on executive control tasks. This dissociation is consistent with models of lifespan development that distinguish between representational structure and executive control.


Cell proliferation during early diencephalon development in Alligator.
Using immunocytochemical methodology, cell proliferation was investigated in Alligator during early diencephalon development. These results were compared with cell proliferation during early hindbrain formation in this same species using identical techniques. The pattern of cell proliferation in the diencephalon differed from that observed in the rhombencephalon. If cell proliferation is a factor influencing brain development, then the diencephalon of Alligator may be built differently from the hindbrain.


Kinetic studies on the enzymes conjugating bile acids with taurine and glycine in bovine liver.
Synthesis of glyco- or tauro-cholate from choloyl-CoA and the respective amino acid is shown to be catalysed by the soluble fraction of liver cells. Kinetic evidence supports the conclusion that there are separate enzymes for the synthesis of glycocholate and taurocholate. The kinetic parameters of these enzymes were determined.


[Pulmonary edema secondary to acute obstruction of the upper airways. Apropos of a case of immediate recovery].
The AA. inform on the case of a girl, 13, carrying an aortic prosthesis who some hours after the removal of a laryngeal dilator had an asphyctic syndrome during a meal. The emergency being overcome an acute pulmonary edema could be diagnosed without either objective valvular or left ventricular dysfunctions. In spite of the prior heart pathology the reporters belief in the coincidence of the case displayed with a pulmonary edema following the acute obstruction of the upper respiratory tract. They review the proposed physiopathological hypothesis as well as the Spanish literature upon the subject.


Finite element analysis of the effect of loading curve shape on brain injury predictors.
Prediction of traumatic and mild traumatic brain injury is an important factor in managing their prevention. Currently, the prediction of these injuries is limited to peak linear and angular acceleration loading curves derived from laboratory reconstructions. However it remains unclear as to what aspect of these loading curves contributes to brain tissue damage. This research uses the University College Dublin Brain Trauma Model (UCDBTM) to analyse three distinct loading curve shapes meant to represent different helmet loading scenarios. The loading curves were applied independently in each axis of linear and angular acceleration and their effect on currently used predictors of TBI and mTBI was examined. Loading curve shape A had a late time to peak, B an early time to peak and C had a consistent plateau. The areas under the curve for all three loading curve shapes were identical. The results indicate that loading curve A produced consistently higher maximum principal strains and Von Mises stress than the other two loading curve types. Loading curve C consistently produced the lowest values of maximum principal strain and Von Mises stress, with loading curve B being lowest in only 2 cases. The areas of peak Von Mises stress and Principal strain also varied depending on loading curve shape and acceleration input.


Central administration of oxytocin differentially increases yawning, penile erections and scratching in high- (HY) and low-yawning (LY) sublines of Sprague-Dawley rats.
Central administration of oxytocin has been shown to induce yawning, penile erection, grooming and scratching. Yawning and penile erections are due to activation of oxytocinergic neurons in the paraventricular nucleus of the hypothalamus. We selectively bred two sublines from Sprague-Dawley rats, one with a high-yawning frequency (HY) of 20yawns/h, and one with a low-yawning (LY) frequency of 2yawns/h. The aim of the current study was to analyze the behavioral effects of centrally-administered oxytocin [15ng-10μg; intracerebroventricularly (i.c.v.)] on yawning, penile erections, grooming and scratching in adult male rats from both sublines. Oxytocin produced a dose-dependent increase in yawning and penile erection frequencies and this effect was significantly higher in the HY, compared to the LY, subline. However, the number of oxytocin-induced scratching bouts was significantly higher in the LY, compared to the HY group. In conclusion, these sublines represent a suitable model for detailed analysis of behavior induced by oxytocin and other neuropeptides in animals with different spontaneous expression of behavioral traits.


Process evaluation of a tailored work-related support intervention for patients diagnosed with gastrointestinal cancer.
To perform a process evaluation of a tailored work-related support intervention for patients diagnosed with gastrointestinal cancer. The intervention comprised three tailored psychosocial work-related support meetings. To outline the process evaluation of this intervention, we used six key components: recruitment, context, reach, dose delivered, dose received and fidelity. Data were collected using questionnaires, checklists and research logbooks and were analysed both quantitatively and qualitatively. In total, 16 hospitals, 33 nurses and 7 oncological occupational physicians (OOPs) participated. Analysis of the six key components revealed that the inclusion rate of eligible patients was 47%. Thirty-eight intervention patients were included: 35 actually had a first meeting, 32 had a second and 17 had a third. For 31 patients (89%), the first meeting was face to face, as per protocol. However, in only 32% of the cases referred to support type A (oncological nurse) and 13% of the cases referred to support type B (OOP), the first meeting was before the start of the treatment, as per protocol. The average duration of the support type A meetings was around the pre-established 30 min; for the OOPs, the average was 50 min. Protocol was easy to follow according to the healthcare professionals. Overall, the patients considered the intervention useful. This study has shown that the strategy of tailored work-related support is appreciated by both patients and healthcare professionals and applicable in clinical practice. The intervention was appreciated by patients; however, whether the timing of the work-related support was adequate (i.e. before treatment was started) requires further research. NTR5022.


Response of an insect herbivore to host plants grown in carbon dioxide enriched atmospheres.
Rising atmospheric carbon dioxide concentration is expected to increase plant productivity, but little evidence is available regarding effects on insect feeding or growth. Larvae of the soybean looper, a noctuid moth, were fed leaves of soybean plants grown under three carbon dioxide regimes (350, 500 and 650 μl·l-1). Larvae fed at increasingly higher rates on plants from elevated carbon dioxide atmospheres: 30% greater on leaves from the 650 μl·l-1 treatment than on leaves from the 350 μl·l-1 treatment. When variation in larval feeding was related to the leaf content of nitrogen and water, there was no significant remaining effect of carbon dioxide treatment. The principal effect on herbivores of increasing the carbon supply of leaves appeared to be reduction of leaf nutrient concentration. This study suggests that feeding by herbivores on the leaves of C3 plants may increase as the level of atmospheric carbon dioxide rises.


Effects of a high dose intravenous bolus amiodarone in patients with atrial fibrillation and a rapid ventricular rate.
Amiodarone, given as intravenous bolus has not yet been studied in patients with atrial fibrillation and a high ventricular rate. One hundred consecutive patients with atrial fibrillation and a ventricular rate above 135 bpm were randomized to receive either 450 mg amiodarone or 0.6 mg digoxin given as a single bolus through a peripheral venous access. If the ventricular rate exceeded 100 bpm after 30 min, another 300 mg amiodarone or 0.4 mg digoxin were added. Primary endpoints of the study were the ventricular rate and the occurrence of sinus rhythm after 30 and 60 min. Secondary endpoints were blood pressure during the first hour after drug administration, and safety regarding drug induced hypotension, and phlebitis at the infusion site. Baseline heart rate was 144+/-19 in the amiodarone group and 145+/-15 in the digoxin group (p=0.72). Following amiodarone, heart rate was 104+/-25 after 30 min compared to 116+/-23 in the digoxin group (p=0.02) and 94+/-22 versus 105+/-22 after 60 min (p=0.03). After 30 min, sinus rhythm was documented in 14 (28%) patients following amiodarone compared to 3 (6%) patients in the digoxin group (p=0.003), and after 60 min in 21 (42%) versus 9 (18%) patients (p=0.012). Asymptomatic hypotension was observed in 4 amiodarone treated patients, and superficial phlebitis in 1 patient. Amiodarone, given as an intravenous bolus is relatively safe and more effective than digoxin for heart rate control and conversion to sinus rhythm in patients with atrial fibrillation and a rapid ventricular rate.


Cancer screening in the United States, 2012: A review of current American Cancer Society guidelines and current issues in cancer screening.
Each year the American Cancer Society (ACS) publishes a summary of its recommendations for early cancer detection, a report on data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, current ACS cancer screening guidelines are summarized, as are the latest data on the use of cancer screening from the National Health Interview Survey.


Auditory Sensitivity and Masking Profiles for the Sea Otter (Enhydra lutris).
Sea otters are threatened marine mammals that may be negatively impacted by human-generated coastal noise, yet information about sound reception in this species is surprisingly scarce. We investigated amphibious hearing in sea otters by obtaining the first measurements of absolute sensitivity and critical masking ratios. Auditory thresholds were measured in air and underwater from 0.125 to 40 kHz. Critical ratios derived from aerial masked thresholds from 0.25 to 22.6 kHz were also obtained. These data indicate that although sea otters can detect underwater sounds, their hearing appears to be primarily air adapted and not specialized for detecting signals in background noise.


Immunocompromised women are at increased risk of having HPV detected and developing HPV-related diseases such as genital warts, anogenital dysplasia, and cancer. This review aims to summarize the current literature regarding the immunogenicity of the HPV vaccine in immunocompromised women and to discuss whether HPV vaccination may be able to reduce the risk of cervical dysplasia and cancer. HPV vaccination induces an immune response in these women; however, it is unknown whether vaccination is effective in reducing the risk of cervical dysplasia and cancer. Further research is needed.


Risk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies.
The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-cell-depleting (anti-CD20) therapies and severity, while others fail to observe an association. Most existing studies are limited by a reliance on 'numerator' data (i.e., COVID-19 cases) only. To assess the risks of COVID-19 by DMT, this study aimed to assess both 'numerator' (patients with SARS-CoV-2 infection) and 'denominator' data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity. We systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (dimethyl fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clinical symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator. We identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (n = 173; 75.2%) or suspected (n = 57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19. Analysis of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.


Cone-mediated retinal function in cats during development.
Cone electroretinograms (ERGs) were recorded in kittens from 25 to 150 days of age and in adult cats. B-wave amplitudes in kittens between 25 and 94 days of age were either within the adult range or greater than adult responses. After about 100 days, all kittens had adult-like amplitudes. Cone b-wave implicit time was markedly prolonged at the earliest ages tested and only after 80 days was the timing like that in adult cats. Amplitude and timing of 40-Hz flicker ERGs confirmed the single flash cone ERG data. Critical flicker fusion frequency was mature by 74 days of age. These findings, taken together with previous results, indicate that there are differences in the time course of development of cone- and rod-mediated retinal function in the cat.


Biological properties of synthetic glycoconjugate mimics of heparin comprising different molecular spacers.
The in vitro antithrombotic activity of synthetic glycoconjugates I and II, comprising a flexible polyethylene glycol type and a rigid polyglucose type spacer, respectively, are compared to heparin.


Optimizing outcomes in bariatric surgery: outpatient laparoscopic gastric bypass.
Roux-en-Y gastric bypass (RYGB) is an effective treatment of severe obesity and one of the fastest growing surgical procedures in the United States. A single institution prospective database of patients undergoing outpatient laparoscopic (lap) RYGB over a 3-year period was reviewed. Study end points included hospital discharge within 23 hours, 30-day hospital readmission rate, early (<30 day) and late complication rates, and 30-day perioperative mortality. Variables assessed included surgeon experience, patient demographics, comorbidities, operative time, Roux limb pathway, intraoperative steroid bolus, and use of dexmedetomidine. Two thousand consecutive patients undergoing outpatient lap RYGB were identified, and 84% (n = 1669) were discharged within 23 hours. Of these, 1.7% (n = 34) were readmitted within 30 days. The overall early and late complication rates were 1.9% (n = 38) and 4.3% (n = 86), respectively. The 30-day mortality rate was 0.1% (n = 2), and neither patient was discharged before death. Univariate analysis demonstrated surgeon experience (<50 cases), age (<56 years), body mass index (<60 kg/m), weight (400 lbs), comorbidities (<5), and intraoperative steroid bolus as predictive of successful outpatient discharge. Multivariate analysis revealed surgeon experience, comorbidities, body mass index, and steroid bolus as predictive variables. These data suggest that outpatient lap RYGB can be performed with acceptable perioperative complication rates, hospital readmission, and mortality rates. Surgeon experience, careful patient selection, and the use of intraoperative steroid bolus predicted optimal patient outcomes.


The effect of fluorocarbon emulsion on 24-hour canine heart preservation by coronary perfusion.
This study was designed to evaluate the effects of fluorocarbon emulsion as an oxygen carrier in myocardial preservation. The hearts were preserved for 24 hours by coronary perfusion with either oxygenated crystalloid cardioplegic solution (group C) or crystalloid cardioplegic solution with fluorocarbon added (group FC). The perfusion pressure was kept at 20 mm Hg, and myocardial temperature was maintained at 4 degrees C. Group FC demonstrated better recovery in developed pressure and maximum rate of rise of left ventricular pressure compared with group C. The postpreservation end-diastolic pressure in group C increased significantly compared with the baseline value (value obtained before preservation). On the other hand, group FC showed no significant increase of end-diastolic pressure after preservation. Group FC released a significantly lower level of creatine kinase into its perfusate than did group C. Ultrastructural changes after preservation in group C showed severe ischemic injury, but there was no evidence of ischemic injury in group FC. The use of fluorocarbon emulsion proved beneficial to myocardial protection in long-term preservation of canine hearts.


MicroRNA-128a-induced apoptosis in HTR-8/SVneo trophoblast cells contributes to pre-eclampsia.
Pre-eclampsia (PE) can endanger the survival of the mother and fetus. Currently, the pathogenesis of PE is not completely understood and no fundamental therapeutics are available. The present study was performed to determine the function of miR-128a in HTR-8/SVneo trophoblast cells and to ascertain its underlying role in the pathogenesis of PE. We investigated the function of miR-128a in HTR-8/SVneo cells by overexpressing. We analyzed the apoptosis of HTR-8/SVneo cells by performing apoptosis assays and measured the loss of mitochondrial membrane potential (Δym), the generation of reactive oxygen species (ROS) and caspase activity. In addition, miR-128a target genes were predicted. Using computer-based programs, we identified Bax as a direct target of miR-128a. In the apoptosis assays of HTR-8/SVneo cells, miR-128a decreased the Δψm, depleted ATP levels and increased ROS generation, cytochrome c release as well as caspase activation. Further studies showed that miR-128a induced the apoptosis of HTR-8/SVneo cells by down-regulating Bax through the mitochondrial apoptosis pathway. miR-128a is an up-regulated miRNA in patient with PE. Our study demonstrated that the miR-128a-induced apoptosis of HTR-8/SVneo cells may contribute to PE and miR-128a may be a novel potential therapeutic target for PE.


Superimposition of nutcracker syndrome in a hematuric child with idiopathic hypercalciuria and urolithiasis.
We report a 5-year-old girl with idiopathic hypercalciuria who developed gross hematuria and left flank pain despite normalization of calciuria, a renal stone, and microscopic hematuria. She was found to have nutcracker syndrome by renal Doppler ultrasound, which revealed the significant differences of the peak blood flow velocities in the two portions of the left renal vein.


Ocular hypertension. A 15-year follow-up.
A group of 55 subjects with ocular hypertension were followed-up after 15 years. They were detected at a glaucoma screening on the island of Falster between 2031 volunteer blood donors, and they had an applanation pressure of greater than or equal to 20 mmHg in one or both eyes. All the subjects were traced. Nine have died, all from general causes, and one of the deceased subjects was treated for simple glaucoma. Of the remaining 46 living subjects, 3 developed glaucomatous visual field defects despite treatment. In another 4 subjects anti-glaucoma treatment was felt to be indicated. Of the non-treated 39 living subjects, 20 had a decreased applanation pressure, well below 20 mmHg, and 19 had an unaltered applanation pressure. We found that neither the common blood groups nor a water provocative test performed in 1962 were of any help in predicting glaucomatous visual field defects. Central corneal thickness measurements performed in 1977 could not allocate the subjects to the groups simple glaucoma, applanation pressure greater than 20 mmHg or less than or equal to 20 mmHg.


A pH‑responsive hyaluronic acid nano‑vehicle co‑encapsulating doxorubicin and all‑trans retinoic acid for the inhibition of hepatic stellate cell‑induced tumor growth and metastasis.
All‑trans retinoic acid (ATRA) has been implicated in the differentiation of hepatic stellate cells (HSCs). In the present study, the liver‑targeting hyaluronic acid micelles (ADHG) were prepared for co‑delivery of ATRA and doxorubicin (DOX) to block the HSC‑hepatoma interrelation. To simulate the tumor microenvironment, an in vitro dual‑cell model and an in vivo co‑implantation mouse model were established for anticancer studies. The experimental methods involved the MTT assay, wound‑healing assay, cellular uptake, flow cytometry and and in vivo antitumor study. The results revealed that the HSCs in the research models notably promoted tumor proliferation and migration. Furthermore, ADHG were readily internalized by cancer cells and HSCs simultaneously, and widely distributed in cancer regions. The in vivo antitumor studies demonstrated that ADHG could notably decrease HSC activation and extracellular matrix deposition, as well as constrain tumor growth and metastasis. Therefore, ATRA could facilitate DOX‑induced anti‑proliferation and anti‑metastasis effects, and ADHG are a promising nano‑sized formulation for the combination therapy of hepatocellular carcinoma.


An alternative approach to study irrotational periodic gravity water waves.
We are concerned here with an analysis of the nonlinear irrotational gravity water wave problem with a free surface over a water flow bounded below by a flat bed. We employ a new formulation involving an expression (called flow force) which contains pressure terms, thus having the potential to handle intricate surface dynamic boundary conditions. The proposed formulation neither requires the graph assumption of the free surface nor does require the absence of stagnation points. By way of this alternative approach we prove the existence of a local curve of solutions to the water wave problem with fixed flow force and more relaxed assumptions.


Nonparametric spectral methdods for multivariate spatial and spatial-temporal data.
We propose computationally efficient methods for estimating stationary multivariate spatial and spatial-temporal spectra from incomplete gridded data. The methods are iterative and rely on successive imputation of data and updating of model estimates. Imputations are done according to a periodic model on an expanded domain. The periodicity of the imputations is a key feature that reduces edge effects in the periodogram and is facilitated by efficient circulant embedding techniques. In addition, we describe efficient methods for decomposing the estimated cross spectral density function into a linear model of coregionalization plus a residual process. The methods are applied to two storm datasets, one of which is from Hurricane Florence, which struck the souteastern United States in September 2018. The application demonstrates how fitted models from different datasets can be compared, and how the methods are computationally feasible on datasets with more than 200,000 total observations.


A Novel Capacitance-Based In-Situ Pressure Sensor for Wearable Compression Garments.
This paper pertains to the development & evaluation of a dielectric electroactive polymer-based tactile pressure sensor and its circuitry. The evaluations conceived target the sensor's use case as an in-situ measurement device assessing load conditions imposed by compression garments in either static form or dynamic pulsations. Several testing protocols are described to evaluate and characterize the sensor's effectiveness for static and dynamic response such as repeatability, linearity, dynamic effectiveness, hysteresis effects of the sensor under static conditions, sensitivity to measurement surface curvature and temperature and humidity effects. Compared to pneumatic sensors in similar physiological applications, this sensor presents several significant advantages including better spatial resolution, compact packaging, manufacturability for smaller footprints and overall simplicity for use in array configurations. The sampling rates and sensitivity are also less prone to variability compared to pneumatic pressure sensors. The presented sensor has a high sampling rate of 285 Hz that can further assist with the physiological applications targeted for improved cardiac performance. An average error of ± 5.0 mmHg with a frequency of 1-2 Hz over a range of 0 to 120 mmHg was achieved when tested cyclically.


New electrical impedance methods for the in situ measurement of the complex permittivity of anisotropic skeletal muscle using multipolar needles.
This paper provides a rigorous analysis on the measurement of the permittivity of two-dimensional anisotropic biological tissues such as skeletal muscle using the four-electrode impedance technique. The state-of-the-art technique requires individual electrodes placed at the same depth in contact with the anisotropic material, e.g. using monopolar needles. In this case, the minimum of measurements in different directions needed to estimate the complex permittivity and its anisotropy direction is 3, which translates into 12 monopolar needle insertions (i.e. 3 directions × 4 electrodes in each direction). Here, we extend our previous work and equip the reader with 8 new methods for multipolar needles, where 2 or more electrodes are spaced along the needle's shaft in contact with the tissue at different depths. Using multipolar needles, the new methods presented reduce the number of needle insertions by a factor of 2 with respect to the available methods. We illustrate the methods with numerical simulations and new experiments on ex vivo ovine skeletal muscle (n = 3). Multi-frequency longitudinal and transverse permittivity data from 30 kHz to 1 MHz is made publicly available in the supplementary material. The methods presented here for multipolar needles bring closer the application of needle electrical impedance to patients with neuromuscular diseases.


Polymorphism in APOB associated with increased low-density lipoprotein levels in both genders in the general population.
Rare mutations in APOB cause hypercholesterolemia. Whether common polymorphisms in APOB have similar effects remains controversial. We tested the hypothesis that the APOB 7673C>T polymorphism (T2488T) is associated with variation in low-density lipoprotein (LDL) levels and with risk of ischemic heart disease (IHD), ischemic cerebrovascular disease (ICVD), and total mortality in the general population. The design was a cohort study with 22-yr follow-up (166,232 person years) and two case-control studies, The Copenhagen City Heart Study. The study was performed within the Danish general population and at a university hospital. The study was comprised of 9185 individuals from the general population, 2157 patients with IHD, and 378 patients with ICVD. The main outcome measures were lipids, lipoproteins, apolipoproteins (apo), IHD, ICVD, and total mortality. Genotype was associated with increases in total cholesterol (women/men), LDL cholesterol, and apoB of 0.20/0.26 mmol/liter (3.3%/4.4%), 0.22/0.28 mmol/liter (5.9%/7.8%), and 5.0/5.6 mg/dl (5.9%/6.7%) in TT vs. CC homozygotes, respectively. These results were consistent over time. Despite this, the 7673C>T polymorphism was not associated with risk of IHD, ICVD, or total mortality prospectively or in case-control studies. The APOB 7673C>T polymorphism is associated with moderate increases in total cholesterol, LDL cholesterol, and apoB in both genders in the general population, but not with risk of IHD, ICVD, or total mortality.


Acupuncture for lateral epicondylitis: A prisma-compliant protocol for a systematic review and meta-analysis of randomized controlled trials.
Acupuncture has been widely used for relieving pain associated with musculoskeletal disorders, such as lateral epicondylitis. Although the effect of acupuncture on pain has been demonstrated in previous reviews, it is still under debate. This study is aimed at evaluating the efficacy of acupuncture to treat lateral epicondylitis and establishing the evidence systematically. Nine databases will be searched from their inception to May 2020 without language or publication status restrictions, including 3 English databases (MEDLINE, Embase, the Cochrane Central Register of Controlled Trials), 5 Korean databases (Korean Medical Database, KoreaMed, Korean Studies Information Service System, Research Information Service System, Oriental Medicine Advanced Searching Integrated System), and 1 Chinese database (China Knowledge Network Database). Only randomized controlled trials will be included. Pain intensity will be considered as the primary outcome. Secondary outcomes will include the grip strength, total effective rate, and adverse events. Two independent researchers will perform the study selection, data extraction, and quality assessment. The methodological quality of the identified studies will be assessed using the Cochrane Collaboration's risk-of-bias tool. In the meta-analysis, continuous data will be expressed as mean and 95% confidence interval, and dichotomous data will be expressed as risk ratio and 95% confidence interval. The results of this study will be submitted to a peer-reviewed journal for publication. The results of this study would provide the evidence of whether acupuncture is effective for lateral epicondylitis. PROSPERO CRD42020186824.


Post-gastric-bypass hypoglycemia successfully treated with alpha-glucosidase inhibitor therapy.
To review the effectiveness of alpha-glucosidase inhibitor (AGI) therapy in the treatment of hypoglycemia after Roux-en-y gastric surgery. Retrospective case review. Four patients who previously underwent Roux-en-y gastric bypass were evaluated because of severe symptomatic postprandial hypoglycemia that was unresponsive to a low-carbohydrate diet. Mixed-meal testing confirmed hyperinsulinemia. Other causes of hypoglycemia were ruled out by a combination of clinical examination, endocrine testing, and computed tomography imaging. Symptomatic hypoglycemia resolved in all 4 patients after AGI therapy was started. One patient could not tolerate long-term therapy because of a rash. The other 3 patients were followed for between 5 and 48 months and remained free of symptomatic postprandial hypoglycemia. AGI therapy is effective in the long-term treatment of post-Roux-en-y hypoglycemia in patients unresponsive to a low-carbohydrate diet. To our knowledge, this is the first report documenting the long-term usefulness of this therapy in a series of patients.


Protein Phosphatase 2a Inhibits Gastric Cancer Cell Glycolysis by Reducing MYC Signaling.
Aerobic glycolysis, also known as the Warburg effect, has emerged as a hallmark of cancer and is associated with tumor progression and unfavorable clinical outcomes in cancer patients. PP2A is a highly conserved eukaryotic serine/threonine protein phosphatase that functions as a tumor suppressor in a variety of human cancers. However, the relationship between PP2A and the Warburg effect in gastric cancer has yet to be fully understood. In this study, the expression profile of two endogenous inhibitors of PP2A, SET and CIP2A, in gastric cancer, were analyzed by real-time quantitative polymerase chain reaction. Loss-of-function and gain-of-function studies were performed to investigate the roles of PP2A in gastric cancer cell proliferation and glycolysis. Cell biological, molecular, and biochemical approaches were employed to uncover the underlying mechanisms. The results showed that SET and CIP2A were overexpressed in gastric cancer and associated with a decreased PP2A activity. Pharmacological activation of PP2A with FTY-720 and DT-061 in two gastric cancer cell lines significantly reduced gastric cancer cell proliferation and glycolytic ability. Importantly, inhibition of PP2A activity by genetic silencing of PPP2R5A resulted in a growth advantage, which can be largely compromised by the addition of the glycolysis inhibitor 2-Deoxy-D-glucose, suggesting a glycolysis-dependent effect of PP2A in gastric cancer. Mechanistically, the well-known transcription factor and glycolysis regulator c-Myc was discovered as the functional mediator of PP2A in regulating cell glycolysis. Ectopic expression of a phosphorylation-mutant c-Myc resistant to PP2A (MycT58A) restored the inhibitory effect of FTY-720 and DT-061 on lactate production and glucose uptake. Furthermore, there was a close association between SET and CIP2A expression and c-Myc gene signatures in gastric cancer samples. Collectively, this study provides strong evidence of the involvement of PP2A in the Warburg effect and indicates that it could be a novel antitumor strategy to target tumor metabolism in gastric cancer.


Ovarian cyst aspiration and the outcome of in vitro fertilization.
This study was designed to ascertain whether any benefit would be derived from aspirating ovarian cysts identified before ovarian stimulation in patients undergoing in vitro fertilization. Thirty-seven patients who had ovarian cysts were categorized into two groups: group A (n = 14) with baseline ovarian cysts and group B (n = 23) with ovarian cysts that developed during pituitary suppression with the gonadotropin-releasing hormone analog. Each group was prospectively randomized into two subgroups depending on whether the ovarian cysts were aspirated or not. In group A, there was a significantly greater number of follicles and oocytes in the ovaries in which cysts were aspirated. However, there was no significant difference in the total number of follicles, oocytes retrieved and fertilized, or in the final outcome. In group B, there was no significant difference in folliculogenesis between the aspirated and nonaspirated subgroups. These observations suggest that the presence of a baseline ovarian cyst may reduce folliculogenesis but do not support routine cyst aspiration if the patient has two functional ovaries.


Analysis on the interaction between post-spliced introns and corresponding protein coding sequences in ribosomal protein genes.
Many experiments show that intron loss/gain can influence many stages of mRNA metabolism. However, in the current work, post-spliced introns are not considered directly. Here, the optimal matched regions between introns and their protein coding sequences in ribosomal protein genes are intensively investigated by using the improved Smith-Waterman local alignment software. In introns, it is found that optimal matched regions are located in the central non-conserved regions, and their distribution characteristics are different from each intron group. We find two optimal matched regions in long introns, and the former one is more conservative than the latter one. We also find only one optimal matched region in short introns. In protein coding sequences, there are some optimal matched regions and forbidden regions, especially two conserved forbidden regions located at about 10% and 80% in the length of protein coding sequences. The forbidden regions may be potential protein-binding regions. Match rates of most optimal matched segments range among 65% and 75% and they belonged to weak match. The interaction between post-spliced introns and corresponding protein coding sequences may play a key role in gene expression.


Vascular endothelial cell-cardiac myocyte crosstalk in achieving a balance between energy supply and energy use.
In isolated perfused hearts, endothelial cells in the coronary arterial vascular system release substances that can alter the contractility of the cardiac myocytes. There are at least two different substances, one that increases and another that decreases the contractility of cardiac myocytes. The rate of release of these endothelial-derived cardioactive substances depends on the oxygen tension in the immediate vicinity of the cardiac myocytes. As the local oxygen tension increases the contractility changes in the same direction. The oxygen sensor in this regulatory system is the cardiac myocyte, which then releases substances that regulate the secretion of endothelin and a relaxant by endothelial cells. The result is a loop involving cross talk between coronary endothelial cells and cardiac myocytes to modulate cardiac contractility in accordance with the oxygen supply to the cardiac myocytes. Preliminary data suggest that the change in contractility is related to a change in structure and position of the cross bridge due to phosphorylation of a protein in the thick filament.


Esophagogastric junction adenocarcinomas: individualization of resection with special considerations for Siewert type II, and Nishi types EG, E=G and GE cancers.
For Siewert type II adenocarcinoma of the esophagogastric junction (AEG II), or similar tumors classified as Nishi EG, E=G, GE, the type of surgical resection and reconstruction should be individualized. Criteria for decision making mainly focus on the oral extent of esophageal infiltration, the cT and cN category and the functional status of the patient. For cT1/cT2 adenocarcinomas, which are non-poorly cohesive, intestinal type of Lauren Grading 1 or 2 without clinical signs of lymph node metastasis at the distal stomach, a limited transhiatal proximal gastrectomy with double tract reconstruction is recommended. For advanced adenocarcinomas, subtotal esophageal and proximal gastric resection with gastric pull-up or distal esophageal resection with total gastrectomy and esophagojejunostomy are competing procedures. Criteria for choosing the appropriate type of surgery are discussed.


Tyramine and benzylamine partially but selectively mimic insulin action on adipose differentiation in 3T3-L1 cells.
Biogenic amines like tyramine, methylamine and the non-naturally occuring amine, benzylamine, have been described to promote adipose conversion of murine 3T3 preadipocytes. To further investigate these novel effects of amines, we studied whether they selectively mimic the long-term adipogenic action of insulin. To this aim, we decided to use the 3T3-L1 cell line since this model needs a complex combination of inducers to trigger the differentiation programme: insulin, isobutylmethylxanthine (IBMX, an activator of cAMP-signal transduction pathway) and the synthetic glucocorticoid, dexamethasone. A cell culture protocol was designed, by which each component of the differentiation cocktail was replaced with either benzylamine or tyramine, in order to determine whether these amine oxidase substrates could substitute any of the differentiation inducers in 3T3-L1 cells. The incomplete lipid accumulation found in cells grown under IBMX- or dexamethasone-free conditions was not improved by the daily addition of amines to the culture medium. Insulin was the only component of adipose differentiation cocktail of 3T3-L1 that could be replaced, although partially, by tyramine or benzylamine. When used at 0.5 mM, these amines resulted in a significant increase of triacylglycerol accumulated eight days after confluence, when compared to cells kept without insulin. This partial insulin replacement was totally abolished by SSAO-inhibitors, while MAO-blockade did not reduce lipid accumulation. As previously reported for other insulin-sensitive processes, such as stimulation of glucose transport or lipolysis inhibition in mature adipocytes, the stimulation of adipogenesis by tyramine and benzylamine was an SSAO-dependent mechanism that apparently shared common signaling pathways with insulin.


Cavo-pulmonary shunt for left ventricular outflow tract obstruction after senning.
We report a case of Senning procedure in a 32-month-old girl with transposition of the great arteries and dynamic left ventricular outflow tract obstruction (LVOTO). After discontinuation of cardio-pulmonary bypass, the persisting, worsened LVOTO caused hemodynamical instability. A cavo-pulmonary shunt (CPS) was performed, with considerable subsequent improvement. We consider the use of CPS as a valuable option in patients with persisting, significant dynamic LVOTO after atrial switch.


Primary parotid carcinoma: analysis of risk factors and validation of a prognostic index.
Primary cancer of the parotid gland (PG) is a rare disease characterized by a wide variety of histologies and subtypes. The aim of the study was to identify factors influencing survival and validate the prognostic scores (PS1 and PS2) by Vander Poorten et al. STUDY DESIGN: Retrospective cohort study. All patients with previously untreated PG epithelial malignancies who underwent surgery with curative intent from 2002 to 2015 at a single center were retrospectively reviewed. 104 patients were included. Mean age was 60.2 years (range 14-88). Definitive pT staging was: 26 (25%) pT1, 19 (18.3%) pT2, 15 (14.4%) pT3, 41 (39.4%) pT4a, and 3 (2.9%) pT4b. Lateral neck nodal metastases were diagnosed in 27 (26%) patients. Five- and 10-year overall survival was 74.7% and 69.4%, respectively. Disease-specific survival at 5 and 10 years was 80.4% and 76.5%, respectively. Recurrence-free survival at 5 and 10 years was 66.9%. PS-1 and PS-2 scores correlated with prognosis. The most critical prognostic variables were grading, nodal metastases, perineural infiltration, lympho-vascular invasion, and skin infiltration. Major risk factors in primary PG carcinomas can effectively identify high-risk patients. The prognostic score by Vander Poorten et al. is a highly reliable tool to predict the prognostic profile.


Antidepressant drugs as emerging contaminants: Occurrence in urban and non-urban waters and analytical methods for their detection.
Antidepressants are drugs with a direct action on the brain's biochemistry through their interaction with the neurotransmitters, such as dopamine, norepinephrine, and serotonin. The increasing worldwide contamination from these drugs may be witnessed through their increasing presence in the urban water cycle. Furthermore, their occurrence has been detected in non-urban water, such as rivers and oceans. Some endemic aquatic animals, such as certain fish and mollusks, have bioaccumulated different antidepressant drugs in their tissues. This problem will increase in the years to come because the present COVID-19 pandemic has increased the general worldwide occurrence of depression and anxiety, triggering the consumption of antidepressants and, consequently, their presence in the environment. This work provides information on the occurrence of the most administrated antidepressants in urban waters, wastewater treatment plants, rivers, and oceans. Furthermore, it provides an overview of the analytical approaches currently used to detect each antidepressant presented. Finally, the ecotoxicological effect of antidepressants on several in vivo models are listed. Considering the information provided in this review, there is an urgent need to test the presence of antidepressant members of the MAOI and TCA groups. Furthermore, incorporating new degradation/immobilization technologies in WWTPs will be useful to stop the increasing occurrence of these drugs in the environment.


A clinical review of the adult hip guidance orthosis (Para Walker) in traumatic paraplegics.
Twenty Adult traumatic paraplegics with neurologically complete lesions between C8 and T12 have ambulated using a ParaWalker (adult hip guidance orthosis), for a minimum of 6 months at home. At follow up, on average 20 months from the date of issue of the orthosis, 17 patients (85%) were still regularly using their ParaWalker. Patients achieved independent use of the orthosis and low energy ambulation both indoors and outdoors on a variety of surfaces. A new classification of adult paraplegic ambulation using an orthosis is described.


Discovery of 1,2,4-triazole derivatives as novel neuroprotectants against cerebral ischemic injury by activating antioxidant response element.
Acute ischemic stroke is an important cause of death and long-term disability worldwide. In this work, we have synthesized a series of derivatives with 3,5‑diaryl substituent triazole scaffolds. The derivatives showed favorable protective effective in SNP-induced oxidative stress model, of which compound 5 was the most active. In vivo experiments showed that compound 5 could ameliorate neurological deficits, attenuate infarction sizes, reduce malonaldehyde (MDA) level and increase superoxide dismutase (SOD) level in middle cerebral artery occlusion (MCAO) rats. Preliminary safety evaluation showed that compound 5 exhibited low acute toxicity in BALB/c mice (LD50 greater than 1000 mg/kg). Further investigation indicated that compound 5 was able to scavenge ROS, restore mitochondrial membrane potential and protect PC12 cells from SNP-induced apoptosis. Moreover, compound 5 could initiate transcription of antioxidant response element (ARE) and induced expressions of antioxidative enzymes. Collectively, compound 5 might have the potency of treating acute ischemic stroke.


Multifid Iliopsoas Tendons Are More Common in Patients With Painful Snapping Iliopsoas Tendons.
To retrospectively determine the prevalence of multifid tendons in a population of patients who underwent iliopsoas release for painful snapping iliopsoas tendons. Patients who underwent iliopsoas release for painful snapping iliopsoas tendons were retrospectively identified from a database of patients who had undergone arthroscopic hip surgery performed by a single surgeon between 2011 and 2020. Patients who had incomplete data or who underwent prior fracture fixation, joint arthroplasty, pelvic surgery, or other interventions for snapping hip were excluded. Magnetic resonance imaging (MRI) and operative reports were reviewed and compared with those of an age-matched control group of patients who had undergone hip or pelvic MRI examinations in the past year for different indications. This study included 91 patients (78 female and 13 male patients; mean age, 23.3 years) who were treated operatively for painful snapping hip and 78 controls (54 female and 24 male patients; mean age, 28.4 years) who received hip or pelvic MRI for other indications. Among the patients who underwent iliopsoas release, there were 5 unifid iliopsoas tendons (5.5%) compared with 86 multifid iliopsoas tendons (94.5%) when classified with MRI whereas operative examination showed 19 unifid tendons (20.9%) compared with 72 multifid tendons (79.1%, P < .001). When the MRI scans of the operative group were compared with the MRI scans of the control group, the patients who underwent surgery for painful snapping hip had a higher rate of multifid tendons (94.5% of operative hips compared with 69.2% of control right hips [P < .001] and 74.4% of control left hips [P < .001]). However, when the operative reports were used to classify the iliopsoas tendon, there was no significance between the operative and control groups (79.1% of operative hips had multifid tendons compared with 69.2% of control right hips [P = .141] and 74.4% of control left hips [P = .464]). For patients with symptomatic snapping hip undergoing iliopsoas lengthening, multifid iliopsoas tendons are more prevalent than in a control population. Level IV, prognostic case series.


The outcome of childhood Haemophilus influenzae meningitis. A population based study.
To determine the morbidity and mortality from childhood Haemophilus influenzae type b (Hib) meningitis in a well defined population. Retrospective survey 1985-1987 and prospective surveillance of hospital laboratories 1989-1990. Information on outcome of meningitis was obtained from hospital records and attending physicians and, in 1989-1990, from a survey of the children's parents. Sydney Statistical Division, which had a population of children aged 0-4 years of 229,165 in 1986 and 263,758 in 1990. Eligible children were aged from one month to four years and had clinical and microbiological evidence of Hib meningitis on standard criteria. There were 229 eligible children. Twelve were excluded (seven died and five had pre-existing neurological deficits). A neurological deficit was detected at the time of hospital discharge in 45 patients (21%) and persisted for 12 months or longer in 29 patients (13%). Follow-up information was available for 165 (96%) children who were normal at the time of hospital discharge and persistent deficits were recorded in 12 (7%) of these children. Forty-one children (19%) had readily recognisable neurological or hearing problems: nine (4%) had persistent severe neurological deficits and seven (3%) had severe hearing loss requiring hearing aids or a cochlear implant. Age had a significant influence on outcome. The youngest children were significantly more likely to be admitted to intensive care. Severe neurological deficits showed a significant negative trend with increasing age (P = 0.03). Severe unilateral or bilateral sensorineural loss (odds ratio [OR] 8.0, 95% confidence interval [CI] 1.5-81) and ataxia at discharge (OR 13.3, 95% CI 2.8-128) were noticeably more common in children over two years of age, with a significant positive trend (P < or = 0.001) with increasing age. Patients requiring intensive care were much more likely to have an adverse outcome, particularly if positive pressure ventilation was needed. These data provide population-based estimates of the minimum incidence of adverse outcomes from Hib meningitis in an urban community with good access to medical services. This is important in assessing the impact of Hib vaccination, as meningitis is responsible for most of the long-term morbidity from childhood invasive Hib disease. Determination of the relationship between morbidity and age is important for assessing alternative vaccine strategies.


Community pharmacy professionals' practice in responding to minor symptoms experienced by pregnant women in Ethiopia: results from sequential mixed methods.
In countries with limited access to healthcare services, community pharmacists' management of minor symptoms experienced by pregnant women could be beneficial in terms of alleviating the burden of other health professionals and cost of services. However, evidence is limited regarding the practice of community pharmacy professionals in responding to minor pregnancy-related symptoms more generally, particularly in Ethiopia. The aim of this study was to evaluate actual and self-reported practice of community pharmacists in the management of minor symptoms during pregnancy in Ethiopia. A sequential mixed method study using self-reported survey from 238 community pharmacists followed by 66 simulated client visits was conducted from March to July 2020 in six towns of the Amhara regional state in Ethiopia. Independent samples t-test and one-way Analysis of Variance was used to test the mean difference of practice score among subgroups of study participants. The self-reported survey showed that most community pharmacist would 'always' gather most symptom-related information particularly about 'duration of symptoms,' 'frequency of symptoms,' and 'gestational age' and provide medication-related information on 'how to use the medication' and 'duration of use.' The highest mean practice scores were observed in relation to information gathering about 'gestational age' and information provision on 'how to use the medication.' In contrast, the lowest mean practice scores were observed in relation to information gathering about 'weight of the woman' and information provision on 'dosage form.' However, the actual practice, as revealed by the simulated client visits, demonstrated that most community pharmacists would rarely gather symptom-related information nor provide medication-related information. In addition, dispensing of non-prescribed medications to pregnant women was also common. The extent of self-reported practice differed among subgroups of study participants. This study highlights extent of practice of community pharmacy professionals during the management of minor symptoms in pregnancy in Ethiopia. Discrepancies of results between self-reported and actual practices of community pharmacy professionals were observed. The inadequate actual practice of symptom-related information gathering and medication-related information provisions needs considerations of implementing interventions to minimize potential harms.


Contrasting resource allocation patterns in Sedum lanceolatum Torr.: Biomass versus energy estimates.
Biomass determinations and microbomb calorimetry were used to assess resource allocation in Sedum lanceolatum Torr. between 2,257 and 3,726 m above sea level in the Front Range of the Rocky Mountains, Colorado, USA. In general, energy values did not differ within a tissue among sites, but did differ among tissue types. Flowers and leaves had the greatest energy content per gram ashfree dry weight. Total kilojoules per plant were homogeneous along the elevational gradient.Allocation patterns based on kilojoules of energy and grams of biomass were not highly correlated, with the exception of the percent investment in sexual tissues. Allocations to sexual tissues based on dry weight and energy were negatively correlated, revealing opposing trends of sexual investment with the increase in elevation. Due to the greater biomass investment in high energy leaves and flowers by populations of Sedum lanceolatum at higher elevations, allocation to sexual reproduction based on calorimetric analysis increased from 18.3 to 38.3% along the 1,469 m change in elevation. Although biomass can represent energy allocation in some taxa, for those species that change morphologically or physiologically along an environmental gradient, these two methods may not reveal similar trends.


Protonation-induced stereoisomerism in nicotine: conformational studies using classical (AMBER) and ab initio (Car-Parrinello) molecular dynamics.
A variety of biologically active small molecules contain prochiral tertiary amines, which become chiral centers upon protonation. S-nicotine, the prototypical nicotinic acetylcholine receptor agonist, produces two diastereomers on protonation. Results, using both classical (AMBER) and ab initio (Car-Parrinello) molecular dynamical studies, illustrate the significant differences in conformational space explored by each diastereomer. As is expected, this phenomenon has an appreciable effect on nicotine's energy hypersurface and leads to differentiation in molecular shape and divergent sampling. Thus, protonation induced isomerism can produce dynamic effects that may influence the behavior of a molecule in its interaction with a target protein. We also examine differences in the conformational dynamics for each diastereomer as quantified by both molecular dynamics methods.


Intestinal atresia.
Forty-five patients with intestinal atresia, including 20 with duodenal, 21 with jejunoileal, and 3 with colonic obstruction, were encountered at the Yale-New Haven Hospital between 1970 and 1976. The overall survival rate in the 43 operated cases was 93 per cent. The major reasons for the excellent operative survival with this malformation include: (1) the care received in a regional neonatal center; (2) the early recognition and appropriate case selection, denying operation unless mandated in babies with duodenal atresia and trisomy 21; (3) primary repair using modern surgical techniques which minimize anastomotic complications and the "blind-loop" and "short gut syndrome"; and (4) the use of uncomplicated long-term total parenteral nutrition in approximately one-half of operated cases.


Sex-related differences in heart failure.
Heart failure (HF) is a complex syndrome that is generally defined as cardiac output not adequate to meet the circulatory demands of the body. HF is at the end of the continuum of cardiovascular disease and preceded by an initiating event such as myocardial infarction, untreated hypertension, idiopathic cause, congenital heart disease, or pulmonary hypertension. In recent years, research has revealed differences in various aspects of HF between men and women including risk factors, pathophysiology, clinical manifestations, and response to treatment. Therefore, the purpose of this review is to review these sex-related differences between men and women who live with HF.


Enterocytozoon bieneusi in donkeys from Xinjiang, China: prevalence, molecular characterization and the assessment of zoonotic risk.
Enterocytozoon bieneusi, a zoonotic pathogen, has the potential to infect both immunocompromised and immunocompetent humans. It is found in large number of animals; however, not much is known regarding its prevalence in equine animals, particularly donkeys. This is the first molecular epidemiological evaluation of E. bieneusi in 178 free-ranging donkeys from five countrysides; and 502 farmed donkeys from 18 farms in 12 cities of Xinjiang, China by Nested PCR. E. bieneusi was detected in 2.5% (17/680) donkeys, with 2.6% (13/502) in farmed and 2.2% (4/178) in free-ranging ones. Sequence analysis identified eight ITS genotypes, all belonging to zoonotic Groups 1 or 2, including six known genotypes: horse1 (n = 5), D (n = 3), NCD-2 (n = 3), BEB6 (n = 2), BEB4 (n = 1), and NIAI (n = 1); and two new genotypes: XJD1 (n = 1) and XJD2 (n = 1). This is the first report confirming the presence of E. bieneusi in donkeys in Xinjiang, China, and indicates the possibility of zoonotic transmission of this pathogenic parasite.


Mixed mesodermal tumour of the cervix uteri. Case report.
A 44-year-old African female with a mixed mesodermal tumour of the cervix is described and the literature briefly reviewed.


Ultrasonography as a primary diagnostic tool in patients with inflammatory disease and tumors of the small intestine and large bowel.
In 240 patients with predefined indications, the validity of ultrasound imaging as a primary diagnostic procedure was examined prospectively. Ultrasonography revealed normal intestinal findings in 150 patients and pathological lesions in 90 subjects. All patients underwent subsequent endoscopic, radiological, or surgical examination. In 7 patients with Crohn's disease and in 2 patients with radiation colitis, the ultrasound findings were false-negative. In the other 9 cases, ultrasonography suggested false-positive results. Ultrasonographic examination of the small intestine and large bowel had a very high overall validity, with a sensitivity of 90% and specificity of 94%.


Stress in black, low-income, single-parent families: normative and dysfunctional patterns.
Stressful life events and the effects of demographic and social network variables were explored in a study of 50 clinic-referred and 76 nonclinic, black, low-income, single-parent families. Dysfunctional families evidenced greater stress and social network characteristics were not significant mediators. The family's internal resources may be the most important buffer against stress.


Sterol-O acyltransferase 1 is inhibited by gga-miR-181a-5p and gga-miR-429-3p through the TGFβ pathway in endodermal epithelial cells of Japanese quail.
Nutrients are utilized and re-constructed by endodermal epithelial cells (EECs) of yolk sac membrane (YSM) in avian species during embryonic development. Sterol O-acyltransferase 1 (SOAT1) is the key enzyme to convert cholesterol to cholesteryl ester for delivery to growing embryos. During embryonic development, yolk absorption is concomitant with significant changes of SOAT1 mRNA concentration and enzyme activity in YSM. Presence of microRNAs (miRNAs) are observed in the embryonic liver and muscle during avian embryogenesis. However, the expression of miRNAs in YSM during embryogenesis and the involvement of miRNAs in lipid utilization are not known. Using a miRNA sequencing technique, we found several miRNA candidates and confirmed their expression patterns individually by real time PCR. MiRNA candidates were selected based on the expression pattern and their possible roles in inhibiting transforming growth factor beta receptor type 1 (TGFBR1) that would regulate the function of SOAT1. Similar to SOAT1 mRNA, the gga-miR-181a-5p expression was gradually elevated during embryonic development. However, the expression of gga-miR-429-3p in YSM was gradually decreased during embryonic development. The inhibitory effects of gga-miR-181a-5p or gga-miR-429-3p on the potential targets (SOAT1 and TGFBR1) were demonstrated by transient miRNA transfections in EECs. We also found that mutated TGFBR1 3'UTR prevented the direct pairings of gga-miR-181a-5p and gga-miR-429-3p. Treatment of TGFBR1 inhibitor, LY364947, further decreased SOAT1 transcription. Similar results were also observed by the miRNA transfection studies. The results showed the vital participations of gga-miR-181a-5p and gga-miR-429-3p in regulating TGFβ pathway, and affecting downstream SOAT1 expression and function in the YSM. This is indicative of possible regulation of avian yolk lipid utilization by changing YSM miRNA expressions.


An effective long-wavelength fluorescent sensor for Cu2+ based on dibenzylidenehydrazine-bridged biphenylacrylonitrile.
Although numerous fluorescence sensors for Cu2+ have been presented, a long-wavelength sensor in aqueous media has rarely been reported as expected due to practical application requirements. In this work, a novel AIE molecule (DHBB) containing two biphenylacrylonitrile units bridged by dibenzylidenehydrazine was prepared. It possessed the merits of long-wavelength emission, good emission in aqueous media, and multiple functional groups for binding Cu2+. It exhibited good sensing selectivity for Cu2+ among all kinds of tested metal ions. The detection limit was as low as 1.08 × 10-7 M. The sensing mechanism was clarified as 1:1 stoichiometric ratio based on the binding cooperation of O and N functional groups of DHBB. The selective sensing ability for Cu2+ remained stable at pH = 5-9 and was influenced little by other metal ions. The Cu2+ sensing ability of DHBB was applied in real samples with 96% recovery rate. The bio-imaging experiment of living cells suggested that DHBB possessed not only good bio-imaging performance but also sensing ability for Cu2+ in living environments. This work suggested the good application prospect of DHBB to sense Cu2+ in real samples and living environment.


Poland syndrome and breast tumor: a case report and review of the literature.
Poland syndrome is a rare congenital malformation. Hypoplasia of the sternocostal portion of the pectoralis major muscle is the most significant feature and is most frequently associated with homolateral breast hypoplasia. In this article, the authors present a case of bilateral phyllodes tumors in a 28-year-old woman with Poland syndrome and discuss (1) the relationship between the condition and breast cancer, (2) the modes of surveillance in patients with Poland syndrome, and (3) its impact on breast reconstruction.


Species delimitation in the cyanolichen genus Rostania.
In this study, we investigate species limits in the cyanobacterial lichen genus Rostania (Collemataceae, Peltigerales, Lecanoromycetes). Four molecular markers (mtSSU rDNA, β-tubulin, MCM7, RPB2) were sequenced and analysed with two coalescent-based species delimitation methods: the Generalized Mixed Yule Coalescent model (GMYC) and a Bayesian species delimitation method (BPP) using a multispecies coalescence model (MSC), the latter with or without an a priori defined guide tree. Species delimitation analyses indicate the presence of eight strongly supported candidate species. Conclusive correlation between morphological/ecological characters and genetic delimitation could be found for six of these. Of the two additional candidate species, one is represented by a single sterile specimen and the other currently lacks morphological or ecological supporting evidence. We conclude that Rostania includes a minimum of six species: R. ceranisca, R. multipunctata, R. occultata 1, R. occultata 2, R. occultata 3, and R. occultata 4,5,6. Three distinct Nostoc morphotypes occur in Rostania, and there is substantial correlation between these morphotypes and Rostania thallus morphology.


Pathologic effusions localized on the anterior pararenal space: an in vivo demonstration.
The retroperitoneum is divided into three spaces by four fascial planes. This case reports outlining of the anterior pararenal space with opaque medium in a patient who developed large abscess cavities secondary to hemorrhagic pancreatitis. The contour of the cavities, their cross-communication, and their effect on adjacent organs and landmarks are described .


SNiPER: a novel hypermethylation biomarker panel for liquid biopsy based early breast cancer detection.
Mammography is the gold standard for early breast cancer detection, but shows important limitations. Blood-based approaches on basis of cell-free DNA (cfDNA) provide minimally invasive screening tools to characterize epigenetic alterations of tumor suppressor genes and could serve as a liquid biopsy, complementing mammography. Potential biomarkers were identified from The Cancer Genome Atlas (TCGA), using HumanMethylation450-BeadChip data. Promoter methylation status was evaluated quantitatively by pyrosequencing in a serum test cohort (n = 103), a serum validation cohort (n = 368) and a plasma cohort (n = 125). SPAG6, NKX2-6 and PER1 were identified as novel biomarker candidates. ITIH5 was included on basis of our previous work. In the serum test cohort, a panel of SPAG6 and ITIH5 showed 63% sensitivity for DCIS and 51% sensitivity for early invasive tumor (pT1, pN0) detection at 80% specificity. The serum validation cohort revealed 50% sensitivity for DCIS detection on basis of NKX2-6 and ITIH5. Furthermore, an inverse correlation between methylation frequency and cfDNA concentration was uncovered. Therefore, markers were tested in a plasma cohort, achieving a 64% sensitivity for breast cancer detection using SPAG6, PER1 and ITIH5. Although liquid biopsy remains challenging, a combination of SPAG6, NKX2-6, ITIH5 and PER1 (SNiPER) provides a promising tool for blood-based breast cancer detection.


Screening cell mechanotype by parallel microfiltration.
Cell mechanical phenotype or 'mechanotype' is emerging as a valuable label-free biomarker. For example, marked changes in the viscoelastic characteristics of cells occur during malignant transformation and cancer progression. Here we describe a simple and scalable technique to measure cell mechanotype: this parallel microfiltration assay enables multiple samples to be simultaneously measured by driving cell suspensions through porous membranes. To validate the method, we compare the filtration of untransformed and HRas(V12)-transformed murine ovary cells and find significantly increased deformability of the transformed cells. Inducing epithelial-to-mesenchymal transition (EMT) in human ovarian cancer cells by overexpression of key transcription factors (Snail, Slug, Zeb1) or by acquiring drug resistance produces a similar increase in deformability. Mechanistically, we show that EMT-mediated changes in epithelial (loss of E-Cadherin) and mesenchymal markers (vimentin induction) correlate with altered mechanotype. Our results demonstrate a method to screen cell mechanotype that has potential for broader clinical application.


Odor cue determinants of urine marking in male rats (Rattus norvegicus).
This study examined the spatial distribution of urine marking by sexually inexperienced male rats under six odor conditions: minimum odor (baseline), conspecific male urine, conspecific female urine, an animal's own urine, male gerbil urine, and amyl acetate. The gerbil urine and amyl acetate conditions were included to test the theory that marking, rather than being elicited by and directed as a display to appropriate conspecifics, occurred to the introduction of any novel or disruptive odor. The subject's own urine was used to test the theory that the animal marked to maintain an optimum level of its own odor in the environment. The results showed that marking was directed predominantly at objects in the environment over which the animal could readily pass. All odor conditions except "own odor" sharply increased marking over baseline levels. Marking decreased with repeated exposure to particular stimuli. The results strongly supported the theory that urine marking, at least in sexually inexperienced male rats, is produced by novel odor stimuli introduced into a familiar environment.


Three-Year Effectiveness of Dimethyl Fumarate in Multiple Sclerosis: A Prospective Multicenter Real-World Study.
Dimethyl fumarate (DMF) has demonstrated efficacy in phase III studies. However, real-world data are still limited. The objective of this study was to describe the profile of patients who receive DMF and to assess the effectiveness of DMF regarding relapses, disability progression, magnetic resonance imaging activity, and NEDA (No Evidence Disease Activity)-3 status in a Spanish population in a real-world setting. We conducted a multicenter prospective study of patients who started DMF between 2014 and 2019 in Spain. Three subgroups were considered: naïve, switch to DMF because of inefficacy, and switch to DMF because of adverse effects. The effects of DMF on clinical and radiological measures were evaluated. Among 886 patients, 25.3% were naïve, 28.8% switched because of adverse effects, and 45.9% because of inefficacy. Median follow-up was 38.9 (interquartile range 22.6-41.8) months. Annualized relapse rates were 0.15, 0.10, and 0.10 at 12, 24, and 36 months respectively, and 77.7% of patients were relapse free at month 42. At 12, 24, and 42 months, 96.1%, 87.4%, and 79.7% of patients were progression free, respectively. The number of T1 gadolinium-enhancement (T1Gd+) lesions was 0.19, 0.14, and 0.18 at 12, 24, and 36 months. NEDA-3 status at month 42 was maintained by 49.8% of patients. Relapsing was associated with higher annualized relapse rates the year before (hazard ratio 1.34, p < 0.001) and to the inefficacy switch vs naïve group (hazard ratio 1.76, p = 0.003). A higher baseline Expanded Disability Status Scale score was associated with disability progression (hazard ratio 1.15, p = 0.003) and more T1Gd+ lesions (hazard ratio 1.07, p < 0.001) with radiological progression. A higher baseline Expanded Disability Status Scale score, a larger number of T1Gd+ lesions, and a switch because of inefficacy (vs adverse events) were all risk factors for losing NEDA-3 status. DMF was discontinued in 29.9% of patients, in 13.5% because of inefficacy. Our findings confirm the sustained effectiveness of DMF on the clinical and radiological activity of multiple sclerosis in a real-world setting, both in naïve patients and in those switching from other multiple sclerosis therapies.


Roles of β-Indole Acetic Acid (IAA) Producing Endophytic Bacteria on the Recovery of Plant Growth and Survival Ability of Sugarcane Infected White Leaf Disease (SWLD).
β-Indole acetic acid is produced in the rhizosphere by endophytic bacteria and promotes plant growth. Effects of bacterial IAA producers (BIPs) on plant growth and recovery of sugarcane seedlings infected with phytoplasma causing white leaf disease (SWLD) were examined. Fifty-five endophytic bacteria isolated from rice roots were collected from the Mekong River Delta, Vietnam. Seven isolates showed β-Indole acetic acid production in culture medium supplemented with tryptophan. Interestingly, two of them (BC17 and BTII2) produced the highest β-Indole acetic acid after 4 days of culture. Based on 16S rRNA sequences and phylogenetic analysis, the BC17 and BTII2 isolates were identified as Delftia lacustris and Rahnella aquatilis, respectively. Plant growth induced by the BC17 and BTII2 isolates showed statistically significant differences in height, root length and fresh weight of rice seedlings compared with non-treatment as the control. Treatment of two bacterial isolates in SWLD infected sugarcane plants also showed differences in height of sugarcane seedlings, while gradual symptoms of exposure decreased plant mortality compared to non-treatment as the control. BIPs were shown to be efficient biofertilizer inoculants that promoted plant growth and also ameliorated damage caused by phytoplasma-associated diseases at the sugarcane seedling stage.


A novel hemizygous SACS mutation identified by whole exome sequencing and SNP array analysis in a Chinese ARSACS patient.
The array of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) has expanded worldwide after the first description in the Charlevoix-Saguenay region of Québec. Here, we report a Chinese ARSACS patient presenting progressive peripheral neuropathy (CMTNS2=15) with horizontal gaze nystagmus and mild spastic gait. Genetic studies including whole exome sequencing (WES), Sanger sequencing and single nucleotide polymorphism (SNP) array analysis revealed a novel hemizygous nonsense mutation (c.11803C>T, p.Gln3935X) of SACS and a 1.33Mb deletion involved in SACS on chromosome 13q12.12 in the patient. Our findings highlight the necessity of SACS mutation screening in the gene panel of inherited peripheral neuropathies, and stress the need of testing copy number variation (CNV) in SACS mutation screening.


High-grade and hormone-treated prostate cancer express high levels of thymidylate synthase.
To evaluate the expression of thymidylate synthase and dihydropyrimidine dehydrogenase in prostate tissue. Tissue from 79 patients with localized prostate cancer was used. Thymidylate synthase and dihydropyrimidine dehydrogenase expression were determined semiquantitatively by immunohistochemistry. Thymidylate synthase and dihydropyrimidine dehydrogenase immunostaining grades of benign tissue were significantly higher than those of cancer tissue (both P < 0.01). Cancer tissue with a primary Gleason grade of > or = 4 expressed a higher thymidylate synthase staining grade than those with a primary Gleason grade of <4 (P < 0.01). Cancer tissue spots from patients treated with neoadjuvant therapy revealed significantly higher thymidylate synthase and dihydropyrimidine dehydrogenase grades than those with no neoadjuvant therapy (P < 0.01). High thymidylate synthase expression in localized prostate cancer might reflect an aggressive status. High expression in high-grade prostate cancers and prostate cancers after hormonal therapy suggest that thymidylate synthase could be a new therapeutic target for advanced prostate cancer.


Bracing is an effective therapy for pectus carinatum: interim results.
Pectus Carinatum is a common congenital chest wall malformation. Until recently the mainstay of treatment was surgical remodeling of the deformed chest wall. Initial results suggest that non-operative bracing may be an effective therapy, but the optimal strategy for correction is not known. Herein we report the results of a self-adjustable low profile bracing system worn continuously until the defect is corrected (correction phase), then worn at night (8 h/day) until completion of axial growth (maintenance phase)-the Calgary Protocol. Patients referred to a pediatric surgery chest wall clinic were prospectively asked to join an IRB approved outcomes monitoring study. 124 patients were evaluated from 2007 to 2011, and 98 were prescribed a brace and counseled to follow the protocol. 98 patients consented to follow-up at starting bracing age: 14.4 ± 1.9 years, Tanner stage: 3.6 ± 0.5, protrusion: 2.1 ± 1.0 cm, self-rating of appearance: 2.9 ± 1.1, and exercise tolerance: 4.4 ± 1.1 (1-5 with 5 = normal). 10 patients are in correction phase, and 44 patients have completed correction after 7.0 ± 7.3 months: Tanner stage: 3.8 ± 0.1, protrusion: 0.5 ± 0.6 cm*, appearance: 4.3 ± 0.3* and exercise tolerance 4.6 ± 1.0. Correction occurred more quickly in patients prior to achieving Tanner stage IV (4.2 ± 0.9 months) vs. Tanner stage IV (8.0 ± 7.1 months) at the beginning of bracing. 21 patients completed maintenance bracing after 17.9 ± 19.0 months: Tanner stage: 3.9 ± 0.2, protrusion 0.5 ± 0.7 cm*, appearance: 4.3 ± 0.9*, and exercise tolerance: 4.8 ± 1.4. Average follow-up after bracing is 13.9 ± 16.0 months (mean ± S.D., *P < .05). There was one recurrence, likely due to early discontinuation of maintenance. This responded to an additional 6 months of bracing. 42 patients failed therapy secondary to non-compliance or were lost in follow up, while 2 patients did not respond to bracing and required open operation. If patients are compliant, a self- adjusting brace system can give rapid correction of the pectus carinatum protrusion with excellent patient satisfaction. These interim results suggest that continued bracing until skeletal maturity gives long term durability to the correction. Further studies will be required to further refine this promising therapy.


Prenatal Identification of Restrictive and Non-restrictive Ventricular Septal Defects Based on End-Systolic Flow Patterns in the Fetal Aortic Isthmus.
Fetuses with large ventricular septal defects (VSDs) must be closely monitored during the perinatal period. Intrauterine assessment of size of septal defects with bidimensional echocardiography are unreliable. The objective of the present study is to document the contribution of flow pattern analysis in the fetal aortic isthmus for prenatal identification of large non-restrictive VSDs requiring immediate postnatal attention. We conducted a cross-sectional retrospective study of Doppler recordings from patients referred to our Fetal Cardiology Unit and diagnosed with one or multiple VSDs from January 2006 to November 2015. Three groups were defined: (1) large non-restrictive VSDs (n = 11) with postnatal cardiac failure (2) small restrictive VSDs (n = 28) asymptomatic, and (3) absence of cardiac abnormality (n = 66). The Isthmic end-Systolic Index (ISI) was computed to quantify aortic isthmus flow and compared between the three groups. Fetuses with restrictive VSD and control group showed similar ISI: stable at 0.20 ± 0.01 up to 27 weeks of gestation and dropping later due to the fall of end-systolic velocities in the aortic isthmus. By 35 weeks, a brief end-systolic retrograde flow was present, associated with a further fall of ISI down to -0.26 ± 0.05. In contrast, ISI of fetuses with large non-restrictive VSDs were unchanged throughout gestation (0.18 ± 0.06), becoming significantly higher during the last weeks of gestation compared to the two other groups (p < 0.001). In fetuses with VSDs, the ISI measurement from the aortic isthmus Doppler flow during the second half of gestation is a reliable predictor of a large non-restrictive defect with risk of major postnatal clinical impact.


Ureteric lesions detected in normally functioning kidney allografts: risk factors and clinical implications.
We characterized the alterations in ureteral biopsies from normally functioning kidney allografts to study risk factors. We studied 55 ureteral fragments from kidney grafts obtained during cystoscopy for routine double-J stent extraction. We evaluated the type and severity of the lesions, the risk factors for their occurrence, and their relation to the evolution of the transplant, including the occurrence of renal rejection episodes or ureteral complications. Borderline or rejection lesions were detected in 21 of the 55 fragments. Rejection lesions were more common among biopsies performed in the first 80 days (54.6%) than during the 120 days afterward (15.4%, P = .043). Similarly, urothelium reactivity was detected in 71.4% and 30.7% of the biopsies performed up to and after 4 months, respectively (P = .008). Urothelial atrophy was detected in 20% of the fragments, the age of the donors being higher in these cases (P = .026). There was a trend to the association of borderline or rejection lesions in the ureteral biopsies and a history of an acute renal rejection episode (P = .053). There were no detectable relations between those findings and the evolution of the transplant. Thirty-eight percent of the biopsed ureters showed rejection or borderline lesions, these lesions were more common among biopsies done in the first months after transplantation. These findings are similar to the ones found in routine renal biopsies. We did not find any significant relation between the nature of the lesions encountered on the ureteral biopsies and the evolution of the transplant.


Role of computed tomography in the diagnosis of rib and lung involvement in tuberculous retromammary abscesses.
To assess the role of computed tomography (CT) in the diagnosis of rib and lung involvement in tuberculous abscess in the retromammary region. Eight patients with tuberculous retromammary abscess were examined by CT and the findings were evaluated. A cold abscess (purulent collection with absence of acute inflammation) was aspirated in all cases. Diagnosis was confirmed by acid-fast bacillus culture, or histologic examination. CT showed a relatively well marginated, inhomogeneous, hypodense lesions in all eight cases. Following administration of intravenous contrast medium, these lesions showed enhancing walls, suggestive of an infective collection. Lung involvement was seen in one patient. A direct communication from the retromammary lesion through the thoracic wall into the pleura was seen in five cases. In four cases destroyed rib fragments within the abscess were noted. A tuberculous abscess in the retromammary region is usually shown on CT as a focal, well-marginated, inhomogeneous, hypodense lesion with a surrounding enhancing rim. A direct communication with the pleura, a destroyed rib fragment in the abscess, and associated lung involvement may be revealed by CT.


Changes in electroencephalogram and heart rate during treadmill exercise in the rat.
To explore whether exercise is related to electroencephalogram (EEG) and heart rate changes, continuous EEG power spectral analysis was performed on rats during treadmill exercise. Compared with before exercise, treadmill exercise resulted promptly in a higher mean power frequency and theta (6-10 Hz) power of the EEG, but lower delta (0.5-4 Hz) power of the EEG together with a lower R-R interval of electrocardiogram. Such changes quickly reversed when the treadmill exercise was stopped. We conclude that the cerebral cortex activates along with the autonomic system during running. Our methodology offers an efficient way to study the interaction of cerebral and brain stem functions with exercise in the rat.


Prader-Willi syndrome with a karyotype 47,XY,+min(15)(pter->q11.1:) and maternal UPD 15--case report plus review of similar cases.
Prader-Willi (PWS) and Angelman (AS) are syndromes of developmental impairment that can result either from a 15q11-q13 deletion, paternal uniparental disomy (UPD), imprinting, or UBE3A mutations. A small cytogenetic subset of PWS and AS patients are carriers of a so-called small supernumerary marker chromosome (sSMC). Here, we report on an previously unreported PWS case with a karyotype 47,XY,+min(15)(pter->q11.1:) plus maternal heterodisomic UPD 15. A review of the literature revealed, that for both, PWS and AS patients, cases with (1) a sSMC plus microdeletion of the PWS/AS critical region, (2) inv dup(15) plus uniparental disomy (UPD) 15 and (3) cases without exclusion of a microdeletion an UBE3A mutation or UPD are described. The present case as well as the review of similar cases provides further evidence for the necessity to test UPD in prenatal cases with a de novo sSMC and in postnatal cases with otherwise unexplainable clinical phenotype.


A curated diverse molecular database of blood-brain barrier permeability with chemical descriptors.
The highly-selective blood-brain barrier (BBB) prevents neurotoxic substances in blood from crossing into the extracellular fluid of the central nervous system (CNS). As such, the BBB has a close relationship with CNS disease development and treatment, so predicting whether a substance crosses the BBB is a key task in lead discovery for CNS drugs. Machine learning (ML) is a promising strategy for predicting the BBB permeability, but existing studies have been limited by small datasets with limited chemical diversity. To mitigate this issue, we present a large benchmark dataset, B3DB, complied from 50 published resources and categorized based on experimental uncertainty. A subset of the molecules in B3DB has numerical log BB values (1058 compounds), while the whole dataset has categorical (BBB+ or BBB-) BBB permeability labels (7807). The dataset is freely available at https://github.com/theochem/B3DB and https://doi.org/10.6084/m9.figshare.15634230.v3 (version 3). We also provide some physicochemical properties of the molecules. By analyzing these properties, we can demonstrate some physiochemical similarities and differences between BBB+ and BBB- compounds.


Caspase-12 modulates NOD signaling and regulates antimicrobial peptide production and mucosal immunity.
Bacterial sensing by intracellular Nod proteins and other Nod-like receptors (NLRs) activates signaling pathways that mediate inflammation and pathogen clearance. Nod1 and Nod2 associate with the kinase Rip2 to stimulate NF-kappaB signaling. Other cytosolic NLRs assemble caspase-1-activating multiprotein complexes termed inflammasomes. Caspase-12 modulates the caspase-1 inflammasome, but unlike other NLRs, Nod1 and Nod2 have not been linked to caspases, and mechanisms regulating the Nod-Rip2 complex are less clear. We report that caspase-12 dampens mucosal immunity to bacterial infection independent of its effects on caspase-1. Caspase-12 deficiency enhances production of antimicrobial peptides, cytokines, and chemokines to entric pathogens, an effect dependent on bacterial type III secretion and the Nod pathway. Mechanistically, caspase-12 binds to Rip2, displacing Traf6 from the signaling complex, inhibiting its ubiquitin ligase activity, and blunting NF-kappaB activation. Nod activation and resulting antimicrobial peptide production constitute an early innate defense mechanism, and caspase-12 inhibits this mucosal antimicrobial response.


Stability of risk-adjusted primary cesarean delivery rates over time.
The purpose of this study was to compare how hospital rankings, based on risk-adjusted primary cesarean rates, change over time. Washington State Birth Events records data from 1995 through 1998 were used. Risk-adjustment models were built for each year. Risk-adjusted hospital rankings and outlier status (either "above" or "below" expected cesarean delivery rates) were calculated for each year. Hospitals that were identified as outliers for each year were compared with the use of kappa statistics. The top and bottom 25% of the hospital rank list from each year were also compared. The overall kappa statistic that compared outlier status over the 4 years was 0.44. The kappa statistic for the upper 25% of rankings over the 4 years was 0.42. The kappa statistic for the lowest 25% of rankings over the 4 years was 0.57. Although exact ranking may not be meaningful, outlier status, especially if repeated in multiple years may be a good marker for the identification of hospitals for further scrutiny of their quality of care.


Protracted postnatal natural histories in childhood leukemia.
Studies of monozygotic twins with concordant leukemia and scrutiny of archived neonatal blood by polymerase chain reaction (PCR) indicated that many pediatric leukemias are initiated prenatally by chromosomal translocation followed by a variable postnatal period before diagnosis of disease. The latter is thought to reflect a persistent preleukemic stage and a requirement for secondary genetic events. We sought to examine this further by examination of blood spots in rare cases of MLL fusion-positive or ETV6/RUNX1 (TEL-AML1) fusion gene-positive acute leukemia that were diagnosed at ages beyond the normal age range. We present evidence that the duration of the postnatal preleukemic state can occasionally be very protracted in these biological subtypes of pediatric leukemia, and we discuss its biological significance.


Phenotypes of food hypersensitivity and development of allergic diseases during the first 8 years of life.
Longitudinal data from population-based studies on the development and persistence of food hypersensitivity (FHS) during childhood are almost absent. A population-based birth cohort was established, and information on various exposures and symptoms of allergic disease were obtained from questionnaires when the children were 2 months, 1, 2, 4 and 8 years of age. Complete data were available on 3104 children. Children with reported FHS and doctor's diagnosis of food allergy (RDFA) were identified and allocated into transient, intermittent, late-onset and persistent phenotypes. Food allergen-specific IgE-antibodies (abs) to a mix of six common food allergens (fx5) were analysed at 4 and 8 years of age in 1857 children. The overall prevalence of reported FHS in combination with RDFA should be 3.1% at 1 year to 7.6% at 8 years of age. However, reactions to milk, egg, fish and wheat decreased, whereas an increase was seen for peanuts and tree nuts. Reported reactions to egg, peanuts or tree nuts early in life, as well as IgE-abs to food allergens at the age of 4, increased the risk of FHS at 8 years of age. Furthermore, FHS at young ages increased the risk for asthma, eczema and allergic rhinitis at 8 years of age, even when adjustments were made for children with these symptoms during the first 2 years of life. The increasing prevalence of FHS up to the age of 8 years probably reflects an increasing prevalence of allergy to birch pollen and pollen-related reactions to foods. Reactions to egg, peanuts and tree nuts early in life increase the risk of FHS at 8 years. Furthermore, reported FHS at young ages, even though transient, seems to increase the risk for other allergic diseases at 8 years of age.