Cyclin E deregulation alters the biologic properties of ovarian cancer cells.
We have previously shown that the low molecular weight (LMW) forms (trunk 1 and trunk 2) of cyclin E are biochemically hyperactive and induce G1/S progression in normal epithelial cells. Here we investigate the biologic consequences of LMW cyclin E expression in ovarian cancer cells. Using a panel of ovarian carcinoma tumors we find that cyclin E overexpression is invariably due to the presence of LMW forms and that expression of these forms appears to correlate with more advanced grade and stage of disease. Despite similar expression of p21 and p27, cyclin E overexpressing tumors have higher kinase function. Using an isogenic ovarian cancer model, we find that clones that overexpress the trunk 1 (T1) protein have a 10-fold increase in cyclin E kinase function, a 20% increase in S-phase fraction, a 10-15% decrease in doubling time and a 20% increase in colony formation compared to parental cells that express only the FL cyclin E protein. T1 clones were resistant to G1 arrest but more sensitive to cisplatin. Therefore, in ovarian tumors, the presence of LMW cyclin E forms confers altered biologic properties. Our data provides a potential mechanism for the poor prognosis of patients with LMW cyclin E expressing tumors.


Savings in classical conditioning in the rabbit as a function of extended extinction.
In the present experiments, savings phenomena following a limited amount of initial acquisition and extended extinction were examined. Experiments 1 and 2 compared rates of reacquisition following brief acquisition and various amounts of extinction in conditioning of the rabbit's nictitating membrane and heart rate response, respectively. Experiment 3 compared rates of acquisition to a novel stimulus (e.g., light) following brief acquisition and various amounts of extinction to another stimulus (e.g., tone). In addition, in Experiment 3 recovery of responding to the extinguished stimulus during acquisition to the novel, cross-modal stimulus was examined. Experiments 1, 2, and 3 demonstrated that with a limited number of acquisition trials (1) there was a graded reduction in the rate of reacquisition as a function of the number of extinction trials in both conditioning preparations, (2) there was a graded reduction in the rate of cross-modal acquisition as a function of the number of extinction trials, but (3), in Experiment 3, recovery of responding to the extinguished stimulus during cross-modal training of the novel stimulus appeared uniformly robust even in the face of extended extinction.


Implantable arterial port-related bloodstream infection in patients with primary or metastatic hepatic malignancies.
The incidence of implantable arterial post-related bloodstream infections (IAP-RBSI) among patients with unresectable hepatic malignancies is not well defined. We reviewed the 9-year incidence of implantable arterial post-related bloodstream infections in patients with hepatic malignancies, at a tertiary care center in Japan. The incidence was 1.9 infections per 10,000 catheter-days.


Endogenous Nocardial Endophthalmitis Misdiagnosed as Giant Cell Arteritis.
Endogenous endophthalmitis is uncommon but potentially dangerous. We present a fatal presentation of endogenous Nocardial endophthalmitis in the context of steroid use for treatment of giant cell arteritis. An 84-year-old Caucasian female presented to the local emergency room with severe headaches, myalgia and shoulder and calf muscle pain. She was treated for a presumed diagnosis of giant-cell arteritis with corticosteroids and subsequently developed an intense retro-orbital pain in the right eye. Fundus examination revealed a white, vascularized chorioretinal mass at the equator of the eye in the inferotemporal quadrant. Antibiotics were given and a vitrectomy was performed. The culture of the vitreous showed Nocardia nova and a diagnosis of disseminated Nocardiosis was made. Although uncommon, it is important that ophthalmologists are aware of Nocardial infections as a differential diagnosis of retinal mass, particularly in immunocompromised patients.


Stress, memory, and emotion: developmental considerations from the study of child maltreatment.
Emotion and memory are examined within a developmental framework. The point of departure for this discussion is the study of maltreated children whose traumatic experiences have been linked to difficulties in emotional development. It is suggested that cognitive processes such as memory and attention serve to link experience with emotion and emotion with psychopathology. Thus, an information processing approach is used to explain the development of maltreated children's adaptive and maladaptive coping responses. It is argued that maltreated children's association of affective stimuli with traumatic experiences and memories selectively alters the meaning of emotions for these children. More generally, the role of experience and learning as a component of emotional development is emphasized.


Defunctioning loop ileostomy in anterior resection for rectal cancer and subsequent renal failure: nationwide population-based study.
Electrolyte disturbances and dehydration are common after anterior resection for rectal cancer with a defunctioning loop ileostomy. High-quality population-based studies on the impact of a defunctioning loop ileostomy on renal failure are lacking. This was a nationwide observational study, based on the Swedish Colorectal Cancer Registry of patients undergoing anterior resection for rectal cancer between 2008 and 2016, with follow-up until 2017. Patients with severe co-morbidity, with age greater than 80 years, and with pre-existing renal failure were excluded. Loop ileostomy at index surgery constituted exposure, while a diagnosis of renal failure was the outcome. Acute and chronic events were analysed separately. Inverse probability weighting with adjustment for confounding derived from a causal diagram was employed. Hazards ratios (HRs) with 95 per cent c.i. are reported. A total of 5355 patients were eligible for analysis. At 5-year follow-up, all renal failure events (acute and chronic) were 7.2 per cent and 3.3 per cent in the defunctioning stoma and no stoma groups respectively. In the weighted analysis, a HR of 11.59 (95 per cent c.i. 5.68 to 23.65) for renal failure in ostomates was detected at 1 year, with the largest effect from acute renal failure (HR 24.04 (95 per cent c.i. 8.38 to 68.93)). Later follow-up demonstrated a similar pattern, but with smaller effect sizes. Patients having a loop ileostomy in combination with anterior resection for rectal cancer are more likely to have renal failure, especially early after surgery. Strategies are needed, such as careful fluid management protocols, and further research into alternative stoma types or reduction in stoma formation.


Sociodemographic Variables Reporting in Human Radiology Artificial Intelligence Research.
Artificial intelligence (AI) is rapidly reshaping how radiology is practiced. Its susceptibility to biases, however, is a primary concern as more AI algorithms become available for widespread use. So far, there has been limited evaluation of how sociodemographic variables are reported in radiology AI research. This study aims to evaluate the presence and extent of sociodemographic reporting in human subjects radiology AI original research. All human subjects original radiology AI articles published from January to December 2020 in the top six US radiology journals, as determined by impact factor, were reviewed. Reporting of any sociodemographic variables (age, gender, and race or ethnicity) as well as any sociodemographic-based results were extracted. Of the 160 included articles, 54% reported at least one sociodemographic variable, 53% reported age, 47% gender, and 4% race or ethnicity. Six percent reported any sociodemographic-based results. There was significant variation in reporting of at least one sociodemographic variable by journal, ranging from 33% to 100%. Reporting of sociodemographic variables in human subjects original radiology AI research remains poor, putting the results and subsequent algorithms at increased risk of biases.


Correcting high astigmatism with piggyback toric intraocular lens implantation.
An 86-year-old man presented for cataract surgery with corneal astigmatism of 5.12 diopters (D). After cataract extraction with small-incision techniques, 2 toric plate-haptic silicone intraocular lenses (IOLs) were implanted in the capsular bag, each with a 3.50 D cylinder add (2.30 D at the spectacle plane). Six weeks postoperatively, corneal astigmatism was 3.38 D at 70 degrees and refractive astigmatism was 1.00 D at 20 degrees. Uncorrected visual acuity was 20/40. No IOL rotation was observed. Implantation of piggybacked toric lenses may be a viable option for correcting moderate to high astigmatism.


Retracted: Optimization Research on Deep Learning and Temporal Segmentation Algorithm of Video Shot in Basketball Games.
[This retracts the article DOI: 10.1155/2021/4674140.].


The carboxyl-terminal ahnak domain induces actin bundling and stabilizes muscle contraction.
Ahnak, a 700 kDa protein, is expressed in a variety of cells and has been implicated in different cell-type-specific functions. In the human heart, we observed an endogenous carboxyl-terminal 72 kDa ahnak fragment that copurified with myofibrillar proteins. Immunocytochemistry combined with confocal microscopy localized this fragment to the intercalated discs and close to the Z-line of cardiomyocytes. No endogenous myofibrillar ahnak fragment was observed in the skeletal muscle. We elucidated the role of the recombinant carboxyl-terminal ahnak fragment (ahnak-C2) in actin filament organization and in the function of muscle fibers. Addition of ahnak-C2 to actin filaments induced filament bundling into paracrystalline-like structures as revealed by electron microscopy. Incubation of demembranated skeletal muscle fibers with ahnak-C2 attenuated the decline in isometric force development upon repeated contraction-relaxation cycles. Our results suggest that the carboxyl-terminal ahnak domain exerts a stabilizing effect on muscle contractility via its interaction with actin of thin filaments.


Proximal renal tubular dysfunction in severe burns.
Proximal renal tubular function was studied in 11 patients with severe burn injury. Creatinine clearance was normal or increased in ten patients. Fractional excretion of sodium was less than 1% in ten. Fractional excretion of uric acid and amylase were increased in all but four and two cases, respectively, while absolute clearances of lysozyme and beta 2-microglobulin were increased in all but one patient. Renal threshold phosphate concentration was reduced in four patients. Twenty-four-hour urine glucose excretion exceeded 1 g in five patients, aminoaciduria was noted in eight, and proteinuria, predominantly globulinuria, was present consistently. Metabolic acidosis was seen in one patient, and transient hypokalemia occurred in two. Abnormalities of proximal tubular function were more marked in the five patients with the greatest extent of third-degree burns who died. The cause of proximal tubular dysfunction is not clear and may be related to an adaptive response to severe injury.


A new approach to characterization of insulin derived from different species using 1H-NMR coupled with multivariate analysis.
Most of the active components of polypeptides have a complex molecular structure, large molecular size. Such components may also be structurally heterogeneous. Therefore, development of a method that can confirm the consistency of polypeptides amino-acid sequences for product characterization is desirable. In general, it is extremely difficult to distinguish differences of a few amino acid residues in the 1H-NMR spectrum of polypeptides with molecular weights greater than several thousand. However, we have been able to distinguish between three insulin species differing in one to three amino acid residues using a combination of multivariate statistics and 1H-NMR spectra. These results demonstrate that this methodology could be useful for characterization of polypeptides.


Endonuclease III: an endonuclease from Escherichia coli that introduces single polynucleotide chain scissions in ultraviolet-irradiated DNA.
An endonuclease that makes single polynucleotide chain scissions in UV-irradiated DNA has been purified from Escherichia coli. The activity has the following properties: (1) unirradiated DNA is attacked very little if at all; (2) single-stranded DNA is not attacked, whether irradiated or not; (3) there is no requirement for divalent cations, and the activity is not affected by addition of EDTA; (4) the pH optimum is approximately 7; (5) the activity is inhibited by 1 M NaCl, single-stranded DNA, transfer RNA, and unirradiated double-stranded DNA; (6) the sedimentation coefficient, S20, W, is approximately 2.6; (7) it is a basic protein. The enzyme is tentatively named E. coli endonuclease III. The physiological function of the endonuclease has not yet been established.


Computing Ligands Bound to Proteins Using MELD-Accelerated MD.
Predicting the poses of small-molecule ligands in protein binding sites is often done by virtual screening algorithms such as DOCK. In principle, molecular dynamics (MD) using atomistic force fields could give better free-energy-based pose selection, but MD is computationally expensive. Here, we ask if modeling employing limited data (MELD)-accelerated MD (MELD × MD) can pick out the best DOCK poses taken as input. We study 30 different ligand-protein pairs. MELD × MD finds native poses, based on best free energies, in 23 out of the 30 cases, 20 of which were previously known DOCK failures. We conclude that MELD × MD can add value for predicting accurate poses of small molecules bound to proteins.


Influence of different electrolytes and oils on the stability of W1/O/W2 double emulsion during storage and in vitro digestion.
The aim of this study is to formulate a stable water-in-oil-in-water (W1/O/W2) double emulsion using different types of oils and electrolytes. W1/O was formulated with different electrolyte solutions (W1) dispersed in various oils (O) using polyglycerol polyricinoleate as a stabilizer. External aqueous phase was Tween-80 (W2), and W1/O dispersed in W2 was used. The emulsion containing NaCl or MgCl2 exhibited high encapsulation efficiency (EE) and maintained particle size. Regarding the oil type, the emulsion with MCT oil showed a small droplet size and a high viscosity and EE, presenting a stable droplet distribution in optical observation. The stability of emulsion containing NaCl was maintained during the in vitro digestion experiments. MCT oil, NaCl and MgCl2 have the potential to produce stable double emulsions for storage stability and in vitro digestion studies. The findings would be useful for preparing stable double emulsions used in the food and cosmetic industries.


Quality assurance methodology and applications to abdominal imaging PQI.
Quality assurance has increasingly become an integral part of medicine, with tandem goals of increasing patient safety and procedural quality, improving efficiency, lowering cost, and ultimately improving patient outcomes. This article reviews quality assurance methodology, ranging from the PDSA cycle to the application of lean techniques, aimed at operational efficiency, to continually evaluate and revise the health care environment. Alignment of goals for practices, hospitals, and healthcare organizations is critical, requiring clear objectives, adequate resources, and transparent reporting. In addition, there is a significant role played by regulatory bodies and oversight organizations in determining external benchmarks of quality, practice, and individual certification and reimbursement. Finally, practical application of quality principles to practice improvement projects in abdominal imaging will be presented.


Therapeutic depletion of myeloid lineage leukocytes in patients with generalized pustular psoriasis indicates a major role for neutrophils in the immunopathogenesis of psoriasis.
Generalized pustular psoriasis (GPP) is a chronic autoimmune disease characterized by fever, erythema, and neutrophilic pustules over large areas of the skin. GPP does not respond well to pharmacologic intervention. We sought to assess efficacy of selectively depleting the myeloid lineage leukocytes in patients with GPP. Fifteen patients with persistent moderate to severe GPP despite conventional therapy were included. Eligible patients had more than 10% of their skin area covered by pustules. Treatment with oral etretinate, cyclosporine, methotrexate, prednisolone, and topical prednisolone/vitamin D3 was continued if had been initiated well in advance of study entry. Five sessions of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn (JIMRO Co Ltd, Takasaki, Japan) were administered (1 session/wk over 5 weeks) to selectively deplete Fcγ receptor and complement receptor bearing leukocytes. Efficacy was assessed by measuring the skin areas covered by pustules at baseline and 2 weeks after the last GMA session. One patient did not complete the first GMA session. Based on the GPP severity scores relative to entry, the overall scores improved (n = 14, P = .0027), and the area of erythroderma (P = .0042), pustules (P = .0031), and edema (P = .0014) decreased. Likewise, Dermatology Life Quality Index improved (P = .0016), reflecting better daily function and quality of life. Twelve patients were judged as responders (85.7%), and 10 patients maintained the clinical response for 10 weeks after the last GMA session without any change in medication. This study was unblinded and without a placebo arm. GMA in this clinical setting was safe and effective, suggested a major role for granulocytes/monocytes in the immunopathogenesis of GPP.


Discovery and optimization of a potent and selective indazolamine series of IRAK4 inhibitors.
IRAK4 is a key mediator of innate immunity. There is a high interest in identifying novel IRAK4 inhibitors for the treatment of inflammatory autoimmune diseases. We describe here a highly potent and selective IRAK4 inhibitor (HS271) that exhibited superior enzymatic and cellular activities, as well as excellent pharmacokinetic properties. HS271 displayed robust in vivo anti-inflammatory efficacy as evaluated in rat models of LPS induced TNFα production and collagen-induced arthritis.


Correlation of physical, psychological, and functional factors with independent medication adherence in Korean older adults with chronic illness: Using the 2017 national survey of older Koreans.
To identify the differences in sight, hearing, cognitive function, depression, and activities of daily living and the relationships between the research variables according to the independent medication adherence of Korean older adults with chronic illness. Data were taken from the 2017 National Survey of Older Koreans. The sample comprised 8333 household-dwelling participants aged 65 and older, who had one or more chronic diseases. Korean older adults were, on average, diagnosed with 3.21 chronic illnesses and taking 4.55 doctor-prescribed medications. There were significant differences in age, education level, living arrangement, perceived subjective health states, number of diagnosed chronic diseases, number of prescription medications being taken, level of discomfort with daily living due to decline in sight and hearing, cognitive function, depression, and levels of activities of daily living according to independent medication adherence. For Korean older adults with independent medication adherence, cognitive function had significant correlations with perceived subjective health states, depression, and daily living activities. For those with partially-dependent or dependent medication adherence, lower cognitive function was associated with greater discomfort due to hearing, and depression had significant correlations with perceived subjective health states, number of prescription medications being taken, and discomfort due to decline in sight and hearing, but significant correlation with level of cognitive function. Nursing intervention should be planned to enhance the medication adherence of Korean older adults. Specifically, cognitive function, depression, and activities of daily living must be considered along with the patient's health.


Potential effects of adverse childhood experiences on school engagement in youth: a dominance analysis.
Adverse childhood experiences (ACEs) can have severe negative impacts on childhood and adult health via worsened school engagement and educational outcomes. This study seeks to identify the relative importance of various ACEs in predicting school engagement. We analyzed data from the National Survey of Children's Health for school-aged children (ages 6-17) for 2018 and 2019. The primary outcome was school engagement, measured through three variables: repeating a grade, doing required homework, and caring about doing well in school. We conducted three logistic regression models with dominance analyses to identify the relative importance of ACE variables in predicting school engagement outcomes. In unadjusted and adjusted dominance analyses, parental incarceration was the most important ACE in predicting repeating a grade. Living in a household in which it was hard to cover basics like food or housing was the most important ACE in predicting doing required homework and caring about doing well in school. Our study points toward the large influence of out-of-school factors on school engagement. Parental incarceration and economic hardship, the most important predictors of engagement, are issues that can be addressed and mitigated through policy interventions. With limited funds available for education and public health interventions, it is crucial that these two ACEs be priority considerations when developing policy. A multi-faceted approach that reduces the incarcerated population, encourages economic well-being, and emphasizes early-childhood education has the potential to significantly improve school engagement in vulnerable populations and ultimately advance social equity.


Germacrone, A Novel and Safe Anticancer Agent from Genus Curcuma: A Review of its Mechanism.
Germacrone, a kind of natural sesquiterpenoid compound, has been reported to exhibit many pharmacological properties, especially the anticancer effect. Many in vitro experiments have been performed on various cancer cell lines, trying to explore their anticancer mechanism. Aiming at investigating the anticancer effect of germacrone, this article reviews the extant information on existing literature about germacrone-related studies. The anticancer mechanisms and clinical usages of germacrone are summarized. Literature databases (such as PubMed and CNKI) are used to search the current studies and experimental research about the anticancer effect information of germacrone. Anticancer mechanism of germacrone includes cell cycle arrest inducing, programmed cell death (apoptosis, autophagy, pyroptosis and ferroptosis) inducing, and estrogen-related genes mediating. Structural modification and analogue design are worthy of further study in the future.


Semi-automated liquid chromatography-mass spectrometric imaging platform for enhanced detection and improved data analysis of complex peptides.
A semi-automated analytical platform featuring the coupling of monolithic reversed-phase liquid chromatography (RPLC) to matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI MSI) has been developed and evaluated. This is the first time that LC separation is readily coupled to MS imaging detection for the analysis of complex peptide mixtures both qualitatively and quantitatively. Methacrylate-based monolithic column with C12 functional groups is fabricated for fast RPLC separation. The LC flow and matrix flow are collected on a commercially available MALDI plate which is mechanically controlled and analyzed with MALDI MSI subsequently. Both tryptic peptides digested from bovine serum albumin (BSA) and endogenous neuropeptides extracted from the blue crab Callinectes sapidus are analyzed with this novel LC-MSI platform. Compared with regular offline LC fractionation coupled with MALDI MS detection, LC-MSI exhibits significantly increased MS signal intensity due to retaining of temporal resolution from separation dimension via continuous sampling, which results in increased number of peptides detected and accurate quantitation. In addition, imaging signals enable improved data analysis based on either mass-to-charge ratio or retention time, which is extremely beneficial for the analysis of complex analytes. These findings have demonstrated the potential of employing LC-MSI platform for enhanced proteomics and peptidomics studies.


Comparison of Cardiac Output Measurement by Electrical Velocimetry with Echocardiography in Extremely Low Birth Weight Neonates.
Electrical velocimetry (EV) offers a noninvasive tool for continuous cardiac output (CO) measurements which might facilitate hemodynamic monitoring and targeted therapy in low birth neonates, in whom other methods of CO measurement are not practicably feasible. This prospective observational study compared simultaneous cardiac output measurements by electrical velocimetry (COEV) with transthoracic echocardiography (COTTE) in extremely low birth weight (ELBW) neonates in the neonatal intensive care unit (NICU). Echocardiography was performed by 1 single examiner. Data were analyzed by Bland-Altman analysis and independent-samples analysis of variance. A mean percentage error (MPE) of <30% and limits of agreement (LOA) up to ±30% were considered clinically acceptable. Thirty-eight ELBW neonates were studied and yielded 85 pairs of COEV and COTTE measurements. Bland-Altman analysis showed an overall bias (the mean difference) and LOA of -126 and -305 to +52 mL min-1, respectively, and an MPE of 66%. Patients with patent ductus arteriosus had a higher bias with LOA and MPE of -166.8, -370.7 to +37 mL min-1, and 69%, respectively. The overall true precision was 58%. This study showed high bias and lack of agreement between EV and TTE for measurement of CO in ELBW infants in NICU, limiting applicability of EV to monitor absolute values.


Exploring the type and strength of nonlinearity in water quality responses to nutrient loading reduction in shallow eutrophic water bodies: Insights from a large number of numerical simulations.
Reducing the load of nutrients is essential to improve water quality while water quality may not respond to the load reduction in a linear way. Despite nonlinear water quality responses being widely mentioned by studies, there is a lack of comprehensive assessment on the extent and type of nonlinear responses considering the seasonal changes. This study aimed to measure the strength of nonlinearity of theoretically possible water quality responses and explore their potential types in shallow eutrophic water bodies. Hereto, we generated 14,710 numerical water body cases that describe the water quality processes using the Environmental Fluid Dynamics Code (EFDC) and applied eight load reduction scenarios on each water body case. Inflows are simplified from Lake Dianchi. The climate conditions consider three cases: Lake Dianchi, Wissahickon Creek, and Famosa Slough. We then developed a nonlinearity strength indicator to quantify the strength and frequency of nonlinear water quality responses. Based on the quantification of nonlinearity, we clustered all the samples of water quality responses using K-Means, an unsupervised Machine Learning algorithm, to find the potential types of nonlinear water quality responses for TN (total nitrogen), TP (total phosphorus), and Chla (chlorophyll a). Results show linear or near-linear response types account for 90%, 69%, and 20% of TN, TP, and Chla samples respectively. TP and Chla could perform more types of nonlinearity. Representative nonlinear water quality responses include disproportional improvement, peak change (disappear, move forwards or afterward), and seasonal deterioration of TN after load reduction. This study would contribute to the current understanding of nonlinear water quality responses to load reduction and provide a basis to study under which conditions the nonlinear responses may emerge.


How to manage lower-risk myelodysplastic syndromes.
Patients with lower-risk myelodysplastic syndromes (MDSs), usually defined as having an International Prognostic Scoring System score of 1.0 or less, and/or <5% myeloblasts, comprise the majority of newly diagnosed and established MDS patients and have a survival measured in years. Most will eventually require therapy for their disease, usually when MDS-related symptoms or transfusion requirements accelerate and outweigh potential drug-related toxicities. The decision of when to initiate therapy is far from straightforward. Erythropoiesis stimulating agents yield responses in up to 40% of appropriately selected patients, while disease-modifying drugs, including lenalidomide, azacitidine, decitabine and anti-thymocyte globulin, can evoke responses as high as 67% in patient subgroups. Newer therapies hold the promise of activity in patients who have failed standard regimens.


Fibrinous membrane formation on the posterior chamber lens during the early postoperative period.
I observed transient membrane formation consisting primarily of fibrin on the anterior surface of the IOL in 45 (7.6%) of the 596 eyes that received posterior chamber lens implantation during the past year. The onset of the condition was generally five to six days after surgery. This membrane characteristically developed between the margins of the anterior capsule, and therefore might be the result of lens-induced uveitis from the proliferation of lens epithelial cells under the anterior capsule.


Basal cell epithelioma in a vaccination scar.
A 42-year-old woman developed a superficial basal cell epitheliol in a smallpox vaccination scar. After reviewing similar reports in the English literature, I believe any unusual change occurring in a vaccination scar, either simultaneously or years later, should be viewed as a possible malignancy and treated accordingly.


Parovarian cystadenoma: sonographic features associated with magnetic resonance and histopathologic findings.
Differentiation between malignant and benign parovarian tumors is necessary before any surgery is planned, because the postoperative spread of ovarian cancers is well documented. Both malignant and benign parovarian tumors may contain intracystic projections, so their presence is not a differentiating factor. We describe the cases of 2 patients with parovarian cystadenomas that were evaluated using sonography, MRI, and histopathology in an attempt to begin to identify the sonographic characteristics of such lesions and correlate them with MRI and histopathologic findings. In both cases, sonography revealed a cystic mass that contained multiple small intracystic mural nodules, most of which were associated with the "Chinese hat" artifact. MRI findings confirmed the presence of the cystic masses and the nodules. Histopathologic findings confirmed the diagnosis of serous cystadenoma arising in a parovarian cyst; the intracystic nodules consisted of fibrotic tissue covered with a single layer of epithelium. Thus, the results of all 3 evaluations correlated well. This characteristic sonographic appearance may be useful in making an accurate preoperative diagnosis of parovarian cystadenomas.


Clinical, endoscopic, histological and radiological characteristics of Italian patients with eosinophilic oesophagitis.
Limited data are available on eosinophilic oesophagitis in Italy. To evaluate typical features of eosinophilic oesophagitis patients in a tertiary centre. 973 consecutive patients with dysphagia and/or bolus impaction were prospectively enrolled and underwent upper endoscopy for eosinophilic oesophagitis (≥15 eosinophils in at least one high-power field [hpf] and no response to acid suppressants). Demographic and multiple clinical factors were collected. 45 patients (80% males, mean age 35±16) with incident eosinophilic oesophagitis (mean eosinophil peak count 57.2±40.6/hpf) were enrolled. 32 patients complained of solids dysphagia (71%), and 29 of bolus impaction (64%). Endoscopy found rings in 20 (44%), furrows in 9 (20%), whitish exudates/plaques in 12 (27%), crêpe paper in 7 (13%) and normal findings in 14 patients (31%). Endoscopic and radiologic stenosis occurred in 20 (44%) and 23 (51%), respectively. Ten patients had proton pump inhibitor-oesophageal eosinophilia (22%). Topic fluticasone was effective in 28 of the remaining cases (62%), while 7 required additional treatments (16%). Eosinophilic oesophagitis prevalence was 12% in patients with dysphagia and/or bolus impaction, emphasizing the importance of this disease in Italy. Despite different environmental factors and dietary habits, Italian patients with eosinophilic oesophagitis present similar characteristics to those of other Western counties.


Two-step irradiance schedule for condyloma acuminatum and the influencing factors of analgesic effect: A prospective randomized study.
The two-step irradiance schedule in photodynamic therapy (PDT) is an emerging treatment method with a remarkable analgesic effect. We evaluated the influencing factors of pain in condyloma acuminate (CA) treatment with a two-step irradiance schedule. All patients were randomly divided into a two-step irradiance group and control group. The two-step irradiance group used 40 mW/cm2 for the first 8min, followed by 80 mW/cm2 for 16 min, while the control group used 80 mW/cm2 for 20 min. The Numerical Rating Scale (NRS) scores and pain-influencing factors were recorded accordingly. In the two-step irradiance and control groups, 64 and 63 patients completed the treatment, respectively. The NRS scores of the two-step irradiance group were significantly lower than that of the control group (p < .001), with a low fluence rate inducing less pain compared with a high fluence rate (p < .001). Moreover, when the total fluence accumulated to 57.6 J/cm2 , the pain experienced by patients reached its peak. The NRS score of the urethral orifice group was the highest, and the male external genitalia group was the lowest. The NRS score was at its lowest in the first session and highest in the second session. There was a linear relationship between pain and wart size. Among these influencing factors, the fluence rate had the greatest impact on pain. The two-step irradiance schedule provides better analgesic effects than standard treatment irradiation while showing similar treatment efficacy. Factors that influence pain include high fluence rate, CA at the urethral orifice, second therapy session, wart size, and the interval between CO2 laser and ALA-PDT.


Rhinoplasty and the nasolabial area.
The nasolabial area is important to consider in achieving a satisfactory relationship between the nose and the other features of the face; this will result in a natural-looking nose. However, the importance of the entire nose on a particular face should be kept foremost in mind.


Design, synthesis and biological activity of a pyrrolo [2,1-c][1,4]benzodiazepine (PBD)-distamycin hybrid.
We report the synthesis of a new hybrid 13 which is a combination of the naturally occurring antitumor agent distamycin A 1 and the pyrrolo[2,1-c][1,4]benzodiazepine 11, related to the naturally occurring anthramycin 2. The antitumor activity of the hybrid 13 was tested in vitro and compared to the natural product distamycin 1 and the PBD 11.


Ultra-structure of the oral cavity epithelial cells in white rat after experimental application of Naran S preparation.
The effectiveness of the natural drug--Naran S was studied in the therapy of the topical inflammation of the oral cavity mucous membrane. The experiment was conducted on male Wistar rats that were subjected to induction of inflammatory condition by injecting Freund adjuvant and rinsing oral cavity with the infusion of the drug for the period of 28 days. The analysis of the ultra structure of the epithelium cells was conducted with the use of transmission electron microscope. It was observed that under the influence of the drug, the epithelium undergoes renewal, the cells are joined with thick desmosomes, the nuclei have the proper areolas and the mitochondrium matrix is not oedematic.


Clinical and Radiographic Evaluation of Short Locking-Taper Implants Supporting Single Crowns in the Posterior Region: A 12-Year Retrospective Study.
Few studies have reported the outcomes of short implants with a follow-up time > 10 years. This retrospective study aimed to evaluate the long-term outcomes of short locking-taper implants supporting single crowns in the posterior region. Patients who received these supporting implants (≤ 8 mm) in the posterior region from 2008 to 2010 were included. The clinical and radiographic outcomes and patient satisfaction were recorded. A total of 18 patients with 34 implants were included. The cumulative survival rate was 91.4% and 83.3% at implant and patient levels, respectively. Tooth brushing habit and history of periodontitis were significantly associated with implant failure (P < .05). The median marginal bone loss (MBL) was 0.24 mm (IQR: 0.01 to 0.98 mm). Biologic and technical complications occurred in 14.7% and 17.8% of implants, respectively. The mean modified Sulcus Bleeding Index was 0.52 ± 0.63, and the mean peri-implant probing depth was 2.38 ± 0.79 mm. All patients were at least quite satisfied, with the majority of patients (88.9%) being fully satisfied with the treatment. Within the limitations of this study, the short locking-taper implants supporting single crowns in the posterior region achieved promising outcomes in the long-term follow-up.


The SWI/SNF complex member SMARCB1 supports lineage fidelity in kidney cancer.
Lineage switching can induce therapy resistance in cancer. Yet, how lineage fidelity is maintained and how it can be lost remain poorly understood. Here, we have used CRISPR-Cas9-based genetic screening to demonstrate that loss of SMARCB1, a member of the SWI/SNF chromatin remodeling complex, can confer an advantage to clear cell renal cell carcinoma (ccRCC) cells upon inhibition of the renal lineage factor PAX8. Lineage factor inhibition-resistant ccRCC cells formed tumors with morphological features, but not molecular markers, of neuroendocrine differentiation. SMARCB1 inactivation led to large-scale loss of kidney-specific epigenetic programs and restoration of proliferative capacity through the adoption of new dependencies on factors that represent rare essential genes across different cancers. We further developed an analytical approach to systematically characterize lineage fidelity using large-scale CRISPR-Cas9 data. An understanding of the rules that govern lineage switching could aid the development of more durable lineage factor-targeted and other cancer therapies.


Sulfate-mediated electrooxidation of X-ray contrast media on boron-doped diamond anode.
Recently, electrochemical activation of sulfate ions to sulfate radical species and nonradically activated persulfate has been demonstrated at boron-doped diamond (BDD) anode, which enhanced the electrooxidation kinetics of several persistent contaminants. In this study, we investigated the transformation pathways of two X-ray contrast media (ICM), diatrizoate and iopromide, in electrooxidation at BDD anode using sulfate and inert nitrate anolyte. Sulfate anolyte yielded a seven-fold increase in apparent rate constants for ICM oxidation compared to inert nitrate anolyte, and a two-fold increase for the removal of organic carbon. Higher iodine release was observed in electrooxidation of diatrizoate compared to iopromide. In the case of diatrizoate, around 80% of deiodination efficiency was achieved in both anolytes. Deiodination efficiency of iopromide was somewhat lower in nitrate anolyte (≤75%) and significantly reduced in sulfate anolyte (≤46%) due to a larger steric hindrance of alkyl side chains. Moreover, a considerable lag phase of iopromide deiodination was observed in sulfate anolyte, indicating that initial oxidation reactions took place almost exclusively at the alkyl side chains. Several transformation products (TPs) of ICM were identified in electrooxidation in sulfate anolyte, and only three TPs in the case of nitrate anolyte. The main mechanistic steps in the oxidation of iopromide were H-abstraction and bond cleavage in the alkyl side chains. Diatrizoate was mainly transformed through oxidative cleavage of iodine substituent and inter-molecular cyclization. Two hydroxylamine derivatives of iopromide and a nitro-derivative of diatrizoate were observed in sulfate anolyte. These products have not been reported previously for hydroxyl radical-mediated oxidation of ICM. Given that electron-transfer mechanism is more typical for sulfate than for hydroxyl radicals, formation of hydroxylamine and nitro-derivatives of ICM was assigned to one-electron charge transfer to sulfate radical species and formation of N-centered radicals.


Tuberculosis-associated chylothorax revealing an enlarged lymphatic duct due to tuberculosis lymphadenitis.
A 77-year-old woman presented to our hospital with complaints of persistent cough and low-grade fever for two months. On radiological analysis, she had moderate right-sided pleural effusion with right hilar and subcarinal lymphadenopathies. Thoracentesis showed chylothorax of unknown cause. Bronchoscopy revealed a non-specific inflammatory process. However, thoracoscopic surgery demonstrated a curiously enlarged lymphatic duct with its proximal portion compressed by subcarinal lymphadenopathies, pathologically diagnosed as granulomatous lymphadenitis. Hence, tuberculous lymphadenitis was proven to be the cause of chylothorax. Interestingly, cauterization of the lymphatic duct decreased the total amount of right-sided pleural effusion along with a change in colour from milky yellow to red. These were in favour of tuberculosis (TB)-associated chylothorax with the advent of the TB pleuritis. All symptoms and pleural effusion disappeared after the initiation of anti-tuberculous drugs. The present case showed definite evidence of TB-associated chylothorax development mechanism via compression of the lymphatic duct by mediastinal lymphadenopathies.


Kinetics and clinical significance of human herpesvirus 6 DNA shedding in saliva after allogeneic hematopoietic stem cell transplantation.
Little is known about the kinetics and clinical significance of saliva human herpesvirus-6 (HHV-6) DNA after hematopoietic stem cell transplantation (HSCT). In this observational study, we quantified HHV-6 DNA in serially collected plasma and saliva from allogeneic HSCT recipients. Associations between the status of salivary HHV-6 DNA and the development of HHV-6 encephalitis, depression, and oral mucosal graft-versus-host disease (GVHD) were retrospectively analyzed. A total of 787 plasma and 434 saliva samples were collected from 56 patients. The cumulative incidence of HHV-6 DNA in plasma and saliva at 60 days after transplantation was 51.8% and 83.9%, respectively. The peak level of salivary HHV-6 DNA was significantly higher in patients who displayed plasma HHV-6 DNA than in those who did not (median, 51,584 copies/mL vs 587 copies/mL; P < .0001). Salivary HHV-6 DNA levels increased after positive plasma HHV-6 DNA was detected and remained high during observation period. Despite the frequent occurrence of positive salivary HHV-6 DNA, no patient developed depression. Positivity of salivary HHV-6 DNA was not significantly associated with the development of HHV-6 encephalitis (P = 1.00, Fisher's exact test) or oral mucosal GVHD (P = .71, Grey's test). No significant relationship between salivary HHV-6 DNA and these diseases was found even when comparing higher HHV-6 DNA loads in saliva. Salivary HHV-6 DNA levels increased after HHV-6 DNA was detected in the blood. However, no epidemiological evidence was shown to support a role of salivary HHV-6 in the development of HHV-6 encephalitis, depression, and oral mucosal GVHD.


Towards a hand-held, fast, and sensitive gas chromatograph-ion mobility spectrometer for detecting volatile compounds.
Ion mobility spectrometers can detect gaseous compounds at atmospheric pressure in the range of parts per trillion within a second. Due to their fast response times, high sensitivity, and limited instrumental effort, they are used in a variety of applications, especially as mobile or hand-held devices. However, most real-life samples are gas mixtures, which can pose a challenge for IMS with atmospheric pressure chemical ionization mainly due to competing gas-phase ionization processes. Therefore, we present a miniaturized drift tube IMS coupled to a compact gas chromatograph for pre-separation, built of seven bundled standard GC columns (Rtx-Volatiles, Restek GmbH) with 250 μm ID and 1.07 m in length. Such pre-separation significantly reduces chemical cross sensitivities caused by competing gas-phase ionization processes and adds orthogonality. Our miniaturized GC-IMS system is characterized with alcohols, halocarbons, and ketones as model substances, reaching detection limits down to 70 pptv with IMS averaging times of just 125 ms. It separates test mixtures of ketones and halocarbons within 180 s and 50 s, respectively. The IMS has a short drift length of 40.6 mm and reaches a high resolving power of RP = 68. Graphical abstract.


The 2013 cholesterol guideline controversy: Would better evidence prevent pharmaceuticalization?
Cardiovascular disease (CVD) remains the leading cause of death globally. A class of medications, known as statins, lowers low-density lipoprotein cholesterol levels, which are associated with CVD. The newest 2013 U.S. cholesterol guideline contains an assessment of risk that greatly expands the number of individuals without CVD for whom statins are recommended. Other countries are also moving in this direction. This article examines the controversy surrounding these guidelines using the 2013 cholesterol guidelines as a case study of broader trends in clinical guidelines to use a narrow evidence base, expand the boundaries of disease and overemphasize pharmaceutical treatment. We find that the recommendation in the 2013 cholesterol guidelines to initiate statins in individuals with a lower risk of CVD is controversial and there is much disagreement on whether there is evidence for the guideline change. We note that, in general, clinical guidelines may use evidence that has a number of biases, are subject to conflicts of interest at multiple levels, and often do not include unpublished research. Further, guidelines may contribute to the "medicalization" or "pharmaceuticalization" of healthcare. Specific policy recommendations to improve clinical guidelines are indicated: these include improving the evidence base, establishing a public registry of all results, including unpublished ones, and freeing the research process from pharmaceutical sector control.


Bitter and sweet components of ethanol taste in humans.
This study examined taste descriptions elicited by ethanol and by other tastants in humans. All subjects described 10% ethanol as bitter and approximately 30% of the subjects described it as sweet and/or sour. Highly significant correlations were found between sweetness of some sucrose solutions (0.6-1%) and intensity of the taste of ethanol. In another experiment, quinine (bitter) solutions were rated as similar to 10% ethanol taste and this effect was potentiated by the addition of sucrose. In contrast, citric acid (sour) tended to decrease similarity ratings when added to the quinine solutions. Taken together, these findings suggest that: (1) in humans ethanol tastes both bitter and sweet; and (2) the relationship between sucrose and ethanol intakes previously found in animals and humans may result, at least partially, from similar taste responses elicited by sucrose and ethanol.


A novel enrichment approach for anaerobic digestion of lignocellulosic biomass: Process performance enhancement through an inoculum habitat selection.
Inocula enrichment was performed using an innovative habitat-based selection approach to improve wheat straw (WS) anaerobic digestion (AD) efficiency. The procedure was carried out by sequentially re-inoculating the primary microbial community seven times in subsequent anaerobic reactors containing untreated WS. Re-inocula were performed at different re-inoculum times (24, 48, and 96 h) by moving a porous support mimicking a rumen structure from one batch to the next (S-tests) or re-inoculating only the culture medium (C-tests). Highest H2 production yields were observed after four and five re-inocula (0.08 ± 0.02 NmL h-1 gVS-1 and 0.09 ± 0.02 NmL h-1 gVS-1) for S-24 and S-48, respectively. For S-96, higher CH4 yields were observed after the start-up test and sixth re-inoculum (0.05 ± 0.003 NmL h-1 gVS-1 and 0.04 ± 0.005 NmL h-1 gVS-1, respectively). Accordingly, S-96 showed the highest active Archaea component (7%). C-test microbial communities were dominated by fermenting, hydrogen-producing bacteria and showed lower microbial community diversity than S-tests.


[Intermittent catheterization in children with neurogenic bladder].
Urinary tract infection and incontinence can be treated with intermittent Catheterization, routine bladder studies should be began. The infection of the upper urine tract is going down, the social continence is going on.


Optimizing MRF-ASL scan design for precise quantification of brain hemodynamics using neural network regression.
Arterial Spin Labeling (ASL) is a quantitative, non-invasive alternative for perfusion imaging that does not use contrast agents. The magnetic resonance fingerprinting (MRF) framework can be adapted to ASL to estimate multiple physiological parameters simultaneously. In this work, we introduce an optimization scheme to increase the sensitivity of the ASL fingerprint. We also propose a regression based estimation framework for MRF-ASL. To improve the sensitivity of MRF-ASL signals to underlying parameters, we optimized ASL labeling durations using the Cramer-Rao Lower Bound (CRLB). This paper also proposes a neural network regression based estimation framework trained using noisy synthetic signals generated from our ASL signal model. We tested our methods in silico and in vivo, and compared with multiple post labeling delay (multi-PLD) ASL and unoptimized MRF-ASL. We present comparisons of estimated maps for the six parameters of our signal model. The scan design process facilitated precise estimates of multiple hemodynamic parameters and tissue properties from a single scan, in regions of normal gray and white matter, as well as regions with anomalous perfusion activity in the brain. In particular, there was a 86.7% correlation of perfusion estimates with the ground truth in silico, using our proposed techniques. In vivo, there was roughly a 7 fold improvement in the Coefficient of Variation (CoV) for white matter perfusion, and 2 fold improvement in gray matter perfusion CoV in comparison to a reference Multi PLD method. The regression based estimation approach provided perfusion estimates rapidly, with estimation times of around 1s per map. Scan design optimization, coupled with regression-based estimation is a powerful tool for improving precision in MRF-ASL.


Expanding the application of haplotype-based genomic predictions to the wild: A case of antibody response against Teladorsagia circumcincta in Soay sheep.
Genomic prediction of breeding values (GP) has been adopted in evolutionary genomic studies to uncover microevolutionary processes of wild populations or improve captive breeding strategies. While recent evolutionary studies applied GP with individual single nucleotide polymorphism (SNP), haplotype-based GP could outperform individual SNP predictions through better capturing the linkage disequilibrium (LD) between the SNP and quantitative trait loci (QTL). This study aimed to evaluate the accuracy and bias of haplotype-based GP of immunoglobulin (Ig) A (IgA), IgE, and IgG against Teladorsagia circumcincta in lambs of an unmanaged sheep population (Soay breed) based on Genomic Best Linear Unbiased Prediction (GBLUP) and five Bayesian [BayesA, BayesB, BayesCπ, Bayesian Lasso (BayesL), and BayesR] methods. The accuracy and bias of GPs using SNP, haplotypic pseudo-SNP from blocks with different LD thresholds (0.15, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1.00), or the combinations of pseudo-SNPs and non-LD clustered SNPs were obtained. Across methods and marker sets, higher ranges of genomic estimated breeding values (GEBV) accuracies were observed for IgA (0.20 to 0.49), followed by IgE (0.08 to 0.20) and IgG (0.05 to 0.14). Considering the methods evaluated, up to 8% gains in GP accuracy of IgG were achieved using pseudo-SNPs compared to SNPs. Up to 3% gain in GP accuracy for IgA was also obtained using the combinations of the pseudo-SNPs with non-clustered SNPs in comparison to fitting individual SNP. No improvement in GP accuracy of IgE was observed using haplotypic pseudo-SNPs or their combination with non-clustered SNPs compared to individual SNP. Bayesian methods outperformed GBLUP for all traits. Most scenarios yielded lower accuracies for all traits with an increased LD threshold. GP models using haplotypic pseudo-SNPs predicted less-biased GEBVs mainly for IgG. For this trait, lower bias was observed with higher LD thresholds, whereas no distinct trend was observed for other traits with changes in LD. Haplotype information improves GP performance of anti-helminthic antibody traits of IgA and IgG compared to fitting individual SNP. The observed gains in the predictive performances indicate that haplotype-based methods could benefit GP of some traits in wild animal populations.


Characteristics influencing career decisions of academic and nonacademic emergency physicians.
To determine characteristics motivating physicians to choose careers in academic and nonacademic emergency medicine. A written survey of 1,017 active members of the Society for Academic Emergency medicine and of a random sample of 2,000 members of the American College of Emergency Physicians was performed. Questions were asked regarding medical school, residency, and fellowship training; the importance of specific factors in influencing career decisions; and perceived obstacles to emergency medicine research. Responses from nonfaculty and adjunct, clinical, and research faculty were compared using chi 2 analysis for discrete variables and a four-group analysis of variance for continuous variables. None. Responses were obtained from 1,203 physicians (41.3%). Those choosing academic careers were significantly more likely to complete a residency in emergency medicine or internal medicine and fellowship training in research or toxicology compared with nonacademic physicians. Nonfaculty and clinical faculty considered family obligations, leisure time, and personal income to be the most important factors influencing their career decisions; research faculty considered role models and the value of research to be most important. There was no difference in indebtedness among the groups. Finding time and funding, administrative obligations, and pressures to do clinical work were the most important obstacles to research productivity. Factors influencing career decisions can be used to plan strategies to meet the future needs of academic emergency medicine.


Do habitat and elevation promote hybridization during secondary contact between three genetically distinct groups of warbling vireo (Vireo gilvus)?
Following postglacial expansion, secondary contact can occur between genetically distinct lineages. These genetic lineages may be associated with specific habitat or environmental variables and therefore, their distributions in secondary contact could reflect such conditions within these areas. Here we used mtDNA, microsatellite, and morphological data to study three genetically distinct groups of warbling vireo (Vireo gilvus) and investigate the role that elevation and habitat play in their distributions. We studied two main contact zones and within each contact zone, we examined two separate transects. Across the Great Plains contact zone, we found that hybridization between eastern and western groups occurs along a habitat and elevational gradient, whereas hybridization across the Rocky Mountain contact zone was not as closely associated with habitat or elevation. Hybrids in the Great Plains contact zone were more common in transitional areas between deciduous and mixed-wood forests, and at lower elevations (<1000 m). Hybridization patterns were similar along both Great Plains transects indicating that habitat and elevation play a role in hybridization between distinct eastern and western genetic groups. The observed patterns suggest adaptation to different habitats, perhaps originating during isolation in multiple Pleistocene refugia, is facilitating hybridization in areas where habitat types overlap.


The management of predicted ovarian hyperstimulation involving gonadotropin-releasing hormone analog with elective cryopreservation of all pre-embryos.
Severe ovarian hyperstimulation syndrome complicates up to 6% of IVF treatment cycles. We have utilized our pre-embryo cryopreservation program to manage incipient ovarian hyperstimulation syndrome in an alternative way. Four women, who were at risk of developing ovarian hyperstimulation syndrome, underwent oocyte retrieval, but not embryo replacement. Instead, resulting pre-embryos were cryopreserved for future transfer. The four patients have since become pregnant. Three conceived after thawed embryo replacement cycles, and the fourth conceived spontaneously 1 month after the stimulation cycle. This approach offers maximum flexibility in the management of ovarian hyperstimulation syndrome.


Hypofractionated radiotherapy with temozolomide in diffuse intrinsic pontine gliomas: a randomized controlled trial.
Diffuse intrinsic pontine glioma (DIPG) is the most common form of brainstem glioma. The present study was performed to assess if hypofractionated radiotherapy completed in < 3 weeks with temozolomide improves survival in DIPG. The present study is a phase II open label randomized trial. The study included newly diagnosed patients with DIPG. Patients in arm A received conventional fractionated RT of 60 Gy in 30 fractions over 6 weeks while patients in arm B received hypo-fractionated radiotherapy of 39 Gy in 13 fractions over 2.6 weeks along with concurrent Temozolomide (TMZ) 75 mg/m2 from day 1 to day 17 followed by adjuvant TMZ for six cycles. The survival analysis was performed with modified intention to treat analysis. A total of 35 patients were randomized. 33 patients were evaluable. 93% (n = 14) of patients in the conventional arm completed treatment while only 17% (n = 3) of the children could complete planned course of treatment in the experimental arm. The median overall survival (OS) was 11 months (95% CI - 7.5 to 14.5 months) in the conventional arm and 12 months (95% CI - 10.5 to 13.5 months) in the experimental arm (p = 0.208). 28% (n = 5) patients in the experimental arm developed grade 3 or 4 hematological toxicity. The above study shows that hypofractionated radiotherapy with concurrent and adjuvant temozolomide does not improve OS and has higher hematological toxicity. Conventional radiotherapy remains the standard of care.


Exploring static and dynamic relationships between burden of disease and research funding in the United States.
The relationship between burden of disease and research funding has been examined cross-sectionally, but temporal patterns have not been investigated. It is logical to assume that temporal improvements in disability-adjusted life-years (DALYs) reflect benefits from research funding; such assumptions are tempered by an unknown lag time for emergence of benefits from research. We studied National Institutes of Health (NIH) research fund allocations and United States DALY estimates for overlapping disease categories (matched disease categories, MDC, N = 38). Using a general linear model, we separately analysed DALYs for MDCs in 2017 in relation to NIH research allocations in 2017 and 2007. We also examined how changes in DALYs were related to cumulative NIH research funding (2006-2017). After regressing DALY change on summed funding, we obtained model residuals as estimates of the discrepancy for each MDC between observed and expected change in burden, given funding. In 2017, there was a positive association between NIH research fund allocations and DALYs for the same year (F1,36 = 16.087, p = 0.0002921; slope = 0.35020; model R2 = 0.3088), suggesting proportionate allocation. There was a positive association between 2017 DALYs and 2007 NIH research allocation, implying a beneficial impact of research (F1,36 = 15.754, p = 0.0003; slope = 0.8845; model R2 = 0.3044). In contrast, there was a nonsignificant association between summed NIH funding and percent change in DALYs over 2006-2017 (F1,36 = 0.199; p = 0.65; beta coefficient = -1.144). When MDCs were ordered based on residuals, HIV/AIDS ranked first. Mental, neurologic or substance abuse (MNS) disorders comprised most residuals in the lower half. NIH fund allocation is proportional to DALYs for MDCs. Temporal changes in DALYs vary by MDCs, but they are not significantly related to cumulative research outlays. Further analysis of temporal changes in DALYs could help to inform research outlays for MDCs and to study the impact of research.


Tau underlies synaptic and cognitive deficits for type 1, but not type 2 diabetes mouse models.
Diabetes mellitus (DM) is one of the most devastating diseases that currently affects the aging population. Recent evidence indicates that DM is a risk factor for many brain disorders, due to its direct effects on cognition. New findings have shown that the microtubule-associated protein tau is pathologically processed in DM; however, it remains unknown whether pathological tau modifications play a central role in the cognitive deficits associated with DM. To address this question, we used a gain-of-function and loss-of-function approach to modulate tau levels in type 1 diabetes (T1DM) and type 2 diabetes (T2DM) mouse models. Our study demonstrates that tau differentially contributes to cognitive and synaptic deficits induced by DM. On one hand, overexpressing wild-type human tau further exacerbates cognitive and synaptic impairments induced by T1DM, as human tau mice treated under T1DM conditions show robust deficits in learning and memory processes. On the other hand, neither a reduction nor increase in tau levels affects cognition in T2DM mice. Together, these results shine new light onto the different molecular mechanisms that underlie the cognitive and synaptic impairments associated with T1DM and T2DM.


Tuning selectivity in macrotricyclic carbohydrate receptors; CH-->N mutations in aromatic spacers.
Dipicolinoyl spacer groups are used to control the conformational and H-bonding properties of tricyclic carbohydrate receptors 3 and 4. Binding selectivities are changed in relation to all-isophthaloyl system 1b.


Are phosphodiesterase Type 5 inhibitors potential therapies for Alzheimer's disease and related dementias?
This scientific commentary refers to 'No association between initiation of phosphodiesterase-5 inhibitors and risk of incident Alzheimer's disease and related dementia: results from the Drug Repurposing for Effective Alzheimer's Medicines (DREAM) study' by Desai et al. (https://doi.org/10.1093/braincomms/fcac247).


The association of feeding difficulties and generic health-related quality of life among children born with esophageal atresia.
Children born with esophageal atresia experience feeding difficulties. This study investigates the association of feeding difficulties and generic health-related quality of life among children aged 2-7 and 8-17 years, born with esophageal atresia. 108 families (n = 36 aged 2-7 years; n = 72 aged 8-17) answered a survey regarding difficulties in their child's mealtimes and a validated generic health-related quality of life instrument(PedsQL 4.0). Clinical data was collected from hospital records. The association of feeding difficulties and health-related quality of life was analysed trough Mann-Whitney U-test. Linear regression determined whether the number of concurrent feeding difficulties in the child decreased the health-related quality of life scores. P < 0.05 was considered significant. In children aged 2-7 and 8-17 years, to have a gastrostomy, to use a food infusion pump, need for energy-enriched food and eating small portions were respectively significantly associated with lower total health-related quality of life scores in the parent-reports (p < 0.05). Most of the feeding difficulties had a negative significant relationship with the domains of physical and social functioning. Additionally, in the older age group, long mealtimes and adult mealtime supervision were associated with lower scores in both child and parent reports. In both age groups, an increased number of feeding difficulties in the child decreased the total generic health-related quality of life scores (p < 0.01). Specific feeding difficulties are associated with low health-related quality of life among children with esophageal atresia. An increasing number of feeding difficulties is associated to decreasing health-related quality of life-scores. Further research is needed to understand these associations.


Enhancement of bone consolidation in mandibular distraction osteogenesis: a contemporary review of experimental studies involving adjuvant therapies.
One of the major disadvantages of mandibular distraction osteogenesis (MDO) is the prolonged time required for consolidation of the regenerate bone. The objective of the present study is to perform a contemporary review of various adjuvant therapies to enhance bone consolidation in MDO. A PubMed search for articles related to MDO, along with the references of those articles, was performed. Inclusion and exclusion criteria were applied to all experimental studies assessing adjuvant therapies to enhance bone consolidation. A total of 1414 titles and abstracts were initially reviewed; 61 studies were included for full review. Many studies involved growth factors, hormones, pharmacological agents, gene therapy, and stem cells. Other adjuvant therapies included mechanical stimulation, laser therapy, and hyperbaric oxygen. Majority of the studies demonstrated positive bone healing effects and thus adjuvant therapies remain a viable strategy to enhance and hasten the consolidation period. Although most studies have demonstrated promising results, many questions still remain, such as optimal amount, timing, and delivery methods required to stimulate the most favorable bone regeneration. As well, further studies comparing various adjuvant therapies and documentation of long-term adverse effects are required prior to clinical application.


Perception of random-dot symmetry and apparent movement at and near isoluminance.
There have been conflicting reports on whether apparent movement in random-dot kinematograms is abolished at isoluminance. The present results suggest that it is, provided that dynamic (uncorrelated) surrounds are used, and the subject has to report the shape of the target rather than the presence of movement in an isolated portion of the target. On the other hand, perception of random-dot symmetry is still possible at isoluminance. The reason for this difference appears to be the need for exact-position information in movement but not symmetry perception. Control experiments suggest that the effects are not due to artefacts such as chromatic aberration in the eye.


A mitotic NADPH upsurge promotes chromosome segregation and tumour progression in aneuploid cancer cells.
Redox metabolites have been observed to fluctuate through the cell cycle in cancer cells, but the functional impacts of such metabolic oscillations remain unknown. Here, we uncover a mitosis-specific nicotinamide adenine dinucleotide phosphate (NADPH) upsurge that is essential for tumour progression. Specifically, NADPH is produced by glucose 6-phosphate dehydrogenase (G6PD) upon mitotic entry, which neutralizes elevated reactive oxygen species (ROS) and prevents ROS-mediated inactivation of mitotic kinases and chromosome missegregation. Mitotic activation of G6PD depends on the phosphorylation of its co-chaperone protein BAG3 at threonine 285, which results in dissociation of inhibitory BAG3. Blocking BAG3T285 phosphorylation induces tumour suppression. A mitotic NADPH upsurge is present in aneuploid cancer cells with high levels of ROS, while nearly unobservable in near-diploid cancer cells. High BAG3T285 phosphorylation is associated with worse prognosis in a cohort of patients with microsatellite-stable colorectal cancer. Our study reveals that aneuploid cancer cells with high levels of ROS depend on a G6PD-mediated NADPH upsurge in mitosis to protect them from ROS-induced chromosome missegregation.


Left ventricular mechanoreceptors: a haemodynamic study.
1. To study the function of the left ventricular mechanoreceptors, a working left ventricle preparation was devised in dogs which permitted control of pressure and flow of the isolated perfused coronary circulation and of the flow of the isolated, separately perfused systemic circulation. The systemic circulation was perfused at a constant rate so that changes in systemic pressure reflected changes in systemic resistance.2. Increases in myocardial contractility produced by injection of catecholamines into the isolated, perfused coronary circulation produced a fall in the pressure (resistance) of the isolated, separately perfused (at a constant rate) systemic circulation.3. Completeness of isolation of the coronary and systemic circulations was shown by the marked difference in appearance times between the reflex hypotensive responses from catecholamine injections into the isolated coronary circulation and the direct hypertensive response from a similar injection when the circulations were connected as well as by the marked difference between the pressure pulses recorded simultaneously on both sides of the aortic balloon separating the two circulations.4. Myocardial beta receptor blockade produced by injection of propranolol into the isolated coronary circulation abolished or attenuated the changes in left ventricular myocardial contractility as well as the subsequent hypotensive responses following the similar injection of catecholamines.5. Electrical stimulation of a sympathetic nerve innervating the heart resulted in increases in left ventricular myocardial contractility and subsequent systemic hypotensive responses indistinguishable from those following injection of catecholamines.6. That distortion of the mechano- or stretch receptors in the left ventricular myocardium was the cause of the hypotensive responses was demonstrated by increasing left ventricular myocardial contractility by mechanically obstructing the left ventricular outflow which produced hypotensive responses similar to those following the injection of catecholamines or nerve stimulation.7. Bilateral high cervical vagotomy abolished the hypotensive responses following injection of catecholamines into the isolated coronary circulation or following left ventricular outflow obstruction in all but one instance, indicating the importance of vagal fibres to the afferent arm of the reflex.8. It is suggested that the left ventricular mechanoreceptors function normally to reduce the peripheral resistance in order to prepare the systemic circulation to receive the left ventricular output and, especially during exercise, to prepare the systemic circulation to receive the augmented cardiac output with a minimum alteration in the systemic blood pressure and to distribute this augmented output preferentially to the skeletal muscles.


Air temperature and incidence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.
Higher outdoor temperature may be related to an increase in antibiotic resistant bacteria. We investigated the association between local outdoor air temperature and the incidence of extended-spectrum betalactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) correcting for known drivers of antibiotic resistance. We performed a time-series regression study using prospectively collected weekly surveillance data on all ESBL-PE isolated from in- and outpatients of the University Hospital Basel, a tertiary care center in Switzerland, between 01/2008-12/2017. Temperature was measured hourly at the meteorological institute of the University Basel next to our institution over this time period. A time-series approach using a Poisson regression model and different lag terms for delayed exposure effects was performed to assess associations between minimal, mean and maximal weekly temperature and the number of ESBL-PE recovered. Over 10 years, recovery of ESBL-PE increased (annual incidence rate ratio [IRR] 1.14, 95%CI 1.13-1.16), while mean weekly temperature measures remained stable. In multivariable analyses, increasing temperature was associated with higher recovery rates of ESBL-PE after three to four weeks, correcting for potential confounders, such as the number of admissions, proportion of long-term nursing facility- and ICU-admissions, age, Charlson comorbidity index and consumption of antimicrobials (IRRs per 10 °C ranging from 1.14 to 1.22, 95%CIs 1.07-1.33). These trends remained when analyzing correlations between temperature with the proportion of extended spectrum cephalosporin resistance of all recovered Enterobacteriaceae. Higher outdoor temperature may be associated with an increase of ESBL-PE-incidence, independent of important confounders, such as antimicrobial consumption and thus should be considered for future resistance-trajectories.


Underdiagnosed and uncontrolled asthma: findings in rural schoolchildren from the Delta region of Arkansas.
Studies of asthma in school-aged rural children in the United States are limited, and there are no studies of high-risk pediatric populations in rural environments. To examine the prevalence of asthma and to evaluate markers of morbidity in 2 rural school districts in the Arkansas Delta region. Children at risk for asthma were identified by using a cross-sectional asthma case-finding survey. Surveys were distributed to students enrolled in the Marvell and Eudora school districts during the 2005-2006 school year. The response rate was 81% (964 of 1,190). The mean age of the 964 children who completed the survey was 10.3 years (age range, 4-17 years); 85% were African American, and 78% had state-issued insurance. Twenty-eight percent (268 of 964) of the children were categorized as being at risk for asthma by previous physician diagnosis (33%), algorithm diagnosis (16%), or both (51%). Of the 268 at-risk children, 79% reported persistent symptoms and 21% reported intermittent or no current symptoms. In the previous 4 weeks, 59% of the children experienced daytime and nocturnal symptoms and 62% used rescue medications. Activity limitation and treatment in the emergency department or hospitalization for asthma in the previous 2 years were reported by 82% and 49% of the children, respectively. Active asthma symptoms are prevalent in this predominantly minority, low-income, rural population. High rates of undiagnosed and uncontrolled asthma are suggested by frequent asthma symptoms, activity limitation, rescue medication use, and emergency health care utilization. Future studies of pediatric asthma should focus on high-risk populations in rural locales.


Differences in the duration of the enhancement of liver mixed-function oxidase activities in ethanol-fed rats after withdrawal.
Liver microsomal mixed-function oxidase activities were determined in female Sprague-Dawley rats after 3 weeks of ethanol feeding and for up to 10 days after withdrawal. Ethanol (36% of total calories) was administered in a high fat liquid diet and was replaced isocalorically by carbohydrates in controls. Chronic ethanol feeding similarly enhanced both microsomal cytochrome P-450 content and benzphetamine N-demethylase activity, per mg of protein, and resulted in a disproportionate increase in both aniline hydroxylase and 7-ethoxycoumarin O-deethylase activities. A 6- to 7-day withdrawal period was apparently necessary for the overall disappearance of these effects of ethanol. Marked differences, however, were seen in the time courses of return of these variables to control levels, as also indicated by changes, during this period and specially during the first 24 hr after withdrawal, in the apparent molar activity of the microsomal fraction with the three substrates tested. The results were interpreted as indicating that the distinct ethanol-inducible cytochrome P-450 isozyme, with a high specific activity toward aniline, undergoes a very rapid turnover in liver microsomes. Induction of another form of cytochrome P-450, differing from the former by its slower turnover rate, would explain the induction by ethanol of 7-ethoxycoumarin O-deethylase activity. The withdrawal of ethanol was followed by a rapid but transient increase in benzphetamine N-demethylase activity above the ethanol-induced level, at a time when other activities were rapidly declining. This could suggest that the microsomal content of other cytochrome P-450 isozyme(s), with high specific activity toward this substrate, would also be temporarily altered during ethanol withdrawal. Important alterations in microsomal cytochrome P-450-dependent mixed-function oxidase activities occurred during the initial 24-hr period of withdrawal, even in the absence of a change in microsomal cytochrome P-450 content, indicating that the effects of chronic ethanol ingestion on hepatic drug-metabolizing enzyme activities may also be highly dependent on the proximity of ethanol intake.


Expert opinion and patients' in-depth interviews on the impact of pulmonary complications in systemic sclerosis.
To qualitatively explore the perceptions and opinions of experts dealing with systemic sclerosis (SSc) and patients with SSc on the impact of the disease and pulmonary complications on economic status, psycho-social wellbeing and the diagnostic and therapeutic journey, and to identify which strategies/interventions may be useful to address patients' and their family's needs. An expert meeting was conducted using the NGT to discuss the consequences of pulmonary complications on the Italian SSc community. The direct experience of five patients with SSc and pulmonary complications was described through in-depth interviews conducted by psychologists. The experts' meeting and patients' in-depth interviews underline the complexity of SSc and the consequences of pulmonary involvement on patients' and caregivers' health-related quality of life, working ability, psychological wellbeing and social interactions. Panellists suggest that improved communication between physicians, associations and institutions could help protect the working status of patients with SSc. Granting patients disability benefits, providing access to part-time jobs and productivity-focused training could also help decrease the economic burden of the disease. A multidisciplinary approach is recommended to reduce treatment burden, together with the implementation of standard diagnostic and therapeutic paths and increased use of telemedicine via platforms that ensure secure health data sharing. Both patients and caregivers may benefit from psychological support. SSc and pulmonary fibrosis have profound consequences on patients' and caregivers' health-related quality of life, working ability, psychological wellbeing and social interactions. Some activities may help patients and families deal with these aspects of the disease.


Adaptation of Phaeobacter inhibens DSM 17395 to growth with complex nutrients.
Phaeobacter inhibens DSM 17395, a member of the Roseobacter clade, was studied for its adaptive strategies to complex and excess nutrient supply, here mimicked by cultivation with Marine Broth (MB). During growth in process-controlled fermenters, P. inhibens DSM 17395 grew faster (3.6-fold higher μmax ) and reached higher optical densities (2.2-fold) with MB medium, as compared to the reference condition of glucose-containing mineral medium. Apparently, in the presence of MB medium, metabolism was tuned to maximize growth rate at the expense of efficiency. Comprehensive proteomic analysis of cells harvested at ½ ODmax identified 1783 (2D DIGE, membrane and extracellular protein-enriched fractions, shotgun) different proteins (50.5% coverage), 315 (based on 2D DIGE) of which displayed differential abundance profiles. Moreover, 145 different metabolites (intra- and extracellular combined) were identified, almost all of which (140) showed abundance changes. During growth with MB medium, P. inhibens DSM 17395 specifically formed the various proteins required for utilization of phospholipids and several amino acids, as well as for gluconeogenesis. Metabolic tuning on amino acid utilization is also reflected by massive discharge of urea to dispose the cell of excess ammonia. Apparently, P. inhibens DSM 17395 modulated its metabolism to simultaneously utilize diverse substrates from the complex nutrient supply.


In vivo analysis of angiogenesis in endometriosis-like lesions by intravital fluorescence microscopy.
To establish a novel endometriosis model that allows for repetitive in vivo analyses of angiogenesis in ectopic endometrial tissue. Intravital fluorescence microscopic study. Institute for Clinical and Experimental Surgery, University of Saarland. Female Syrian golden hamsters equipped with skinfold chambers. Large (0.5 mm2) and small (0.1 mm2) endometrial fragments were mechanically isolated and transplanted autologously into skinfold chambers of untreated hormonally synchronized or bilaterally ovariectomized hamsters. Angiogenesis, vascularization, and microhemodynamics were analyzed over a 14-day period. In untreated controls, endometrial fragments developed complete microvascular networks during the experimental observation period. Interestingly, microvascular blood flow was higher in large than in small fragments. Histologic examinations revealed proliferating endometriosis-like lesions with dilated endometrial glands surrounded by a richly vascularized stroma. Vascularization of endometrial fragments in synchronized animals did not differ from that of untreated controls. In contrast, endometrial fragments in ovariectomized animals showed a delay in angiogenesis and a significantly decreased blood perfusion, indicating the essential role of ovarian estrogens for ectopic vascularization and perfusion of endometrial tissue. This novel model of endometrial tissue transplantation is a useful experimental approach, not only to focus on the in vivo pathogenesis of endometriosis but also to develop antiangiogenic strategies for the treatment of this disease.


Clinical Outcomes of B Cell Acute Lymphoblastic Leukemia Patients Treated with Haploidentical Stem Cells Combined with Umbilical Cord Blood Transplantation.
Clinical outcomes of hematopoietic stem cell transplantation (HSCT) using a haploidentical stem cell graft and an unrelated umbilical cord blood unit (haplo-cord HSCT) for the treatment of B cell acute lymphoblastic leukemia (B-ALL) remain unclear. This study was conducted to explore the clinical outcomes of haplo-cord HSCT in patients with B-ALL. A total of 112 B-ALL patients who underwent haplo-cord HSCT and 64 B-ALL patients who underwent haploidentical HSCT (haplo-HSCT) at our center between 2010 and 2020 were retrospectively included in this study, and clinical outcomes and prognostic factors were further analyzed. Of the 112 haplo-cord HSCT recipients, 106 (94.6%) achieved complete haploidentical chimerism and 6 (5.4%) had mixed cord blood chimerism. No differences in neutrophil and platelet recovery or in the incidences of graft-versus-host disease, cytomegalovirus/Epstein-Barr virus viremia, bloodstream infection, or hemorrhagic cystitis were observed between the haplo-cord HSCT and haplo-HSCT groups. Compared with the haplo-HSCT group, the haplo-cord HSCT group had a higher absolute number of CD3+ cells (P = .029) and a lower ratio of CD3+CD4+ /CD3+CD8+ cells (P = .049) at 1 month post-transplantation. Moreover, the haplo-cord HSCT group had lower minimal residual disease (MRD) levels at 1 month (P = .020) and 100 days (P = .038) post-transplantation and a better 3-year prognosis (overall survival, P = .016; disease-free survival, P = .041; cumulative incidence of relapse [CIR], P = .016). The CIRs in patients with adverse genomic features (P = .040) or flow cytometry-based MRD (FCM-MRD) ≥1 × 10-4 (P = .033) were improved by haplo-cord HSCT. Multivariate analysis revealed that haplo-cord HSCT could independently improve the 3-year OS, DFS, and CIR of B-ALL patients (OS, P = .029; DFS, P = .024; CIR, P = .024). In addition, allo-HSCT at first complete remission was an independent parameter associated with 3-year OS for B-ALL patients (P = .014). An FCM-MRD ≥1 × 10-4 pre-HSCT could independently predict unfavorable 3-year DFS and CIR (DFS, P = .020; CIR, P = .036) in B-ALL patients. Our data suggest that the use of haplo-cord HSCT can independently improve survival in patients with B-ALL.


Transcriptome sequencing analysis of porcine MDM response to FSL-1 stimulation.
Mycoplasma infection can cause many diseases in pigs, resulting in great economic losses in pork production. Innate immune responses are thought to play critical roles in the pathogenesis of mycoplasma disease. However, the molecular events involved in immune responses remain to be determined. Hence, the object of this study was to use RNA-Seq to investigate the gene expression profiles of the innate immune response mediated by FSL-1 in pig monocyte-derived macrophages (MDMs). The results revealed that 1442 genes were differentially expressed in the FSL-1 group compared with the control groups, of which 777 genes were upregulated and 665 genes were downregulated. KEGG pathway analysis showed that the upregulated genes were mainly involved in innate immune-related pathways including the TNF signaling pathway, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, Jak-STAT signaling pathway, chemokine signaling pathway, NOD-like receptor signaling pathway and NF-kappa B signaling pathway. The downregulated genes were only involved in the cGMP-PKG signaling pathway and glycerophospholipid metabolism. Our results showed that FSL-1 stimulation activated the TLR2 signaling pathway and resulted in diverse inflammatory responses. FSL-1 induced the transcription of numerous protein-coding genes involved in a complex network of innate immune-related pathways. We speculate that TNF, IL1B, IL6, NFKB1, NFKBIA, CXCL2, CXCL8, CXCL10, CCL2, CCL4 and CCL5 were the most likely hub genes that play important roles in the above pathways. This study identified the differentially expressed genes and their related signaling pathways, contributing to the comprehensive understanding of the mechanisms underlying host-pathogen interactions during mycoplasma infection and providing a reference model for further studies.


[Parathyroid hormone for disorders of calcium metabolism and metabolic bone diseases other than osteoporosis].
Recombinant human parathyroid hormone (PTH) analogues reduce fractures in patients with osteoporosis by enhancing bone formation and improving bone quality. Furthermore, many studies have demonstrated the efficacy of these analogues in diseases such as PTH-deficient hypoparathyroidism, bisphosphonate-related osteonecrosis of the jaw and hypophosphatasia. Further studies are needed to examine the long-term effects and the safety of these analogues in children and cancer patients.


How we treat NK/T-cell lymphomas.
Natural killer (NK)/T-cell lymphomas are aggressive malignancies with a predilection for Asian and South American populations. Epstein-Barr virus (EBV) infection in lymphoma cells is universal. Predominantly extranodal, NK/T-cell lymphomas are divided clinically into nasal (involving the nose and upper aerodigestive tract), non-nasal (involving the skin, gastrointestinal tract, testes, and other organs), and aggressive leukaemia/lymphoma (involving the marrow and multiple organs) subtypes. Initial assessment should include imaging with positron emission tomography computed tomography (PET/CT), quantification of plasma EBV DNA as a surrogate marker of lymphoma load, and bone marrow examination with in situ hybridization for EBV-encoded small RNA. Prognostication can be based on presentation parameters (age, stage, lymph node involvement, clinical subtypes, and EBV DNA), which represent patient factors and lymphoma load; and dynamic parameters during treatment (serial plasma EBV DNA and interim/end-of-treatment PET/CT), which reflect response to therapy. Therapeutic goals are to achieve undetectable plasma EBV DNA and normal PET/CT (Deauville score ≤ 3). NK/T-cell lymphomas express the multidrug resistance phenotype, rendering anthracycline-containing regimens ineffective. Stage I/II nasal cases are treated with non-anthracycline asparaginase-based regimens plus sequential/concurrent radiotherapy. Stage III/IV nasal, and non-nasal and aggressive leukaemia/lymphoma cases are treated with asparaginase-containing regimens and consolidated by allogeneic haematopoietic stem cell transplantation (HSCT) in suitable patients. Autologous HSCT does not improve outcome. In relapsed/refractory cases, novel approaches comprise immune checkpoint blockade of PD1/PD-L1, EBV-specific cytotoxic T-cells, monoclonal antibodies, and histone deacetylase inhibitors. Future strategies may include inhibition of signalling pathways and driver mutations, and immunotherapy targeting the lymphoma and its microenvironment.


Intrapulmonary perfluorooctyl bromide instillation in fetal rabbits.
Instilling perfluorooctyl bromide (PFOB) into the fetal lung may lead to alveolar distension. The aim of the study was to evaluate the safety of PFOB instillation into fetal lungs and to determine the radiographic distribution and tissue concentration of PFOB in New Zealand white rabbits. Sibling fetuses of pregnant (day 27) New Zealand white rabbits were randomized to intratracheal instillation of 1 mL PFOB with tracheal ligation, instillation without ligation, and unmanipulated controls. The maternal animals were killed directly after instillation, at 3 or 6 hours (n = 10 each). For each study cohort, we determined fetal lung/body weight (FLBW) ratios, the radiographic distribution of PFOB, as well as pulmonary PFOB and water content by tissue distillation. PFOB concentrations in maternal and fetal tissues were assessed by gas chromatography. The relative amount of fetal lung PFOB recovered by fractional distillation was highest in ligated (25%) and lower in unligated lungs (9%). Extrapulmonary PFOB was found in the fetal brain (2.0 +/- 0.7 ppm), but not in any other fetal or maternal tissues. Mean FLBW ratios were highest in ligated fetuses, followed by unligated fetuses and controls. PFOB partially displaced fetal lung water. PFOB was visible in the lungs of all treated fetuses. Fetal survival between manipulated and unmanipulated fetuses did not differ. After prenatal intrapulmonary instillation, some PFOB remains in the lung, even if the trachea is not ligated, and may exert distending pressure on the alveoli.


Mechanisms for the effects of fish oil lipid emulsions in the management of parenteral nutrition-associated liver disease.
Parenteral nutrition (PN) can be life saving for infants unable to adequately absorb enteral nutrients due to intestinal failure from inadequate bowel length or function. However, long-term PN carries significant morbidity and mortality, with 30 to 60% of patients developing progressive liver dysfunction. The etiology of PN-associated liver disease (PNALD) is poorly understood, however the involvement of lipid emulsions in its pathogenesis has been clearly established, with new emphasis emerging on the role of omega-6 polyunsaturated fatty acids and omega-3 polyunsaturated fatty acids. Recent studies evaluating the use of parenteral fish oil lipid emulsions instead of soybean oil lipid emulsions have demonstrated marked improvements in cholestasis, morbidity, and mortality in patients with PNALD treated with fish oil. This review provides an overview of the role of lipid emulsions in the pathogenesis of PNALD and the proposed mechanisms by which parenteral fish oil lipid emulsions may be exerting their beneficial effects.


Phylogenetic analyses of typical bovine rotavirus genotypes G6, G10, P[5] and P[11] circulating in Argentinean beef and dairy herds.
Group A rotavirus (RVA) is one of the main causes of neonatal calf diarrhea worldwide. RVA strains affecting Argentinean cattle mainly possess combinations of the G6, G10, P[5] and P[11] genotypes. To determine RVA diversity among Argentinean cattle, representative bovine RVA strains detected in diarrheic calves were selected from a survey conducted during 1997-2009. The survey covered the main livestock regions of the country from dairy and beef herds. Different phylogenetic approaches were used to investigate the genetic evolution of RVA strains belonging to the prevalent genotypes. The nucleotide phylogenetic tree showed that all genotypes studied could be divided into several lineages. Argentinean bovine RVA strains were distributed across multiple lineages and most of them were distinct from the lineage containing the vaccine strains. Only the aminoacid phylogenetic tree of G6 RVA strains maintained the same lineages as observed at the nucleotide level, whereas a different clustering pattern was observed for the aminoacid phylogenetic trees of G10, P[5] and P[11] suggesting that the strains are more closely related at the aminoacid level than G6 strains. Association between P[5] and G6(IV), prevalent in beef herd, and between P[11] and G6(III) or G10 (VI and V), prevalent in dairy herds, were found. In addition, Argentinean G6(III), G10, P[5] and P[11] bovine RVA strains grouped together with human strains, highlighting their potential for zoonotic transmission. Phylogenetic studies of RVA circulating in animals raised for consumption and in close contact with humans, such as cattle, contribute to a better understanding of the epidemiology of the RVA infection and evolution.


A Novel Ultrasound Robot with Force/torque Measurement and Control for Safe and Efficient Scanning.
Medical ultrasound is of increasing importance in medical diagnosis and intraoperative assistance and possesses great potential advantages when integrated with robotics. However, some concerns, including the operation efficiency, operation safety, image quality, and comfort of patients, remain after introducing robotics into medical ultrasound. In this paper, an ultrasound robot integrating a force control mechanism, force/torque measurement mechanism, and online adjustment method, is proposed to overcome the current limitations. The ultrasound robot can measure operating forces and torques, provide adjustable constant operating forces, eliminate great operating forces introduced by accidental operations, and achieve various scanning depths based on clinical requirements. The proposed ultrasound robot would potentially facilitate sonographers to find the targets quickly, improve operation safety and efficiency, and decrease patients' discomfort. Simulations and experiments were carried out to evaluate the performance of the ultrasound robot. Experimental results show that the proposed ultrasound robot is able to detect operating force in the z-direction and torques around the x- and y- directions with errors of 3.53% F.S., 6.68% F.S., and 6.11% F.S., respectively, maintain the constant operating force with errors of less than 0.57N, and achieve various scanning depths for target searching and imaging. This proposed ultrasound robot has good performance and would potentially be used in medical ultrasound.


Functional Symmetry Observation Scale, Version 2: Development and Content Validation Using a Modified Delphi Method.
To describe the development of the Functional Symmetry Observation Scale (FSOS) Version 2 and its content validation. The FSOS Version 2 is an observational assessment that quantifies symmetry in spontaneous movement and posture in infants with congenital muscular torticollis, age birth to 18 months. Twenty expert pediatric physical therapists were identified through purposive sampling and invited to participate in a modified Delphi study. Survey data were collected on Qualtrics. Consensus was evaluated using median ratings and percent agreement on Likert Scale items. Thematic analysis was performed for open-ended question responses. Thirteen experts completed Round 1 and 2 surveys. In Round 1, consensus was achieved on all but 1 item. The scale was modified based on received feedback. In Round 2, consensus was achieved on all items (median rating of 4, agreement at 85%-100%). This study established the content validity of the FSOS Version 2.