Retinal Vasculitis Associated With Dermatomyositis Treated With Intravenous Steroids.
This work aims to present treatment and long-term follow-up of a 31-year-old woman with dermatomyositis who presented with hemorrhagic retinal vasculitis and macular edema. A retrospective case report is presented. A 31-year-old woman with dermatomyositis treated with systemic immunosuppression was evaluated for acute, reduced vision. Best-corrected visual acuity was hand motion in the right eye and 20/200 in the left eye. Fundus examination revealed diffuse intraretinal hemorrhages, cotton-wool spots, and vascular sheathing with a frosted branch angiitis-like appearance. Optical coherence tomography revealed significant macular edema and subretinal fluid that quickly resolved after admission and treatment with intravenous steroids. Multimodal imaging at 7-year follow-up disclosed long-term sequelae including peripheral nonperfusion and retinal neovascularization. When vasculitis associated with dermatomyositis is treated aggressively with intravenous steroids at initial presentation, good visual acuity outcomes can be achieved, but long-term consequences of retinal nonperfusion and neovascularization persist.


Screening of obstructive sleep apnea syndrome by the deep breathing technique.
Obstructive sleep apnea syndrome (OSAS) is associated with alterations in heart rate variability (HRV) in relation to chronic autonomic dysfunction. We tested the ability of the deep breathing technique-a simple way to evaluate HRV-to identify patients with OSAS. Consecutive patients referred for suspected OSAS (without obesity, diabetes, and heart diseases) were included. They underwent a measure of HRV at rest and of heart rate oscillations during expiration vs inspiration (DeltaHRDB) when breathing deeply at the resonant frequency of 6 cycles per minute (deep breathing technique) while sitting awake, followed by a nighttime polysomnography. We measured DeltaHRDB and performed temporal and spectral HRV analysis. Of 31 included participants (77% male), 14 had mild to moderate OSAS (apnea-hypopnea index median [IQR]: 18 [12]) and 17 had no OSAS. The conventional HRV analysis did not reveal any difference between the groups with vs without OSAS. However, the DeltaHRDB was lower in those with than without OSAS. Lower DeltaHRDB correlated with higher apnea-hypopnea index, arousal index, and desaturation degree. A DeltaHRDB below 11 beats per minute (bpm) predicted OSAS with a sensitivity of 100% and specificity of 86%. The deep breathing technique accurately identifies a reduction in cardiac changes in patients with mild to moderate OSAS. It could be used as a simple screening tool to select patients for polysomnography. Onanga M, Joanny S, Rivals I, et al. Screening of obstructive sleep apnea syndrome by the deep breathing technique. J Clin Sleep Med. 2023;19(2):293-302.


A systematic review of interventions by healthcare professionals on community-dwelling postmenopausal women with osteoporosis.
A systematic review was conducted to evaluate evidence concerning the effect of non-drug interventions by healthcare professionals on community-dwelling postmenopausal osteoporotic women. Evidence available indicates that such interventions are effective in improving the quality of life, medication compliance, and calcium intake, but effect on other outcomes is less conclusive. The purpose of this study is to conduct a systematic review to evaluate evidence concerning the effect of non-drug interventions by healthcare professionals on community-dwelling postmenopausal osteoporotic women. Randomized controlled trials (RCTs) published in English between year 1990 and 2009 were identified. Types of patient outcome used as assessment included quality of life (QOL), bone mineral density (BMD), medication compliance and persistence, knowledge level, and lifestyle modification. Twenty four RCTs met the inclusion criteria. Seven studies assessed interventions by physiotherapists, six by physicians, seven by nurses, three by multi-disciplinary teams and one by dietitians. Variability in the types and intensity of interventions made comparison between each study difficult. Collectively, these studies provided some evidence to show that interventions by healthcare professionals improved the QOL medication compliance and calcium intake of patients but its effects on BMD, medication persistence, knowledge, and other lifestyle modifications were less conclusive. From this review, it was found that some outcome measures of such non-drug interventions still required further studies. Future studies should use validated instruments to assess the outcomes, with focus on common definitions of interventions and outcome measures, more intensive one-to-one interventions, appropriate control groups, adequate randomization procedures, and also provide information on effect size.


How CrRLK1L Receptor Complexes Perceive RALF Signals.
RALFs are secreted peptides that are perceived by various CrRLK1L-LRE/LLG receptor complexes. The mechanistic basis of this perception has now been elucidated showing that the co-receptor LLG binds RALF23 to nucleate a FER receptor complex. This interaction likely occurs in other tissues where RALFs meet CrRLK1L receptors and LRE/LLG co-receptors.


What should be done to combat misinformation about health products?
The increasing role of digital technology, social media, the wide range of channels and the volume of information, the role of medicine as a societal subject, public information that is insufficient and poorly suited to situations of uncertainty are all observations which led to the theme of this round table. After discussing the definition of disinformation, which is not limited to fake news, and talking about contributors who misinform, whether intentionally or not, the participants of this round table made nine recommendations (R) to combat disinformation about health products: create a collaborative platform, information/training on health products, a platform with five major characteristics, namely accessibility, flexibility, objectivity, transparency and independence, as well as media suited to the different targets (R1); promote basic knowledge on health products: education/training to restore the particularly poor image of medication, and teach the public how to use basic concepts appropriately (R2); improve communication to the public based on the observation that information is the main weapon against misinformation and entails, in particular, coordinating communication from the different institutions to make public information more audible, making institutional messages clearer, ensuring they are more factual and prioritising them (R3); know how to communicate using the correct codes and tools (R4), because, to be understood, the substance and the form are inseparable; develop research on communication in the field of health products (R5); acquire tools to identify and regulate as soon as possible (R6); keep check of content by developing critical thinking (R7); define quality criteria for information sources (R8); identify, assess and reference initiatives for the public that could be placed on the platform (R9).


Electromagnetic acupuncture to enhance the effects of manual acupuncture on recovery from muscle fatigue of the quadriceps.
The aim of this study was to investigate a new method of manual acupuncture that used a magnetic field to stimulate only one acupoint vertically. We developed an eight-channel electromagnetic acupuncture (EMA) system that uses a solenoid-type electrode to insert the manual acupuncture needle into a hole in an electrode. We used a manual acupuncture needle for magnetic induction in order to penetrate vertically and deeply into tissues. In order to confirm the usefulness of EMA, we investigated the effects of treatment on muscle fatigue after strenuous knee extension/flexion exercises that had been performed by three groups: the nonstimulation, the manual acupuncture, and the EMA groups. Electromyograms showed that the median frequency (MF) in the EMA group had rapidly recovered after 4 minutes (p = 0.608), but that the peak torque had not recovered to the normal state (p < 0.05). Thus, we confirmed that compared with manual acupuncture, EMA resulted in better recovery from muscle fatigue.


Speech therapy in Brazil: forty years of existence, two decades of recognition.
The history of speech therapy in Brazil is presented, outlining the creation of the first course, the courses of Master's degree and the current situation, along with the main responsible aspects for it.


Rapid cervicovaginal smear screening: method of quality control and assessing individual cytotechnologist performance.
To validate the method of rapid screening (RS) in the detection of cervical lesions and false-negative results as well as in quality control of cytotechnologist performance. The RS method was validated on Papanicolaou-stained and initially conventionally analysed vaginal, cervical and endocervical (VCE) smears collected in an opportunistic programme for the detection of cervical carcinoma. The study included 3680 VCE smears from the Department of Gynaecologic Cytology, University Department of Gynaecology and Obstetrics, Zagreb University Hospital Center, Zagreb and from the Department of Clinical Cytology, Osijek University Hospital, Osijek. Histologically verified abnormal findings accounted for 10% of the study samples. Thirteen cytotechnologists, with no previous experience in RS, performed the test. Each slide was examined using the 'step' technique for 1.5 minutes, the findings were classified as negative or abnormal, and the abnormal ones were also classified according to differential cytological diagnosis. The results were compared with those obtained on initial screening. Abnormal findings from a group of initially negative findings were reanalysed using conventional methods to make definitive cytological diagnosis. RS yielded a sensitivity of 83.7%, specificity of 93.7%, positive predictive value of 62.4%, negative predictive value of 97.9% and diagnostic accuracy of 92.6%. Relative to the initial abnormal differential cytological diagnosis, the diagnostic value of RS increased with lesion severity [54.8%, 68.0% and 91.3% for cervical intraepithelial neoplasia (CIN) I, CIN II and CIN III respectively]. RS detected 38 additional positive findings; 94.2% of these were atypical squamous cells of undetermined significance (ASCUS)/abnormal glandular cells undetermined significance (AGUS) and CIN I. The rate of additional positive findings was 1.14% (38/3135). The false-negative rate of initial screening was 9.4% (38/406), and individual cytotechnologist sensitivity was 60.0-100.0%. RS could be introduced as an efficient method of quality control to improve the sensitivity of cytological screening as well as for quality control of cytotechnologist performance.


Corynoline protects against zearalenone-induced liver injury by activating the SIRT1/Nrf2 signaling pathway.
Corynoline has been reported to have anti-inflammatory and antioxidative effects. In the present study, the potential protective effects of corynoline against zearalenone (ZEA)-induced liver injury were investigated. ZEA was administered daily for 5 days. Then, liver tissues were used for subsequent experiments. Corynoline attenuated liver histopathological changes induced by ZEA. The production of tumor necrosis factor-α and interleukin-1β in liver tissues, as well as aspartate aminotransferase and alanine aminotransferase in serum, was also inhibited by corynoline. Meanwhile, ZEA-induced MPO activity and MDA content were both attenuated by corynoline. ZEA-induced NF-κB p65 and IκBα phosphorylation were inhibited by corynoline. Furthermore, SIRT1, Nrf2, and HO-1 expression were increased by corynoline. In addition, the protective effects of corynoline against liver injury were reversed by the SIRT1 inhibitor EX-527. Taken together, corynoline protected against ZEA-induced liver injury by activating the SIRT1/Nrf2 signaling pathway.


Promoting scholarship in improvement science: A model for academic clinical departments.
Clinical departments at academic medical centers strive to deliver clinical care, provide education and training, support faculty development, and promote scholarship. These departments have experienced increasing demands to improve the quality, safety, and value of care delivery. However, many academic departments lack a sufficient number of clinical faculty members with expertise in improvement science to lead initiatives, teach, and generate scholarship. In this article, we describe the structure, activities, and early outcomes of a program within an academic department of medicine to promote scholarly improvement work. The Department of Medicine at the University of Vermont Medical Center launched a Quality Program with three primary goals: (a) improve care delivery, (b) provide education and training, and (c) promote scholarship in improvement science. The program serves as a resource center for students, trainees and faculty, offering education and training, analytic support, consultation in design and methodology, and project management. It strives to integrate education, research, and care delivery to learn, apply evidence and improve health care. Over the first 3 years of full implementation, the Quality Program supported an average of 123 projects annually, including prospective clinical quality improvement initiatives, retrospective assessment of clinical programs and practices, and curriculum development and evaluation. The projects have yielded a total of 127 scholarly products, defined as peer-reviewed publications and abstracts, posters, and oral presentations at local, regional, and national conferences. The Quality Program may serve as a practical model for promoting care delivery improvement, training, and scholarship in improvement science while advancing the goals of a learning health system at the level of an academic clinical department. Dedicated resources within such departments offer the potential to enhance care delivery while promoting academic success for faculty and trainees in improvement science.


Gene cloning, prokaryotic expression and antiviral activities of interferon-αω from Chinese Bama miniature pigs.
Porcine interferon (PoIFN) complex represents an ideal model for studying IFN evolution that resulted from viral pressure during domestication. IFN-αω is an emergent subtype of type I IFNs which has been primarily characterized in domestic pigs. In this study, the PoIFN-αω cDNA was cloned from Chinese Bama miniature pigs by RT-PCR, and its tissue expression profile was analyzed by real-time RT-PCR. The cDNA was expressed in Escherichia coli as a His-tagged protein and purified by nickel affinity chromatography. The antiviral activities of recombinant PoIFN-αω (rPoIFN-αω) against four different pig viruses were measured using cytopathic effect (CPE) inhibition assay. Although the PoIFN-αω sequence of Bama miniature pigs was identical to that of domestic pigs, the tissue expression profiles differed significantly between the two pig species. The rPoIFN-αω showed dose-dependent pre-infection antiviral activities against porcine pseudorabies virus, vesicular stomatitis virus and porcine reproductive and respiratory syndrome virus, but not against porcine circovirus type 2. When used as treatment post infection with the three viruses, rPoIFN-αω showed the efficacy in decreasing CPE in the infected cells in a time-dependent manner. Therefore, the expressed rPoIFN-αω could be used as an antiviral agent against pig virus infections.


Prediction of disease progression in patients with COVID-19 by artificial intelligence assisted lesion quantification.
To investigate the value of artificial intelligence (AI) assisted quantification on initial chest CT for prediction of disease progression and clinical outcome in patients with coronavirus disease 2019 (COVID-19). Patients with confirmed COVID-19 infection and initially of non-severe type were retrospectively included. The initial CT scan on admission was used for imaging analysis. The presence of ground glass opacity (GGO), consolidation and other findings were visually evaluated. CT severity score was calculated according to the extent of lesion involvement. In addition, AI based quantification of GGO and consolidation volume were also performed. 123 patients (mean age: 64.43 ± 14.02; 62 males) were included. GGO + consolidation was more frequently revealed in progress-to-severe group whereas pure GGO was more likely to be found in non-severe group. Compared to non-severe group, patients in progress-to-severe group had larger GGO volume (167.33 ± 167.88 cm3 versus 101.12 ± 127 cm3, p = 0.013) as well as consolidation volume (40.85 ± 60.4 cm3 versus 6.63 ± 14.91 cm3, p < 0.001). Among imaging parameters, consolidation volume had the largest area under curve (AUC) in discriminating non-severe from progress-to-severe group (AUC = 0.796, p < 0.001) and patients with or without critical events (AUC = 0.754, p < 0.001). According to multivariate regression, consolidation volume and age were two strongest predictors for disease progression (hazard ratio: 1.053 and 1.071, p: 0.006 and 0.008) whereas age and diabetes were predictors for unfavorable outcome. Consolidation volume quantified on initial chest CT was the strongest predictor for disease severity progression and larger consolidation volume was associated with unfavorable clinical outcome.


The effects of standing tutorial meetings on physical activity behavior in undergraduates: A randomized controlled trial.
This study explored the effects of using standing desks in tutorial meetings on the physical activity behavior (PAB) of undergraduate students. Standing desks have been introduced to minimize the detrimental health effects of prolonged sedentary behavior (SB). The effectiveness of using standing desks has not been explored among undergraduate students - a population showing high SB. Ninety-six undergraduate students were randomly assigned to a sitting or standing tutorial group that ran for nine weeks, and their PAB was monitored using the activPAL3™ triaxial activity monitor. To check for potential compensatory or other covarying behaviors, the students' PAB was monitored on tutorial and non-tutorial days. PAB monitoring was conducted in week 4-5, and a follow-up measurement was conducted in week 9 to examine longer-term effects. In week 4-5, the stand group (n = 41) showed less SB (β = -0.092, SE = 0.044, 95% CI: -0.179, -0.006) and more moderate-to-vigorous physical activity (β = 0.320, SE = 0.160, 95% CI: 0.004, 0.635) compared to the sit group (n = 36). On tutorial days, the stand group showed more light physical activity (LPA) than the sit group (p < .001, d = 1.04). In week 9, there was an exam on the last day of that week. Nonetheless, the stand group (n = 37) showed less SB (p < .001, d = 0.378) and more LPA (p = .008, d = 0.725), while breaking up prolonged SB more frequently (p = .007, d = 0.696) on the tutorial day compared to the sit group (n = 32). Overall, undergraduates attending standing tutorial meetings showed less SB and more LPA than those attending conventional, seated tutorial meetings. Standing tutorial meetings can contribute to a more active lifestyle for undergraduates.


Efficacy and safety of sotagliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease.
To assess the efficacy and safety of sotagliflozin, a dual inhibitor of sodium-glucose co-transporters 1 and 2, in adults with type 2 diabetes (T2D) and stage 3 chronic kidney disease (CKD3). This phase 3, randomized, placebo-controlled trial evaluated sotagliflozin 200 and 400 mg in 787 patients with T2D and an estimated glomerular filtration rate of 30-59 ml/min/1.73m2 . The primary objective was superiority of week 26 HbA1c reductions with sotagliflozin versus placebo. Secondary endpoints included changes in other glycaemic and renal endpoints overall and in CKD3 subgroups. At 26 weeks, the placebo-adjusted mean change in HbA1c (from a baseline of 8.3% ± 1.0%) was -0.1% (95% CI: -0.2% to 0.05%; P = .2095) and -0.2% (-0.4% to -0.09%; P = .0021) in the sotagliflozin 200 and 400 mg groups, respectively. Significant reductions in fasting plasma glucose and body weight, but not systolic blood pressure, were observed. Among patients with at least A2 albuminuria at week 26, the urine albumin-creatinine ratio (UACR) was reduced with both sotagliflozin doses relative to placebo. At week 52, UACR was reduced with sotagliflozin 200 mg in the CKD3B group. Adverse events (AEs), including serious AEs, were similar between the treatment groups. After 26 weeks, HbA1c was significantly reduced with sotagliflozin 400 but not 200 mg compared with placebo in this CKD3 cohort. UACR in patients with at least A2 albuminuria was reduced with each of the two doses at 26 weeks, but changes were not sustained at week 52. The safety findings were consistent with previous reports (NCT03242252).


Effect of growth temperature on ether lipid biochemistry in Archaeoglobus fulgidus.
The archaea are distinguished by their unique isoprenoid ether lipids, which typically consist of the sn-2,3-diphytanylglycerol diether or sn-2,3-dibiphytanyldiglycerol tetraether core modified with a variety of polar headgroups. However, many hyperthermophilic archaea also synthesize tetraether lipids with up to four pentacyclic rings per 40-carbon chain, presumably to improve membrane thermal stability at temperatures up to approximately 110 degrees C. This study aimed to correlate the ratio of tetraether to diether core lipid, as well as the presence of pentacyclic groups in tetraether lipids, with growth temperature for the hyperthermophilic archaeon, Archaeoglobus fulgidus. Analysis of the membrane core lipids of A. fulgidus using APCI-MS analysis revealed that the tetraether-to-diether lipid ratio increases from 0.3 +/- 0.1 for cultures grown at 70 degrees C to 0.9 +/- 0.1 for cultures grown at 89 degrees C. Thin-layer chromatography (TLC) followed by APCI-MS analysis provided evidence for no more than one pentacycle in the hydrocarbon chains of tetraether lipid from cultures grown at 70 degrees C and up to 2 pentacycles in the tetraether lipid from cultures grown at higher temperatures. Analysis of the polar lipid extract using TLC and negative-ion ESI-MS suggested the presence of diether and tetraether phospholipids with inositol, glycosyl, and ethanolamine headgroup chemistry.


Cardiomyoplasty as an isolated procedure to treat refractory heart failure.
Cardiomyoplasty represents a controversial therapy for chronic heart failure. The aim of this study is to review our experience of such a surgical procedure as an isolate approach to treat refractory left ventricular dysfunction. Twenty-two patients were considered candidates for cardiomyoplasty because of chronic heart failure. Mean age was 58.7 +/- 5.3 (range 48-71 years), 19 patients were male and 3 were female. Ischemic or idiopathic etiology was present in 11 cases, respectively. Traditional as well as innovative techniques were used to assess hemodynamic function. Pre-operative hemodynamic profile included mean left ventricular ejection fraction of 20 +/- 5.8% (9-28%), absence of severe right ventricular failure, and mean left ventricular end-diastolic diameter of 75.5 +/- 7.4 mm (range 61-92 m). All patients were in New York Heart Association Class III or Intermittent IV despite conventional medical therapy. There was no intra-operative death. No additional surgery was performed. Left latissimus dorsi (LD) muscle was used in 20 cases, and right LD in two patients. Early mortality occurred in one patient (low cardiac output syndrome), whereas late mortality in five patients (three sudden deaths, one lung cancer, one heart failure). Mean follow-up is 20.7 +/- 16.7 months (3-51 months). Actuarial survival at 4 years is 70%. Cardiac index increased at 6 months (3.08 +/- 0.5 l/min per m2, P = 0.04), but no other significant changes were observed in the long term (3.03 +/- 0.7 l/min per m2, 3 +/- 0.7 l/min per m2, and 2.85 +/- 0.7 l/min per m2, at 12, 24 and 36 months, respectively). Ejection fraction improved at 6 and 12 months (29.1 +/- 1.03%, P = 0.0017; and 27.3 +/- 5.6%, P = 0.0091, respectively), while no substantial augmentation was documented at 2 and 3 years (25.6 +/- 2.5% and 25.1 +/- 4.0%, respectively). Left ventricular end-diastolic diameter was markedly reduced at 6 (73.2 +/- 8.0 mm, P = 0.0176), 12 (69.4 +/- 8.5 mm, P = 0.002) and 24 months (71.1 +/- 7.0 mm, P = 0.011), and was then stable (74.0 +/- 9.1 mm, P = 0.47) at 36 months. Postoperative pressure/volume loop evaluation showed some improvement of hemodynamic function from skeletal muscle assistance. Acute pulmonary edema episodes, as well as number of hospitalizations, were considerably reduced following cardiomyoplasty. In our experience, cardiomyoplasty was shown to exert moderate beneficial influence on left ventricular performance, to significantly reduce cardiac dilatation and to promote the stabilization of the disease course.


Staff model HMO's and managed mental health care: one plan's experience.
HMO staff model mental health programs have particular expertise in providing these services in an integrated fashion within the context of a total medical care system. "Carve-out" approaches to managed mental health care risk losing the added value found in primary care based integrated mental health services. Employers as purchasers of care are seeking demonstrated value in services, and the rise of specialty mental health managed care firms is bringing the efficiencies of managed mental health care familiar to HMO's to a broader audience. Faced with employer concerns, and this new competitive environment, many HMO's are examining their mental health services to determine how these services may respond to the needs being expressed by employers today for new program options. The Community Health Plan's (CHP) experience is presented to illustrates one approach HMO's are taking in today's competitive health care environment.


Safety and antigenicity of influenza A/Hong Kong/68-ts-1 (E) (H3N2).
Influenza A/Hong Kong/68-ts-1 [E] (H3N2) vaccine was administered intranasally to 18 seronegative children 14 to 32 months of age. Fourteen children, 78%, shed influenza A/Hong Kong virus for a mean of eight days following vaccination. Sixteen children, 89%, experienced a fourfold or greater rise in hemagglutination-inhibition antibody. Some children appeared to experience a febrile reaction to the vaccine although interpretation of this data was complicated by intercurrent illness. These findings demonstrate that influenza A ts-1 [E] replicates more readily in the young seronegative child than in the HAI negative adult. In addition, the temperature-sensitive marker of the vaccine was not genetically stable in four of the vaccinated children. Careful evaluation of any future live respiratory viral vaccines needs to be undertaken in the young seronegative child before the vaccine's safety is fully established.


Identification of candidate genes important for frost tolerance in Festuca pratensis Huds. by transcriptional profiling.
Studies of differential gene expression between cold acclimated (CA) and non-cold acclimated (NA) plants yield insight into how plants prepare for cold stress at the transcriptional level. Furthermore genes involved in the cold acclimation process are good candidate loci for genetic variation in frost tolerance and winter survival. In this study we combine different approaches to try to decode the genetics of cold acclimation and frost tolerance in meadow fescue (Festuca pratensis Huds). An EST library of cold acclimation responsive genes was established by suppression subtractive hybridization (SSH), and a microarray experiment was used to identify gene expression differences between high and low frost tolerance genotypes in response to cold acclimation. Many genes known to be involved in CA in other species were confirmed to be involved in CA in F. pratensis, however, 18% of the ESTs did not show significant homology to any database proteins. Seven genes were found to be differentially expressed (>2-fold) between high and low frost tolerance genotypes. Two of these genes, FpQM and FpTPT, represent interesting candidate genes for frost tolerance in perennial forage grasses.


Inhibition mechanism of hydroxypropyl methylcellulose acetate succinate on drug crystallization in gastrointestinal fluid and drug permeability from a supersaturated solution.
The effects of drug-crystallization inhibitor in bile acid/lipid micelles solution on drug permeation was evaluated during the drug crystallization process. Hydroxypropyl methylcellulose acetate succinate (HPMC-AS) was used as a drug-crystallization inhibitor, which efficiently suppressed dexamethasone (DEX) crystallization in a gastrointestinal fluid model containing sodium taurocholate (NaTC) and egg-phosphatidylcholine (egg-PC). Changes of molecular state of supersaturated DEX during the DEX crystallization process was monitored in real time using proton nuclear magnetic resonance (1H NMR). It revealed that DEX distribution to bulk water and micellar phases formed by NaTC and egg-PC was not changed during the DEX crystallization process even in the presence of HPMC-AS. DEX permeation during DEX crystallization was evaluated using dissolution/permeability system. The combination of crystallization inhibition by HPMC-AS and micellar encapsulation by NaTC and egg-PC led to considerably higher DEX concentrations and improvement of DEX permeation at the beginning of the DEX crystallization process. Crystallization inhibition by HPMC-AS can efficiently work even in the micellar solution, where NaTC/egg-PC micelles encapsulates some DEX. It was concluded that a crystallization inhibitor contributed to improvement of permeation of a poorly water-soluble drug in gastrointestinal fluid.


Sensitivity of the McGill Pain Questionnaire to intensity and quality of laboratory pain.
Subjects completed a modified McGill Pain Questionnaire (MPQ) to describe one of two laboratory stressors (cold pressor or electrical tooth pulp stimulation) at one of two subjective intensities (pain threshold or pain tolerance). Differences in MPQ-derived scores were associated with both type of stressor and intensity level, as were patterns of frequently chosen word groups and specific words. These data support the validity of interpretations drawn from MPQ differences in clinical practice and research. In addition, the fact that the MPQ can be used in both clinical and laboratory settings suggests one way in which relevant dimensions of similarity and difference among "types" of pain may be clarified in later research.


Stimulation of glucose transport in skeletal muscle by the sodium ionophore monensin.
The tissue/medium distribution of the nonmetabolized glucose analog 3-O-methyl-D-glucose was measured in mouse diaphragm muscle and related to changes in 45Ca influx, Na+ content and Na+-pump activity. In the presence of external Ca2+ the sodium ionophore monensin greatly increased cellular Na+ content (and decreased K+ content) although 86Rb uptake, reflecting Na+-pump activity was increased. Concomitantly, 45Ca influx was stimulated, presumably through activation of Na+-Ca2+ exchange. In parallel to the rise in Ca2+ influx sugar transport was also increased. Sugar transport was also increased by monensin in the nominal absence of external Ca2+, when Ca2+ influx was minimal. To test if monensin releases Ca2+ from intracellular storage sites in the absence of external Ca2+, the ionophore was added to medium perfusing rat hind limb preparations and the total Ca content of muscle mitochondria was determined. When Ca2+ was present in the perfusate, monensin increased the mitochondrial Ca content. In the absence of Ca2+, the mitochondrial Ca content was lower and was further depressed by monensin, suggesting that elevation of internal Na+ by monensin may increase mitochondrial Ca2+ loss via activation of Na+-Ca2+ exchange across the mitochondrial membrane. The above results are consistent with the effect of monensin on sugar transport being due to alterations in Ca2+ distribution. They support the earlier conclusion that regulation of sugar transport in muscle is Ca2+ dependent.


Detection of populations of amyloid-like protofibrils with different physical properties.
We used tapping mode atomic force microscopy to study the morphology of the amyloid protofibrils formed at fixed conditions (low pH with high ionic strength) by self-assembly of the N-terminal domain of the hydrogenase maturation factor HypF. Although all protofibrils in the sample share a beaded structure and similar values of height and width, an accurate analysis of contour length and end-to-end distance and the comparison of experimental data with theoretical predictions based on the worm-like chain model show that two different populations of protofibrils are present. These populations are characterized by different physical properties, such as persistence length, bending rigidity and Young's modulus. Fluorescence quenching measurements on earlier globular intermediates provide an independent evidence of the existence of different populations. The finding that differences in mechanical properties exist even within the same sample of protofibrils indicates the presence of different subpopulations of prefibrillar aggregates with potentially diverse tendencies to react with undesired molecular targets. This study describes a strategy to discriminate between such different subpopulations that are otherwise difficult to identify with conventional analyses.


Prevalence of hypothalamic-pituitary imaging abnormalities in impotent men with secondary hypogonadism.
Because prevalence of structural lesions of the pituitary and hypothalamus in impotent men with secondary hypogonadism was undefined, we evaluated 164 men 27 to 79 years old whose chief complaint was erectile dysfunction and who repeatedly had low serum testosterone levels (less than 230 ng./dl.). With computerized tomography or magnetic resonance imaging of the sella we detected potentially serious lesions (pituitary lesions greater than 5 mm. or any hypothalamic lesion) in 11 men (6.7%, 95% confidence interval 2.9 to 10.5%), including 5 pituitary microadenomas (5 mm. or larger), 4 pituitary macroadenomas and 2 hypothalamic lesions. Mean serum testosterone was lower in patients with (121 +/- 66 ng./dl., standard deviation) than without (177 +/- 39 ng./dl.) hypothalamic or pituitary imaging abnormalities (p < 0.001). For every 10 ng./dl. decrease in testosterone the risk of hypothalamic or pituitary imaging abnormalities increased 1.2-fold (p < 0.005). Macroadenomas and hypothalamic lesions were confined to 6 subjects with testosterone levels of 104 ng./dl. or less. The risk of hypothalamic or pituitary imaging abnormalities is low among men evaluated for erectile dysfunction and secondary hypogonadism. However, this risk increases markedly when the serum testosterone level is markedly decreased.


Congenital muscular dystrophy (CMD) - a collagen formative disease?
Muscle biopsies of 5 patients with congenital muscular dystrophy (CMD) (8 months to 3 years old) were examined by electron microscopy to determine ultrastructural abnormalities of the muscle as well as of the connective tissue cells. Two populations of muscle fibers were observed in each biopsy. Besides muscle fibers with normal or enlarged diameters there were frequently very small muscle cells indicating immaturity. The most interesting findings in each biopsy were myofibroblast-like cells exhibiting active protein synthesis. Large amounts of collagen fibrils with abnormal diameters as well as accumulation of elastic fibrils within the endomysium in CMD suggest abnormalities in collagen synthesis.


On the structure of the prosthetic group of citrate (pro-3S)-lyase.
The prosthetic group of citrate (pro-3S)-lyase from Klebsiella aerogenes as well as Streptococcus diacetilactis was obtained eigher by beta elimination or pronase digestion of the enzyme and purified by DEAE-cellulose chromatography. The compound was shown to contain 3 mol of PO4, 2 mol of ribose, and 1 mol of sulfhydryl/mol of adenine. 5'-AMP and dephospho-CoA are components of the prosthetic group. The evidence obtained so far support our proposed structure of 3' (or 2') leads to 1''-(5''-phosphoribosyl)dephospho-CoA for the prosthetic group of citrate lyase. The presence of one phosphomonoester group in the compound isolated after beta elimination and the absence of the same in the compound isolated after pronase digestion indicated that the prosthetic group is attached to the enzyme through a phosphodiester bond. Analyses of the pyruvate released by beta elimination and subsequent acid hydrolysis of the peptide-bound prosthetic group and its degradation products showed that the phosphodiester linkage is between the hydroxyl group of a serine residue of the protein and the 5''-PO4 group of the second ribose.


Controlling Site-Directed RNA Editing by Chemically Induced Dimerization.
Various RNA-targeting approaches have been engineered to modify specific sites on endogenous transcripts, breaking new ground for a variety of basic research tools and promising clinical applications in the future. Here, we combine site-directed adenosine-to-inosine RNA editing with chemically induced dimerization. Specifically, we achieve tight and dose-dependent control of the editing reaction with gibberellic acid, and obtain editing yields up to 20 % and 44 % in the endogenous STAT1 and GAPDH transcript in cell culture. Furthermore, the disease-relevant MECP2 R106Q mutation was repaired with editing yields up to 42 %. The introduced principle will enable new applications where temporal or spatiotemporal control of an RNA-targeting mechanism is desired.


A novel acetyl-CoA carboxylase inhibitor reduces de novo fatty acid synthesis in HepG2 cells and rat primary hepatocytes.
To identify the novel inhibitor of de novo lipogenesis in hepatocytes, we screened for inhibitory activity of triglyceride (TG) synthesis using [14C]acetate in the human hepatoma cell line, HepG2. Using this assay system we discovered the novel compound, benzofuranyl alpha-pyrone (TEI-B00422). TEI-B00422 also inhibited the incorporation of acetate into the triglyceride (TG) fraction in rat primary hepatocytes. In HepG2 cells, the incorporation of oleate into TG was unaffected. TEI-B00422 inhibited rat hepatic acetyl-CoA carboxylase (ACC), K(i)=3.3 microM, in a competitive manner with respect to acety-CoA but not fatty acid synthase and acyl-CoA transferase/diacylglycerol. Thus, these results suggest that the inhibition of TG synthesis by TEI-B00422 is based on the inhibitory action of ACC. The structure of TEI-B00422 is totally different from the known inhibitors of ACC and may be useful in the development of therapeutic agents to combat a number of metabolic disorders.


Inappropriate treatment of prostate cancer caused by heterophilic antibody interference.
A 58-year-old man, without any personal or familial risk factors for prostate cancer, visited his primary care physician for a first routine prostate cancer screening with a serum PSA test. Serum PSA test, digital rectal examination, prostate biopsy and pathological analysis, repeat serum PSA tests and pathological re-evaluation, abdominal tomodensitometry, whole-body bone scan and prostatic MRI. Highly elevated serum PSA indicative of advanced prostate cancer at high risk for metastasis. The patient was started on androgen deprivation therapy with goserelin acetate and bicalutamide. At 3 months, he was asymptomatic, his prostate was atrophic on digital rectal examination and he had suppressed serum testosterone. However, his serum PSA level remained highly elevated in the absence of any radiographic evidence of advanced cancer. A repeat PSA test using a different assay returned a negligible PSA concentration; evaluation with blocker agents revealed the presence of heterophilic antibody interference with the original PSA assay. The patient was rediagnosed as having a likely low-grade prostate adenocarcinoma; androgen deprivation therapy was stopped, and he was deemed a candidate for watchful waiting. At 15 months, his serum PSA level remained stable at a low level, and prostatic dynamic MRI showed no sign of tumor in the prostate or in the pelvis.


Prediction of future rheumatoid arthritis.
Rheumatoid arthritis (RA) results from an interaction between genetic susceptibility and environmental factors. Several of these factors are known, such as family history of RA, high birth weight, smoking, silica exposure, alcohol nonuse, obesity, diabetes mellitus, rheumatoid factor, anti-citrullinated protein antibody, and genetic variants such as the shared epitope and protein tyrosine phosphatase nonreceptor type 22. The impact of these factors can be modeled in the 2 main groups at risk of RA: family members of patients with RA and seropositive persons with or without arthralgia. Current models have the potential to select individuals for preventive strategies.


Integrated pancancer analysis reveals the oncogene characteristics and prognostic value of DIP2B in breast cancer.
Disco-interaction protein 2 homologue B (DIP2B) plays an important role in DNA methylation. There have been many reports on DIP2B in various diseases, but neither the diagnostic value nor the prognostic value of DIP2B across cancer types has been deeply explored. The expression levels of DIP2B in 33 cancer types were analysed based on data sets from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. The relationships of DIP2B expression with immune cell infiltration and immune-related gene expression were studied via the CIBERSORT, ESTIMATE and TISIDB tools. Gene set variation analysis (GSVA) was performed to identify pathways related to DIP2B. DIP2B knockdown by siRNA was performed in breast cancer cell lines to investigate the effect on proliferation, apoptosis and migration. The relationships of DIP2B expression with clinicopathological features and prognosis were analysed based on immunohistochemistry. DIP2B was highly expressed in 26 of 33 cancer types and was significantly associated with poor overall survival (OS) in breast invasive carcinoma (BRCA), mesothelioma and chromophobe renal cell carcinoma (each P < 0.05). DIP2B showed a negative correlation with the immune score, the infiltration levels of key immune killer cells (CD8 + T cells, activated NK cells and plasma cells), and the expression of major histocompatibility complex-related genes and chemokine-related genes in BRCA. Subtype analysis showed that DIP2B expression was associated with poor OS in Her-2 + BRCA patients (P < 0.05). DIP2B showed a negative correlation with immune killer cell infiltration and immune regulatory genes in BRCA subtypes. In BRCA, the GSVA results revealed that genes correlating positively with DIP2B were enriched in cancer-related pathways (PI3K-AKT) and cell-cycle-related pathways (MITOTIC_SPINDLE, G2M_CHECKPOINT and E2F_TARGETS), while genes correlating negatively with DIP2B were enriched in DNA_REPAIR. Knockdown of the DIP2B gene induced a reduction in proliferation and migration and an increase in apoptosis in breast cancer cell lines. DIP2B expression was associated with lymph node metastasis and poor histological grade in BRCA according to immunohistochemistry (each P < 0.05). DIP2B expression predicted reduced disease-free survival and OS in BRCA patients (each P < 0.05), especially those with the Her-2 + subtype (P = 0.023 and P = 0.069). DIP2B may be a prognostic biomarker for BRCA, especially for the Her-2 + subtype. DIP2B is associated with a "cold" tumour immune microenvironment in BRCA and might serve as a future target for immunotherapy.


TARPs and AMPA Receptors: Function Follows Form.
In this issue of Neuron, Ben-Yaacov et al. (2017) dissect the interaction between AMPA receptors and auxiliary (TARP) subunits, revealing essential roles for the receptor transmembrane and cytoplasmic domains, as well as for the TARP extracellular EX2 loop.


Development of glycolipids and gangliosides in lead treated neonatal rats.
Lead (0.01% or 0.1% in the diet) was given to rats from conception to an age of 14, 21 or 32 days, and the development of brain cerebrosides, sulfatides and gangliosides was followed. Animals which had received 0.1% lead displayed a marked retardation in the onset and a reduction in the final level (at 32 days) of the lipids characteristic for the myelination process (cerebrosides and sulfatides). A slight decrease was also seen in the level of gangliosides at 32 days. It is suggested that certain aspects of lead encephalopathy might be explained by the toxic effects of lead on the glia population and the consequent interference with normal formation of myelin.


Highly sensitive and extremely durable wearable e-textiles of graphene/carbon nanotube hybrid for cardiorespiratory monitoring.
Electroconductive textile yarns are of particular interest for their use as flexible and wearable sensors without compromising the properties and comfort of usual textiles. However, the detection of fine actions of the human body is quite challenging since it requires both the relatively higher sensitivity and stability of the sensor. Herein, highly sensitive, ultra-stable, and extremely durable piezoresistive wearable sensors were prepared by loading N-doped rGO and polydopamine-coated carbon nanotubes into silicon rubber tube. The wearable sensors thus produced show an excellent ability to sense subtle movement or stimuli with good sensitivity and repeatability. Furthermore, by bending the straight conductive silicon rubber tube (CSRT) into three different patterns, its sensitivity was then dramatically increased. Finally, the CSRT was found capable of sensing cardiorespiratory signals, indicating that the sensor would be an important step toward realizing bio-signal sensing for next-generation personalized health care applications.


Prospective effects of an artificial intelligence-based computer-aided detection system for prostate imaging on routine workflow and radiologists' outcomes.
Artificial intelligence (AI) is expected to alleviate the negative consequences of rising case numbers for radiologists. Currently, systematic evaluations of the impact of AI solutions in real-world radiological practice are missing. Our study addresses this gap by investigating the impact of the clinical implementation of an AI-based computer-aided detection system (CAD) for prostate MRI reading on clinicians' workflow, workflow throughput times, workload, and stress. CAD was newly implemented into radiology workflow and accompanied by a prospective pre-post study design. We assessed prostate MRI case readings using standardized work observations and questionnaires. The observation period was three months each in a single department. Workflow throughput times, PI-RADS score, CAD usage and radiologists' self-reported workload and stress were recorded. Linear mixed models were employed for effect identification. In data analyses, 91 observed case readings (pre: 50, post: 41) were included. Variation of routine workflow was observed following CAD implementation. A non-significant increase in overall workflow throughput time was associated with CAD implementation (mean 16.99 ± 6.21 vs 18.77 ± 9.69 min, p = .51), along with an increase in diagnostic reading time for high suspicion cases (mean 15.73 ± 4.99 vs 23.07 ± 8.75 min, p = .02). Changes in radiologists' self-reported workload or stress were not found. Implementation of an AI-based detection aid was associated with lower standardization and no effects over time on radiologists' workload or stress. Expectations of AI decreasing the workload of radiologists were not confirmed by our real-world study. German register for clinical trials https://drks.de/; DRKS00027391.


Strains of Lactobacillus spp. reduce chalkbrood in Apis mellifera.
Beekeeping activities have increased recently in Argentina, a country that is a major consumer of honey and other products from hives. With the advancement of monoculture areas in Argentina and worldwide, beekeepers move from one area to another in search of floral resources, thus spreading diseases such as chalkbrood, caused by the fungus Ascosphaera apis. Although there are few effective antifungals for the control of chalkbrood, different natural products have been investigated in recent years. Current research is focusing on the intestinal microbiota for the prevention of different pathogens and parasites. In this work, we analyzed the in vivo probiotic effect of three lactic acid bacteria (genus Lactobacillus spp.) isolated from pollen bread from apiaries of Jujuy province on A. apis strains from Spanish and Argentine provinces. Special hives were made for the assays, and a protective effect was observed in larvae of bees fed lactic acid bacteria added to sugar syrup at 105 CFU/mL concentrations, administered from May to September in two consecutive years. The results showed that the three lactic acid bacteria reduced larval mummification by percentages greater than 80%. Therefore, this work brings a first approximation of the in vivo probiotic effect of lactic bacteria against A. apis.


All-trans-retinoic acid restores CD4+ T cell response after sepsis by inhibiting the expansion and activation of myeloid-derived suppressor cells.
Patients are susceptible to immunosuppression in late-stage of sepsis, in which myeloid-derived suppressor cells (MDSCs) is an important contributor. This study aims to investigate whether all-trans-retinoic acid (ATRA), which has been proved to inhibit MDSCs generation in cancer, will ameliorate sepsis-induced immuno-suppression through modulating MDSCs. A clinically relevant "two-hit'' model of sepsis, the cecal ligation and puncture (CLP) model and secondary pneumonia model, were established in mice. The effects of ATRA on the mortality, the bacterial burden, the expansion and activity of CLP-induced MDSCs, as well as the function of CD4+ T cells were evaluated. In CLP model, ATRA was found to reduce frequency of MDSCs in spleen of mice and inhibit activity of MDSCs by regulating the generation and activity of arginase-1 and iNOS, and the secretion of immune-supressive cytokines. ATRA administration eventually reduced mortality of secondary infection by Legionella pneumophila in CLP-surviving mice, which might be associated with the restoration of CD4+ T cells proliferating and secreting activity. ATRA can restore CD4+ T cells dysfunction in sepsis by modulating the expansion and function of MDSCs and therefore provides a potential therapy that targets the immunosuppressive state of sepsis.


Genetic selection for high and low immune response in pigs: effects on immunoglobulin isotype expression.
Immunoglobulin (Ig) function varies by isotype and antibody activity is best mediated by isotypes most able to control the inciting infection. In pigs, a high ratio of IgG1:IgG2 is associated with resistance to disease caused by the extra-cellular bacterium Actinobacillus pleuropneumoniae. This ratio is controlled by type 1/type 2 cytokines in vitro, reflecting cell- (CMI) or antibody-mediated immune (AMI) responses, respectively. Animals were used which had been previously selectively bred for high (HIR) or low (LIR) combined AMI and CMI and had been immunized with hen eggwhite lysozyme (HEWL) in Quil A (days 0 and 14) while Bacillus Calmette Guérin was given on day 9. To test the hypothesis that lines do not differ in IgG isotype expression as antibody to HEWL, the ratio of anti-HEWL associated with IgG1 and IgG2 was determined at days 0, 9, 14 and 21. The ratio of IgG1:IgG2-associated antibody was always <1.0 indicating a type 1 response and differed significantly over time in HIR and LIR animals. After primary and secondary immunizations, the HIR animals' IgG1:IgG2-associated antibody ratio increased and approached 1 while for LIR animals the ratio decreased. Thus anti-HEWL antibody in HIR, but not LIR, approached balance in type 2:type 1 expression. Individual variation in immune response was frequently significant within each immune response group. Thus, proportional production of anti-HEWL antibody associated with IgG isotypes varies by individual and differs over time as a function of genotype in pigs selectively bred for HIR or LIR.


Self-harm behaviour, psychopathological distress and suicidal ideation in normal and deliberate self-harm outpatient's adults.
To identify the association among suicidal ideation, deliberate self-harm, and psychopathological distress in normal and deliberate self-harm adults. The cross-sectional study was conducted at the Department of Psychiatry, Military Hospital, Rawalpindi, Pakistan, from January to July 2017, and comprised deliberate self harm and normal adults aged 18-25 years. Psychiatric evaluation involved a semi-structured interview based on mental status examination. The self-harm tendency was assessed on the basis of self-harm inventory of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. Beck scale for suicide ideation and he depression anxiety and stress scale were also used for data collection. Data was analysed using SPSS 22. There were 200 subjects with a mean age of 20.89±9.06 years; 100(50%) each in deliberate self-harm and normal groups. Deliberate self-harm was significantly positively associated with suicidal ideation and mental health problems, including depression, anxiety and stress (p<0.05). Deliberate self-harm tendency was also positively associated with mental health problems in normal adults (p<0.05). Normal adults had higher level of mental health problems, such as depression and stress, compared to deliberate self harm adults (p<0.05). Adults having self-harm behaviour were more inclined to have suicidal ideation compared to normal adults behaviour (p<0.05). Deliberate self-harm was found to be strongly related to suicidal behaviour and mental health issues in both normal and deliberate self-harm adults.


Globin-like proteins in Caenorhabditis elegans: in vivo localization, ligand binding and structural properties.
The genome of the nematode Caenorhabditis elegans contains more than 30 putative globin genes that all are transcribed. Although their translated amino acid sequences fit the globin fold, a variety of amino-acid substitutions and extensions generate a wide structural diversity among the putative globins. No information is available on the physicochemical properties and the in vivo expression. We expressed the globins in a bacterial system, characterized the purified proteins by optical and resonance Raman spectroscopy, measured the kinetics and equilibria of O2 binding and determined the crystal structure of GLB-1* (CysGH2 --> Ser mutant). Furthermore, we studied the expression patterns of glb-1 (ZK637.13) and glb-26 (T22C1.2) in the worms using green fluorescent protein technology and measured alterations of their transcript abundances under hypoxic conditions.GLB-1* displays the classical three-over-three alpha-helical sandwich of vertebrate globins, assembled in a homodimer associated through facing E- and F-helices. Within the heme pocket the dioxygen molecule is stabilized by a hydrogen bonded network including TyrB10 and GlnE7.GLB-1 exhibits high ligand affinity, which is, however, lower than in other globins with the same distal TyrB10-GlnE7 amino-acid pair. In the absence of external ligands, the heme ferrous iron of GLB-26 is strongly hexacoordinated with HisE7, which could explain its extremely low affinity for CO. This globin oxidizes instantly to the ferric form in the presence of oxygen and is therefore incapable of reversible oxygen binding. The presented data indicate that GLB-1 and GLB-26 belong to two functionally-different globin classes.


Human cadaver model as a training tool for enzymatic burn debridement (Nexobrid®): A feasibility study.
To determine the feasibility of using human cadavers to demonstrate enzymatic burn debridement, as a training aid for clinical staff. A single, fresh-frozen human cadaver was used. Prior consent had been given. Burns were created by flame and scalding. Unburned control sites were also assessed. Nexobrid® enzymatic burn debridement paste was applied to all sites, in adherence to the local clinical protocol for treating burned patients. After removal of Nexobrid®, wounds were assessed to determine if the cadaveric tissue appeared similar to what would be expected in living burned patients and whether the technique could be viable for training of burn care staff. Nexobrid® had a very similar effect upon burned cadaveric skin to what would have been expected in living burned skin. Burns of partial thickness burn depth and full thickness burn depth were debrided and could be clearly identified. Fresh-frozen human cadaveric tissue is a valid means of provision of training in the technique of enzymatic burn debridement. This finding was unexpected and shows that our understanding of the mechanism of action of Nexobrid® is incomplete.


Co-remediation of PTEs contaminated soil in mining area by heat modified sawdust and herb.
Exploring efficient remediation technologies to remediate potentially toxic element (PTE) in soil around the mining area has become a trendy research topic. This study conducted material composed of sawdust ash (SA) and sawdust biochar (SB) with mass ratio of SA:SB = 1:2 in combination with Medicago sativa L. and Festuca arundinacea to remediate soil contaminated by zinc (Zn), cadmium (Cd), and arsenic (As) in a mining area. The result showed that the removal rates of Zn, Cd, and As were the highest under the treatment of Festuca arundinacea combined with 5% material with values of 22.15%, 22.05%, and 12.47%, respectively. Festuca arundinacea had the most potent ability to absorb and tolerate composite PTEs, and the co-remediation process could remarkably improve soil enzyme environment and microbial community diversity. The distribution of PTEs in plant subcellular showed that the accumulation of Zn, Cd, and As in the cell wall of Festuca arundinacea root was significantly increased by adding 2% materials. The concentrations of Zn, Cd, and As in the cell wall were 4486.25, 33.59, and 124.15 mg/kg, respectively. The combination of 2% material and Festuca arundinacea could effectively remove PTEs in soil and enhance the detoxification ability of the plant, thus effectively improving the soil environment and remediating PTEs pollution. This study provided insights into the remediation of PTE-contaminated soil in mining area by combining materials and plants.


CD5+ B-cell lymphoproliferative disorders: Beyond chronic lymphocytic leukemia and mantle cell lymphoma.
CD5 positivity in B-cell lymphoproliferative disorders (LPD) is usually considered characteristic of either chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). However, other neoplastic B-LPDs may express CD5, albeit infrequently. In this study we have reviewed the tissue pathology of CD5+ B-LPDs that do not fulfill diagnostic criteria for CLL or MCL on flow cytometric studies of peripheral blood or bone marrow. Our results indicate that although CD5 positivity is most commonly associated with CLL and MCL, a significant minority of cases do not fall into these two categories. Phenotypically unusual CLL, marginal zone lymphoma and lymphoplasmacytic lymphoma were the most common diagnoses in this group of patients. Applying strict flow cytometry criteria, using genetic studies, and deferring to a lymph node/tissue diagnosis in non-classical cases are critical for accurate diagnosis and classification of CD5+ B-cell LPD.


Synthetic immunostimulants (excluding sulfur-containing compounds).
Many different approaches have been used, over the last 15 years, for the design of potential immunostimulating drugs: Fractionation of crude natural substances (of eukaryotic or prokaryotic origin) already known to enhance immune functions, followed by chemical characterization and, in many cases, full synthesis of the active moiety: examples are provided by thymic hormones and the muramyldipeptide (MDP); Chemical modification of natural substances of known chemical structure in order to potentiate or change their biological activities or reduce their toxicity: murabutide, lipophilic MDP derivatives, lipopeptides (such as pimelautide), tuftsin analogs; Chemical synthesis (often without preconceived ideas about structure-activity relationship) of a great variety of molecules which are then screened in vitro and in vivo for immunopharmacological activity. The chemical structures and the biological profiles (in terms of possible primary cellular targets and mechanisms of immunostimulating activities) of representatives of class (b) and class (c) immunostimulants are reviewed in this paper.


Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT.
A high expression of fibroblast activation protein (FAP) was observed in multiple sarcomas, indicating an enormous potential for PET/CT using 68Ga-radiolabeled inhibitors of FAP (FAPI). Therefore, this retrospective study aimed to evaluate the role of the novel hybrid imaging probe for sarcomas as a first clinical evaluation. A cohort of 15 patients underwent 68Ga-FAPI-PET/CT for staging or restaging. The acquisition of PET scans was performed 60 min after administration of 127 to 308 MBq of the tracer. The uptake of 68Ga-FAPI in malignant tissue as well as in healthy organs was quantified by standardized uptake values SUVmean and SUVmax. Excellent tumor-to-background ratios (> 7) could be achieved due to low background activity and high SUVmax in primary tumors (median 7.16), local relapses (median 11.47), and metastases (median 6.29). The highest uptake was found for liposarcomas and high-grade disease (range 18.86-33.61). A high SUVmax (> 10) was observed for clinically more aggressive disease. These preliminary findings suggest a high potential for the clinical use of 68Ga-FAPI-PET/CT for patients diagnosed with sarcoma.


Alternative splicing during fruit development among fleshy fruits.
Alternative splicing (AS) is an important mechanism of posttranscriptional modification and dynamically regulates multiple physiological processes in plants, including fruit ripening. However, little is known about alternative splicing during fruit development in fleshy fruits. We studied the alternative splicing at the immature and ripe stages during fruit development in cucumber, melon, papaya and peach. We found that 14.96-17.48% of multiexon genes exhibited alternative splicing. Intron retention was not always the most frequent event, indicating that the alternative splicing pattern during different developmental process differs. Alternative splicing was significantly more prevalent at the ripe stage than at the immature stage in cucumber and melon, while the opposite trend was shown in papaya and peach, implying that developmental stages adopt different alternative splicing strategies for their specific functions. Some genes involved in fruit ripening underwent stage-specific alternative splicing, indicating that alternative splicing regulates fruits ripening. Conserved alternative splicing events did not appear to be stage-specific. Clustering fruit developmental stages across the four species based on alternative splicing profiles resulted in species-specific clustering, suggesting that diversification of alternative splicing contributes to lineage-specific evolution in fleshy fruits. We obtained high quality transcriptomes and alternative splicing events during fruit development across the four species. Dynamics and nonconserved alternative splicing were discovered. The candidate stage-specific AS genes involved in fruit ripening will provide valuable insight into the roles of alternative splicing during the developmental processes of fleshy fruits.


Allergic diseases and asthma in pregnancy, a secondary publication.
Every fifth pregnant woman is affected by allergies, especially rhinitis and asthma. Allergic symptoms existing before pregnancy may be either attenuated, or equally often promoted through pregnancy. Optimal allergy and asthma diagnosis and management during pregnancy is vital to ensure the welfare of mother and baby. For allergy diagnosis in pregnancy, preferentially anamnestic investigation as well as in vitro testing should be applied, whereas skin testing or provocation tests should be postponed until after birth. Pregnant women with confirmed allergy should avoid exposure to, or consumption of the offending allergen. Allergen immunotherapy should not be initiated during pregnancy. In patients on immunotherapy since before pregnancy, maintenance treatment may be continued, but the allergen dose should not be increased further. Applicable medications for asthma, rhinitis or skin symptoms in pregnancy are discussed and listed. In conclusion, i) allergies in pregnancy should preferentially be diagnosed in vitro; ii) AIT may be continued, but not started, and symptomatic medications must be carefully selected; iii) management of asthma and allergic diseases is important during pregnancy for welfare of mother and child.


Image-based monitoring of magnetic resonance-guided thermoablative therapies for liver tumors.
Minimally invasive treatment options for liver tumor therapy have been increasingly used during the last decade because their benefit has been proven for primary and inoperable secondary liver tumors. Among these, radiofrequency ablation has gained widespread consideration. Optimal image-guidance offers precise anatomical information, helps to position interventional devices, and allows for differentiation between already-treated and remaining tumor tissue. Patient safety and complete ablation of the entire tumor are the overriding objectives of tumor ablation. These may be achieved most elegantly with magnetic resonance (MR)-guided therapy, where monitoring can be performed based on precise soft-tissue imaging and additional components, such as diffusion-weighted imaging and temperature mapping. New MR scanner types and newly developed sequence techniques have enabled MR-guided intervention to move beyond the experimental phase. This article reviews the current role of MR imaging in guiding radiofrequency ablation. Signal characteristics of primary and secondary liver tumors are identified, and signal alteration during therapy is described. Diffusion-weighted imaging (DWI) and temperature mapping as special components of MR therapy monitoring are introduced. Practical information concerning coils, sequence selection, and parameters, as well as sequence gating, is given. In addition, sources of artifacts are identified and techniques to decrease them are introduced, and the characteristic signs of residual tumor in T1-, T2-, and DWI are described. We hope to enable the reader to choose MR sequences that allow optimal therapy monitoring depending on the initial signal characteristics of the tumor as well as its size and location in the liver.


Sequential study of echocardiographic changes in purulent pericarditis.
Serial echocardiographic studies were performed in a child with purulent pericarditis. Besides demonstrating the pericardial effusion, echocardiography was used to assess cardiac function. Computer analysis of changes in left ventricular dimension showed impaired diastolic filling, persisting after pericardiocentesis but normalizing after pericardiectomy.


Use of enzyme-linked immunosorbent assay for the diagnosis of equine Histoplasmosis farciminosi (epizootic lymphangitis).
An enzyme-linked immunosorbent assay was evaluated for the detection of antibody in sera of equine naturally infected with Histoplasma farciminosum 'epizootic lymphangitis'. Ten sera from naturally infected horses were tested. A hydrogen peroxide ABTS mixture constituted the substrate. The reactions were read as the absorbance values measured at 405 nm using a spectrophotometer. The standard deviation and the average percentage of the absorbance values of the different serum samples were considered in the interpretation of the results. All sera were proved positive with variations in the different samples. Ground preparation of four weeks old growth of the fungus in a phosphate buffer saline was used as antigen. A peroxidase labeled goat anti-equine IgG was used as a conjugate.


Development of a novel near-infrared fluorescent theranostic combretastain A-4 analogue, YK-5-252, to target triple negative breast cancer.
The treatment of triple negative breast cancer (TNBC) is a significant challenge to cancer research. The lack of hormone receptors limits the treatment options available to patients with this diagnosis, forcing them to endure prolonged radiation and chemotherapy. Anti-angiogenesis is a chemotherapeutic strategy that targets the vasculature of tumors. Combretastatin A-4 (CA-4) is a well-known vasculature-disrupting agent, which has been shown to effectively kill a variety of cancers through inhibition of tubulin polymerization. Due to its toxicity, small molecule analogues of CA-4 have been sought out. We have designed a novel dual action CA-4 prodrug, YK-5-252, which releases the drug through a disulfide bond cleavage mechanism and contains a near-infrared (NIR) fluorophore, which allows fluorescence monitoring of cleavage. This disulfide linkage causes CA-4 to become effective only when released by glutathione (GSH) reducing the toxicity of the drug while simultaneously releasing the NIR fluorophore. Therefore the prodrug, YK-5-252, represents a novel CA-4 analogue which has reduced toxicity and can be used for theranostics imaging.


Body composition in adults with newly diagnosed type 2 diabetes: effects of metformin.
The aim of this study was to measure the body composition in adults with newly diagnosed type 2 diabetes mellitus and to explore the effect of metformin therapy on the various components of body composition, insulin sensitivity, and glucose homeostasis. This was an observational study consisted of 51 newly diagnosed people with type 2 diabetes on 1000 mg metformin twice daily for 6 months. The body composition of each subject was measured by dual energy X-ray absorptiometry at enrollment and 24 weeks after metformin mono-therapy. Sarcopenia was defined and compared based on the ratio of appendicular skeletal muscle and height squared, skeletal muscle index and residual methods. Homeostasis model assessment-insulin resistance and Quantitative Insulin Sensitivity Check Index were used for estimating insulin sensitivity. The level of physical activity was assessed using self-administered International physical Activity questionnaire. Forty one subjects (80.4%) completed the study. The mean age of the participants was 52.67 ± 10.43 years. Metformin treatment was associated with a significant decrease in total fat mass (-1.6 kg, P = 0.000). By week 24, the lean to fat ratio increased (P = 0.04) with men showing greater significant changes. Twenty percent of the female participants were detected to have sarcopenia. In addition, there was a significant improvement of glucose homeostasis and insulin sensitivity. Metformin therapy results in significant improvement in body composition and insulin sensitivity of adults with newly diagnosed type 2 diabetes. Furthermore, sarcopenia begins in women with diabetes much earlier than expected as an age related phenomenon.


Counter current "emulsion flow" extractor for continuous liquid-liquid extraction from suspended solutions.
A single current "emulsion flow" liquid-liquid extraction apparatus has a head with a number of holes from which micrometer-sized droplets of an aqueous phase spout into an organic phase to mix the two liquid phases. For practical use, however, a fatal problem can occur when particulate components in the aqueous phase plug the holes. In the present study, we have succeeded in solving the problem by applying a counter current-type emulsion flow extractor where micrometer-sized droplets of the organic phase are generated.


Reference genomes of channel catfish and blue catfish reveal multiple pericentric chromosome inversions.
Channel catfish and blue catfish are the most important aquacultured species in the USA. The species do not readily intermate naturally but F1 hybrids can be produced through artificial spawning. F1 hybrids produced by mating channel catfish female with blue catfish male exhibit heterosis and provide an ideal system to study reproductive isolation and hybrid vigor. The purpose of the study was to generate high-quality chromosome level reference genome sequences and to determine their genomic similarities and differences. We present high-quality reference genome sequences for both channel catfish and blue catfish, containing only 67 and 139 total gaps, respectively. We also report three pericentric chromosome inversions between the two genomes, as evidenced by long reads across the inversion junctions from distinct individuals, genetic linkage mapping, and PCR amplicons across the inversion junctions. Recombination rates within the inversional segments, detected as double crossovers, are extremely low among backcross progenies (progenies of channel catfish female × F1 hybrid male), suggesting that the pericentric inversions interrupt postzygotic recombination or survival of recombinants. Identification of channel catfish- and blue catfish-specific genes, along with expansions of immunoglobulin genes and centromeric Xba elements, provides insights into genomic hallmarks of these species. We generated high-quality reference genome sequences for both blue catfish and channel catfish and identified major chromosomal inversions on chromosomes 6, 11, and 24. These perimetric inversions were validated by additional sequencing analysis, genetic linkage mapping, and PCR analysis across the inversion junctions. The reference genome sequences, as well as the contrasted chromosomal architecture should provide guidance for the interspecific breeding programs.


Regulation of Weibel-Palade body exocytosis.
Weibel-Palade bodies (WPBs) are endothelial granules that store von Willebrand factor (VWF), P-selectin, and other vascular modulators. Endothelial cells secrete WPBs in response to vascular injury, releasing VWF, which triggers platelet rolling, and externalizing P-selectin, which activates leukocyte trafficking. Endothelial exocytosis is one of the earliest responses to vascular damage and plays a pivotal role in thrombosis and inflammation. This review examines the regulation of WPB exocytosis-the exocytic machinery, activators, and inhibitors of exocytosis-and speculates about the development of novel anti-exocytic drugs.


Aortic sepsis: is there a role for in situ graft reconstruction?
Conventional extraanatomic reconstruction for aortic sepsis is associated with a significant risk of operative death, as well as frequent late complications. We evaluated in situ aortic grafting in the treatment of primary or graft-related aortic infection. Eleven selected patients underwent in situ aortic graft reconstruction in the setting of mycotic aneurysm (n = 5), secondarily infected aortic aneurysm (n = 1), primary aortoenteric fistula (n = 1), and secondary aortoenteric fistula (n = 4). All patients survived: follow-up from 10 to 130 months reveals no evidence for graft thrombosis, pseudoaneurysm, new or recurrent aortoenteric fistula, or subsequent aortic operations in any patient. A literature review produced 110 cases of aortic sepsis managed by in situ aortic reconstruction during the last decade. Thirty-two patients (29%) either died in the operative period or suffered a lethal late complication associated with their aortic reconstruction. This mortality rate declined to 21% if patients undergoing incomplete removal of a contaminated graft were excluded, and to 19% with the addition of our 11 patients. Both our experience and that described in the literature suggest that, in properly-selected patients, in situ aortic graft replacement may be a rational treatment option for localized or circumscribed aortic sepsis.


Impact of timing and setting of palliative care referral on quality of end-of-life care in cancer patients.
Limited data are available on how the timing and setting of palliative care (PC) referral can affect end-of-life care. In this retrospective cohort study, the authors examined how the timing and setting of PC referral were associated with the quality of end-of-life care. All adult patients residing in the Houston area who died of advanced cancer between September 1, 2009 and February 28, 2010 and had a PC consultation were included. Data were retrieved on PC referral and quality of end-of-life care indicators. Among 366 decedents, 120 (33%) had an early PC referral (>3 months before death), and 169 (46%) were first seen as outpatients. Earlier PC referral was associated with fewer emergency room visits (39% vs 68%; P<.001), fewer hospitalizations (48% vs 81%; P<.003), and fewer hospital deaths (17% vs 31%; P5.004) in the last 30 days of life. Similarly, outpatient PC referral was associated with fewer emergency room visits (48% vs 68%; P<.001), fewer hospital admissions (52% vs 86%; P<.001), fewer hospital deaths (18% vs 34%; P5.001), and fewer intensive care unit admissions (4% vs 14%; P5.001). In multivariate analysis, outpatient PC referral (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.28-0.66; P<.001) was independently associated with less aggressive end-of-life care. Men (OR, 1.63; 95% CI, 1.06-2.50; P5.03) and hematologic malignancies (OR, 2.57; 95% CI, 1.18-5.59; P5.02) were associated with more aggressive end-of-life care. Patients who were referred to outpatient PC had improved end-of-life care compared with those who received inpatient PC. The current findings support the need to increase the availability of PC clinics and to streamline the process of early referral.


Three-dimensional computed tomography-guided multitract aspiration of extensive ganglionic hemorrhage: technical note.
We describe a methodology for effectively improving the lysis and drainage of intracerebral hematomas during stereotactic surgery. Stereotactic aspiration using a multitrack technique was performed in 20 patients with ganglionic hemorrhages perforating into the subcortex. Using 3-dimensional computed tomography (3D-CT) guidance, the trajectories and targets of hematoma drainage were selected to extract most portions of the irregular and expansive intracerebral hematomas. Volumes ranged from 36 to 60 mL (mean, 45 mL). Four to 5 drains were inserted into the parenchymal and ventricular clots. Aspiration and injections of urokinase (5000 IU) were repeated every 2 to 3 hours until the hematoma was almost completely removed. The intended catheters for hematoma aspiration were placed precisely along the predetermined tracks with the aid of 3D-CT visualization. The deep and subcortical hematomas were totally removed within a mean of 10 hours postoperatively. Multiple catheter placements itself caused no complications. Sixteen patients (80%) recovered with a favorable neurological outcome. The 3D-CT-based multitrack technique is a rapid and effective method for the stereotactic removal of extensive ganglionic hemorrhages. It has the advantage of giving better neurological recovery than conventional stereotactic or microscopic surgery for selected patients.


SERS-based test strips: Principles, designs and applications.
Test strips represent a class of point-of-care testing (POCT) tools for analysis of a variety of biomarkers towards diagnostics. Conventional test strips offer benefits of simple operation, visualization, and short detection time, along with the drawbacks of relatively low sensitivity and unavailability of quantitative analysis. Recently, the combination of surface-enhanced Raman scattering (SERS) and test strips have evolved to provide a powerful platform capable of ultrasensitive and multiplex detection of extensive analytes of interest. In this review, we focus on the working principles, design strategies and POCT applications of SERS-based test strips. Initially, both lateral and vertical flow test strips are briefly introduced, followed by presentation of various strategies for reforming SERS-based test strips with better detection performance. Applications of SERS-based test strips in diagnosis of disease biomarkers, nucleic acids and toxins are reviewed, with an emphasis on SERS tag design, sensitivity and analytical applicability. Finally, conclusions are made and perspectives on futuristic research directions are given.


Group versus individual exposure: Do methodological decisions in aquatic toxicology alter experimental results?
In aquatic toxicology, methods that are chosen for exposures have profound consequences on experimental outcomes and thus can skew policy initiatives. For example, as compared to single-organism exposures, toxicity test results of group exposures may be impacted by confounding factors such as social interactions between animals or individual variation in accumulation rates. To test for differences in organismal response between group and individual toxicological exposures, we exposed Daphnia magna to copper and subsequently compared the toxicity (median lethal concentration or LC50) between groups and individuals. Results suggested that water chemistry had a larger effect on experimental outcomes than the number of animals exposed in the same tank. Methodological decisions with respect to replication type can affect toxicity tests, and LC50s calculated using different exposure types (such as group and individual exposures) may not be comparable.


Prevalence and Pregnancy Outcome of Mullerian Anomalies in Infertile Women: A Retrospective Study.
Uterine anomalies arise if there is agenesis of one or two mullerian ducts, or absence of fusion or reabsorption of the septum between these ducts. The process may be partial or total and affect one or multiple parts of the tract. This study was done to assess the distribution of various types of mullerian anomalies in infertile women, their classification based on ESHRE and AFS, associated anomalies, types of diagnostic modalities used, surgical interventions done(if any), various types of infertility treatment used and their outcomes. A retrospective analysis in a tertiary level hospital. This was a retrospective study in which the women found to have mullerian anomalies were recruited from infertility clinic from July 2019 to March 2020. They were classified according to ESHRE and AFS criteria and their records were analyzed after taking various factors like age, ovarian reserve, duration of infertility, treatment given , associated ovarian and tubal factors and pregnancy outcomes. Analysis was performed in Excel. There were 30 women with mullerian anomalies. Unicornuate uterus was most common anomaly. Four women required septoplasty in view of septate uterus. Five women had associated renal anomalies in form of shrunken kidney and ectopic kidney. Most of these women were considered for controlled ovarian stimulation followed by intrauterine insemination. In our study 16.6% women had successful pregnancy outcome. Mullerian anomalies continue to attract infertility specialist as they pose challenge in making clear diagnosis and its management as obstetrics outcomes are excellent after septum resection in women with septate uterus and conservative management in women with other anomalies. Proper work up of infertility and its management varies from case to case and associated factors like endometriosis, male factor, polycystic ovarian syndrome etc.


Combination of Compound Kushen Injection and cisplatin shows synergistic antitumor activity in p53-R273H/P309S mutant colorectal cancer cells through inducing apoptosis.
Colorectal cancer (CRC) is one type of worldwide popular and refractory tumors. Compound Kushen Injection (CKI) is a frequently applied traditional Chinese medicine formula as an adjuvant drug for the chemotherapy of CRC. P53 is the most commonly mutated gene in CRC, accounting for the development, malignant and prognosis progression of CRC. However, effect of CKI on the therapeutic efficacy of p53-mutant CRC remains understood. Besides, the combined efficacy of different chemotherapeutics drugs in combination with CKI for CRC treatment is rarely concerned. To investigate the combined efficacy of the CKI-derived combination strategies in the p53-mutant CRC. Two CRC cell lines HCT116 and SW480 cells, which respectively harbor wild-type p53 and p53-R273H/P309S mutant, were applied. Cisplatin (Cis) and 5-fluorouracil (5FU) were combined chemotherapeutics drugs of CKI-derived combination strategies in this article. In vitro antitumor activity was detected by sulforhodamine B (SRB) assay and colony formation assay. Combenefit soft was applied to evaluate the synergetic/antagonistic effect of drug combination. Lentivirus-mediated overexpression method was used to generate a set of p53-mutant and wild-type CRC cell lines harboring identical genomes. Transcriptomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were applied to predicate the underlying mechanism of synergetic interaction between drug combination. Western blot was performed to verify predicated pathways contributing to the synergy of drug combination. CKI preferentially combined with Cis but not 5FU, to produce a synergistical antitumor efficiency for p53-R273H/P309S mutant, rather than wild-type p53 harboring CRC cells. The combination of CKI and Cis strongly reprogrammed the transcriptional profiles of SW480 cells. Cytokine-cytokine receptor interaction pathway was a key pathway involved in cooperativity between CKI and Cis in SW480 cells. Mechanistically, compared to that Cis individually triggered necroptosis, the co-treatment of CKI and Cis reinforced the cell death of SW480 cells in a possible synergistic manner by inducing extrinsic apoptosis pathway. This article provides a novel perspective into the precision clinical application of CKI-derived combination therapy programs of CRC based on genetic variation and the classes of chemotherapeutics drugs.


Tertiary osteochondral defect of the talus treated by a novel contoured metal implant.
The primary treatment of most osteochondral defects of the talus is arthroscopic debridement and bone marrow stimulation. There is no optimal treatment for large lesions or for those in which primary treatment has failed. We report a 20-year-old female patient with persistent symptoms after two previous arthroscopic procedures. Computed tomography showed a cystic defect of the medial talar dome, sized 17×8×8 mm. The patient was treated with a novel contoured metal implant. At 1 and 2 years after surgery, the patient reported considerable reduction in pain and had resumed playing korfball at competitive level. Level of evidence IV.


The 56 kDa androgen-binding protein in human genital skin fibroblasts: its relation to the human androgen receptor.
We have recently described in genital skin fibroblasts (GSF) a relatively abundant 56 kDa protein with androgen-binding activity. This protein is missing in GSF of most patients with complete androgen insensitivity syndrome (CAI). The protein has many characteristics compatible with the androgen receptor; it has in fact been tentatively considered as a precursor or degradation form of the prototypic (approximately 100 kDa) human androgen receptor. We have prepared an antiserum to this protein, which allowed us to detect it as a direct product by in vitro translation of mRNA from GSF. It is thus very unlikely to be a degradation product of a larger precursor. Furthermore, covalent photolytic labeling of this protein with the androgen analogue [3H]mibolerone revealed a much lower affinity for this protein than is known for the androgen receptor. Finally, the GSF of two exceptional patients with complete androgen insensitivity syndrome due to negligible androgen receptor-binding activity express this protein normally, as determined on two-dimensional gels by Western blot analysis with the antiserum and by photolytic covalent labeling with androgen analogues. These data indicate that the protein is not a precursor or a degradation product of the receptor; nor is it androgen-induced. They are more compatible with the idea that the protein is another member of the steroid/thyroid/retinoic acid receptor supergene family, perhaps as an unorthodox product of the human androgen receptor gene.


Study of levocetirizine in seasonal allergic rhinitis.
To evaluate the efficacy of levocetirizine 5 mg once daily in reducing seasonal allergic rhinitis (SAR) symptoms in US adults. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled adults aged 18 to 65 years with SAR symptoms in the spring in the US. After a single-blind placebo run-in period, subjects received levocetirizine 5 mg or placebo once daily over 14 days. ClinicalTrials.gov registry no.: NCT00621959. Primary efficacy variable was the Total 5-Symptom Score (T5SS). Secondary variables included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment-Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS). Safety assessments were based on adverse events (AEs). The intent-to-treat population comprised 596 subjects (levocetirizine, n = 301; placebo, n = 295). Comparison of mean T5SS over the total treatment period showed a nonsignificant between-group difference (levocetirizine, 8.90 +/- 0.19; placebo, 9.04 +/- 0.19; adjusted mean difference, -0.14; p = 0.546). Levocetirizine showed numerical (mean RQLQ, WPAI-AS, ESS) and statistically superior differences (two domains within WPAI-AS) compared with placebo upon analysis of secondary efficacy variables. The incidence of treatment-emergent AEs was similar (levocetirizine, 23.9%; placebo, 24.4%). As the lack of efficacy was inconsistent with all previous levocetirizine studies, post hoc analyses were performed to assess the influence of pollen counts, geography, and other factors; however, no conclusive explanation could be identified. In this study, levocetirizine 5 mg QD was well tolerated but failed to show significant efficacy compared with placebo in a US adult population with SAR. This finding is inconsistent with all previous studies with levocetirizine and in contrast to a concurrently run, similarly designed US study. It reflects the importance of conducting duplicate studies as there is always a small but real risk of false negative results in clinical studies, irrespective of the methodologic quality.


Detection of fetal arrhythmia by adaptive single channel electrocardiogram extraction.
Fetal arrhythmia, the abnormal heartbeat of a fetus is broadly classified as tachy arrhythmia (too fast > 160 beats/min) and brady arrhythmia (too slow < 120 beats/min). Detection of this irregular heart beat rhythm of the fetus during pregnancy is still a challenging task for the clinicians. Heart rate detection through electrocardiography has always been accurate for identifying cardiac defect in humans. Adult ECG has achieved several developments in the modern medicine whereas noninvasive fetal ECG (FECG) continues to be a big challenge. Automatic detection of fetal heart rate is vital for monitoring the unborn infant during pregnancy. The non-invasive placement of electrodes over the abdomen region of pregnant women records the ECG signal of both mother and fetus. The arrhythmia affected FECG signals (n = 14) are processed from the physionet database. This raw ECG signal is preprocessed using a Savitzky-Golay filter and symlet wavelet transform to remove the basic noises. Adaptive recursive least square filter is preferably chosen for extracting the FECG, using mother's thorax ECG as a reference. An accurate PQRST wave-shape of the FECG is required for the proper diagnosis of fetal cardiac defects. Using a single channel abdominal ECG signal, the proposed work generates extracted fetal ECG and an automated visual display of fetal heart rate. The presence of arrhythmia and fetal distress can be analyzed through fetal heart rate display and abnormal conductivity of PQRST wave respectively. We have analyzed fetal arrhythmias through ECG extraction and the same was compared with the echocardiograph results given by pediatric cardiologist. This study helps to identify the fetal distress at early gestational age that helps the obstetricians to make quick decisions before or immediately after delivery.


Hydrogels to model 3D in vitro microenvironment of tumor vascularization.
A growing number of failing clinical trials for cancer therapy are substantiating the need to upgrade the current practice in culturing tumor cells and modeling tumor angiogenesis in vitro. Many attempts have been made to engineer vasculature in vitro by utilizing hydrogels, but the application of these tools in simulating in vivo tumor angiogenesis is still very new. In this review, we explore current use of hydrogels and their design parameters to engineer vasculogenesis and angiogenesis and to evaluate the angiogenic capability of cancerous cells and tissues. By coupling these hydrogels with other technologies such as lithography and three-dimensional printing, one can create an advanced microvessel model as microfluidic channels to more accurately capture the native angiogenesis process.


Stimulation of anti-tumour immunity in guinea-pigs by methanol extraction residue of BCG.
The immunoprophylactic effects of the methanol extraction residue (MER) of BCG were investigated in Strain 2 guinea-pigs injected with cells of the transplantable, diethylnitrosamine-induced, Line 10 hepatocarcinoma. Pretreatment with MER at times ranging from 18 to 182 days prior to tumour implantation protected approximately 40% of guinea-pigs from progressive neoplastic disease. In addition, MER-treated animals developed specific cell-mediated anti-tumour immunity both more rapidly and at higher levels than did non-MER-treated tumour-bearing controls. It was not possible, however, to prognosticate from the results of such laboratory studies to the outcome of immunoprophylaxis.


Physically fit with a higher cancer risk? Influences of cervical cancer screening among a sample of physically active women ages 21-49 living in the United States.
To achieve the lowest risk level for various cancers, individuals would engage in several healthy lifestyle behaviors and age-eligible cancer screenings as recommended. Nonetheless, research has largely omitted exploration of concurrent primary and secondary prevention behaviors. This study was designed to explore influences of cervical cancer screening among physically active women who reported participation in recreational sports. U.S. based women between the ages of 21-49, who had never been diagnosed with cancer, were eligible to complete a web-based survey. Logistic regression analyses were conducted using SAS 9.4. On average, women were 31 years of age (N = 394) and self-identified as Black (51.3 %). Although low overall (30.7 %), higher odds of cervical cancer screening were associated with age (OR = 1.06, 95 % CI = 1.03-1.10), employment (OR = 2.43, 95 % CI = 1.14-5.18), knowledge of cancer-related risk behaviors (OR = 4.04, 95 % CI = 1.33-12.28), routine doctor's visit (OR = 4.25, 95 % CI = 1.56-11.54), and team-based vs individual-based sport participation (OR = 1.95, 95 % CI = 1.13-3.34). Our study provides insight into the health profile of physically active women, ages 21-49, as it relates to risks for cervical cancer. Screening uptake among this diverse sample was much lower than the general population and national goals set by Healthy People 2030. Interventions should be tailored to increase knowledge of cancer-related risk behaviors, access to healthcare, and recommended cervical cancer screenings among even assumed-to-be healthy populations.


The major outer sheath protein of Treponema denticola selectively inhibits Rac1 activation in murine neutrophils.
Treponema denticola major outer sheath protein (Msp) inhibits neutrophil chemotaxis in vitro, but key regulatory mechanisms have not been identified. Because the Rac small GTPases regulate directional migration in response to chemoattractants, the objective was to analyse the effects of Msp on formyl-methionyl-leucyl-phenylalanine (fMLP)-mediated neutrophil polarization and Rac activation in murine neutrophils. Msp pretreatment of neutrophils inhibited both polarization and chemotactic migration in response to fMLP. Activation of small GTPases was measured by p21 binding domain (PBD) pulldown assays, followed by Western analysis, using monoclonal anti-Rac1, anti-Rac2, anti-cdc42 and anti-RhoA antibodies. Enriched native Msp selectively inhibited fMLP-stimulated Rac1 activation in a concentration-dependent manner, but did not affect Rac2, cdc42 or RhoA activation. Murine neutrophils transfected with vectors expressing fluorescent probes PAK-PBD-YFP and PH-AKT-RFP were used to determine the effects of Msp on the localization of activated Rac and PI3 kinase products. Real-time confocal images showed that Msp inhibited the polarized accumulation of activated Rac and PI3-kinase products upon exposure to fMLP. The findings indicate that T. denticola Msp inhibition of neutrophil polarity may be due to the selective suppression of the Rac1 pathway.