Magnetic resonance imaging of normal and osteoarthritic trabecular bone structure in the human knee.
To use high-resolution magnetic resonance imaging (MRI) to evaluate the trabecular bone structure in the distal femur and the proximal tibia and its to correlate the findings with different stages of osteoarthritis (OA) of the human knee. Axial images of the distal femur and proximal tibia were obtained at 1.5 T in patients without and with mild OA and with severe OA. The spatial resolution was 195 x 195 microm(2) with a 1-mm slice thickness. Apparent measures of trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular separation (Tb.Sp), and trabecular thickness (Tb.Th) were calculated. Significant differences existed in the trabecular bone structure of the femur and tibia. Differences in trabecular bone structure between the tibia and the femur decreased with the degree of OA. The apparent BV/TV, Tb.N, and Tb.Sp in the femoral condyles could be used to differentiate healthy patients or patients with mild OA from patients with severe OA (P < 0.05). Among individuals, the structural variation of the lateral and medial femoral condyle was indicative of the extent of the disease. High-resolution MRI of the knee joint can provide a noninvasive assessment of trabecular bone structure. Trabecular bone structure, determined by high-resolution MRI, shows significant variation in patients with varying degrees of OA. The impact of OA on trabecular bone is different in the tibia than in the femur, and this difference depends on the extent of the disease.


Meniscal repair failure following concurrent primary anterior cruciate ligament reconstruction: results from the New Zealand ACL Registry.
This study aimed to identify the risk factors for meniscal repair failure following concurrent primary anterior cruciate ligament (ACL) reconstruction. Prospective data recorded by the New Zealand ACL Registry and the Accident Compensation Corporation were reviewed. Meniscal repairs performed during concurrent primary ACL reconstruction were included. Repair failure was defined as a subsequent reoperation involving meniscectomy of the repaired meniscus. Multivariate survival analysis was performed to identify the risk factors for failure. A total of 3,024 meniscal repairs were analysed with an overall failure rate of 6.6% (n = 201) at a mean follow-up of 2.9 years (SD 1.5). The risk of medial meniscal repair failure was higher with hamstring tendon autografts (adjusted HR [aHR] = 2.20, 95% CI 1.36-3.56, p = 0.001), patients aged 21-30 years (aHR = 1.60, 95% CI 1.30-2.48, p = 0.037) and in patients with cartilage injury in the medial compartment (aHR = 1.75, 95% CI 1.23-2.48, p = 0.002). The risk of lateral meniscal repair failure was higher in patients aged ≤ 20 years (aHR = 2.79, 95% CI 1.17-6.67, p = 0.021), when the procedure was performed by a low case volume surgeon (aHR = 1.84, 95% CI 1.08-3.13, p = 0.026) and when a transtibial technique was used to drill the femoral graft tunnel (aHR = 2.30, 95% CI 1.03-5.15, p = 0.042). The use of a hamstring tendon autograft, younger age and the presence of medial compartment cartilage injury are risk factors for medial meniscal repair failure, whereas younger age, low surgeon volume and a transtibial drilling technique are risk factors for lateral meniscal repair failure. Level II.


L3 and adult Ostertagia (Teladorsagia) circumcincta exhibit cyanide sensitive oxygen uptake.
Oxygen consumption by L3 and adult Ostertagia (Teladorsagia) circumcincta was examined in vitro to determine whether oxygen can be utilised in metabolism. The oxygen concentration in the abomasal fluid of sheep infected with O. circumcincta was also measured. Rates of consumption (in nmol O2/h/1000 worms) were 13+/-1 in sheathed L3, 34+/-6 in ex-sheathed L3, and 1944+/-495 in adult worms. Constant rates of consumption were maintained until media oxygen concentration dropped to between 10 and 20 microM. Consumption was inhibited 95% by cyanide in L3 and 74% in adults. Oxygen concentration in abomasal fluid varied between 10 and 30 microM in both infected and uninfected animals. During infection, oxygen concentration decreased slightly with increased abomasal pH, though the correlation between the two was poor (r=-0.30). In conclusion, O. circumcincta can consume oxygen and oxygen concentration at the infection site is sufficient to support at least some aerobic metabolism.


Meniscal function and the importance of meniscal regeneration in preventing late medical compartment osteoarthrosis.
The medial meniscus was totally removed in 22 patients who were followed up for more than ten years. Preservation of the meniscal rims enhances regeneration. There was no evidence of medial compartment damage in 91% of the patients by arthroscopic examination at ten years' follow-up examination. This finding suggests that meniscal rim regeneration can protect the joint from osteoarthrotic changes. Late medial compartment osteoarthrosis following medial meniscectomy in an otherwise normal knee is probably avoidable if surgical and postoperative treatment are designed to enhance regeneration of the meniscal rim.


Stent-assisted coiling of ruptured wide-necked intracranial aneurysms: A single-center experience of 218 consecutive patients.
Stent-assisted coiling (SAC) in the treatment of ruptured intracranial aneurysms (RIAs) remains controversial. In this study, we report our experience of SAC of wide-necked RIAs and evaluate the risk factors contributing to periprocedural complications. 218 patients underwent SAC for ruptured, wide-necked saccular intracranial aneurysms at our center between 2011 and 2014. Multivariate logistic regression analysis was performed to evaluate the risk factors contributing to the periprocedural complications. Follow-up angiography was available in 178 (84.8%) patients. Clinical outcome was measured using the Glasgow Outcome Scale (GOS) through telephonic interviews. Periprocedural complications occurred in 33 (15.1%) patients out of which 17 were thromboembolic (7.8%) and the remainder were hemorrhagic complications (n = 16, 7.3%). Multivariate logistic regression analysis showed that a positive history of hypertension (odds ratio [OR] 4.899, 95% confidence interval [CI] 1.266-18.951; P = 0.021), and daughter blebs (OR 12.165, 95% CI 3.247-45.577; P = 0.0001) were the major risk factors for the periprocedural hemorrhagic complications, but not for the thromboembolic complications. Angiographic follow-up (mean, 19.5 ± 11.9 months) showed Raymond scale (RS) 1 in 158 (88.8%) patients and RS2 in 20 (11.2%) patients without any angiographic recurrence. At a mean clinical follow-up of 29.1 ± 16.2 months, 201 out of the 210 surviving patients had a good functional outcome (GOS score of 4 or 5). SAC is an effective treatment option for selected ruptured wide-necked aneurysms, especially in patients who do not require external ventricle drainage for acute hydrocephalus. The periprocedural hemorrhagic complications tend to be more common in the hypertensive patients and in those with daughter blebs in the aneurysm sac.


Affinity partitioning of albumin and alpha-fetoprotein in an aqueous two-phase system using poly(ethylene glycol)-bound triazine dyes.
Human albumin and alpha-fetoprotein are partitioned in an aqueous two-phase system composed of 10% (w/w) Dextran and 7.5% (w/w) poly(ethylene glycol). When a small amount of poly(ethylene glycol) is replaced by Cibacron Blue F3G-A-liganded poly(ethylene glycol) the partition coefficient, K, of albumin increases by the factor of about 4000 whereas the K value of alpha-fetoprotein undergoes only a small change. The change of the partition coefficient in a logarithmic scale induced by increasing dye-polymer concentrations turned out as a useful measure for the affinity of albumin and alpha-fetoprotein to the dyes. The effect of pH and salt concentration on the affinity partition of albumin and alpha-fetoprotein is demonstrated. The partition of the two proteins in presence of Cibacron Blue F3G-A-liganded poly(ethylene glycol) is compared with seven other triazine dye-poly(ethylene glycol) derivatives.


Saccharification of sunflower stalks using lignocellulases from a fungal consortium comprising Pholiota adiposa and Armillaria gemina.
Lignocellulases from Armillaria gemina and Pholiota adiposa are efficient in hydrolyzing aspen and poplar biomass, respectively. In the present study, lignocellulosic enzymes obtained from a fungal consortium comprising P. adiposa and A. gemina were used for the saccharification of sunflower stalks. Sunflower stalks were thermochemically pretreated using 2 % NaOH at 50 °C for 24 h. The saccharification process parameters including substrate concentration, enzyme loading, pH, and temperature were optimized using response surface methodology to improve the saccharification yield. The highest enzymatic hydrolysis (84.3 %) was obtained using the following conditions: enzyme loading 10 FPU/g-substrate, substrate 5.5 %, temperature 50 °C, and pH 4.5. The hydrolysis yield obtained using the enzymes from the fungal consortium was equivalent to that obtained using a mixture of commercial enzymes Celluclast and Novozyme β-glucosidase. Addition of up to 500 ppm of heavy metal ions (As, Cu, Fe, Mn, Ni, Pb, and Zn) during saccharification did not significantly affect the saccharification yield. Thus, the biomass grown for phytoremediation of heavy metals can be used for the production of reducing sugars followed by ethanol fermentation.


Preparation courses for medical clerkships and the final clinical internship in medical education - The Magdeburg Curriculum for Healthcare Competence.
Supporting medical students entering their internships - the clinical clerkship and the internship "final clinical year" (Praktisches Jahr, PJ) - the seminars "Ready for Clerkship" and "Ready for PJ" were held for the first time in 2014 and continued successfully in 2015. These seminars are part of the "Magdeburg Curriculum for Healthcare Competence" (Magdeburger Curriculum zur Versorgungskompetenz, MCV). The concept comprises three main issues: "Understanding interdisciplinary clinical procedures", "Interprofessional collaboration", and "Individual cases and their reference to the system." The aim of the seminar series is to prepare students as medical trainees for their role in the practice-oriented clinical clerkship and PJ, respectively. Quality assurance evaluations and didactic research are integral parts of the seminars. In preparation for the "Ready for PJ" seminar a needs assessment was conducted. The seminars were rated by the participants using an anonymized questionnaire consisting of a 5-choice Likert scale (ranging from 1=fully agree to 5=fully disagree) and spaces for comments that was generated by the evaluation software Evasys. The results are presented for the preparatory seminars "Ready for Clerkship" and "Fit für PJ" held in 2014 and 2015. Overall, the students regarded the facultative courses as very good preparation for the clerkship as well as for the PJ. The three-dimensional main curricular concept of the MCV was recognized in the evaluation as a valuable educational approach. Interprofessional collaboration, taught by instructors focussing in teamwork between disciplines, was scored positively and highly valued. The "Magdeburg Curriculum for Healthcare Competence" (MCV) integrates clerkship and PJ in a framing educational concept and allows students a better appreciation of their role in patient care and the tasks that they will face. The MCV concept can be utilized in other practice-oriented phases (nursing internship, bed-side teaching, block internships).


Directional sensing during chemotaxis.
Cells have the innate ability to sense and move towards a variety of chemoattractants. We investigate the pathways by which cells sense and respond to chemoattractant gradients. We focus on the model system Dictyostelium and compare our understanding of chemotaxis in this system with recent advances made using neutrophils and other mammalian cell types, which share many molecular components and signaling pathways with Dictyostelium. This review also examines models that have been proposed to explain how cells are able to respond to small differences in ligand concentrations between the anterior leading edge and posterior of the cell. In addition, we highlight the overlapping functions of many signaling components in diverse processes beyond chemotaxis, including random cell motility and cell division.


Phenol-soluble modulins form amyloids in contact with multiple surface chemistries.
Functional amyloids are commonly produced by many microorganisms and their biological functions are numerous. Staphylococcus aureus can secrete a group of peptides named phenol-soluble modulins (PSMs) in their biofilm extracellular matrix. PSMs have been found inside biofilms both in their soluble form and assembled into amyloid structures. Yet, the actual biological function of these amyloids has been highly debated. Here, we assessed the ability of PSMs to form amyloids in contact with different abiotic surfaces to unravel a potential unknown bioadhesive and/or biofilm stabilization function. We combined surface plasmon resonance imaging, fluorescence aggregation kinetics, and FTIR spectroscopy in order to evaluate the PSM adsorption as well as amyloid formation properties in the presence of various surface chemistries. Overall, PSMs adsorb even on low-binding surfaces, making them highly adaptable adsorbants in the context of bioadhesion. Moreover, the PSM aggregation potential to form amyloid aggregates is not impacted by the presence of the surface chemistries tested. This versatility regarding adsorption and amyloid formation may imply a possible role of PSMs in biofilm adhesion and/or structure integrity.


Asymmetric synthesis and anti-HIV activity of L-carbocyclic 2',3'-didehydro-2',3'-dideoxyadenosine.
Asymmetric synthesis of L-carbocyclic 2',3'-didehydro-2',3'-dideoxyadenosine and its analogs were accomplished and their anti-HIV activities were evaluated. It was found that L-carbocyclic 2',3'-didehydro-2',3'-dideoxyadenosine exhibited moderately potent anti-HIV (EC50 = 2.4 microM) activity in human PBM cells without cytotoxicity up to 100 microM.


New properties of immunotropic preparation from porcine skin.
We studied new immunological and physicochemical properties of K-activin, immunotropic preparation from porcine skin isolated by the acetone method. The preparation restored the sensitivity of background rosette-forming cells in the spleen of thymectomized mice to the inhibitory effect of azathioprine in vivo and practically normalized serum thymic activity reduced in thymectomized mice. The molecular weight of proteins present in K-activin and previously detected by SDS-PAAG electrophoresis was determined by MALDI mass spectrometry


Acute effects of foam roller or stick massage on indirect markers from exercise-induced muscle damage in healthy individuals: A systematic review and meta-analysis.
This systematic review and meta-analysis examined the effects of foam roller or stick massage performed after exercise-induced muscle damage protocols on indirect markers of muscle damage compared to a non-intervention control group in healthy individuals. PubMed, Biblioteca Virtual em Saúde, Scopus, Google Scholar, and Cochrane Library database were searched in August 2, 2020, with last update on February 21, 2021. Were included clinical trials involving healthy adult individuals who received foam roller/stick massage versus a non-intervention group and evaluated indirect markers of muscle damage. Risk of bias was assessed by the Cochrane Risk of Bias tools. Standardized mean differences with 95% confidence intervals were used to measure the foam roller/stick massage effect on muscle soreness. The five included studies investigated 151 participants (136 men). Overall, the studies presented a moderate/high risk of bias. A between-groups meta-analysis showed no significant difference between massage and non-intervention control groups on muscle soreness immediately after (0.26 [95%CI: 0.14; 0.65], p = 0.20), 24 h (-0.64 [95%CI: 1.34; 0.07], p = 0.08), 48 h (-0.35 [95%CI: 0.85; 0.15], p = 0.17), 72 h (-0.40 [95%CI: 0.92; 0.12], p = 0.13), and 96 h (0.05 [95%CI: 0.40; 0.50], p = 0.82) after an exercise-induced muscle damage protocol. Moreover, the qualitative synthesis showed that foam roller or stick massage had no significant effect on range of motion, muscle swelling, and maximal voluntary isometric contraction recovery. In conclusion, the current literature appears to not support the advantage of foam roller or stick massage to improve recovery of muscle damage indirect markers (muscle soreness, range of motion, muscle swelling, and maximal voluntary isometric contraction) compared to a non-intervention control group in healthy individuals. Furthermore, due to the heterogeneity of the methodological designs among the included studies, making it difficult to compare the results. In addition, there are not enough high-quality and well-designed studies on foam roller or stick massage to draw any definite conclusions. The study was pre-registered in the International Prospective Register of Systematic Review (PROSPERO) on August 2, 2020, with last update on February 21, 2021. Protocol number: CRD2017058559.


Lima bean proteinase inhibitor. Origins of circular dichroism bands and modification by Br2- and (CNS)2-.
Origins of CD bands in lima bean proteinase inhibitor were deduced from an acetylation-deacetylation study of the sole tyrosyl residue in the protein (Tyr 69), and by analogy with Bowman-Birk soybean proteinase inhibitor, a homologous protein with similar spectral properties. Tyr 69 is relatively inaccessible to N-acetylimidazole; 100-fold molar excess of the reagent in the presence of 6 M guanidine hydrochloride elicited about 70 to 80% O-acetylation. A broad negative CD band centered around 280 nm arises mainly from the longest wavelength transition of cystinyl side chains (epsilon L--epsilon R approximately equal to -0.8 M-1 cm-1 per disulfide). The second cystinyl transition gives rise to a positive CD band of a comparable intensity at 247 nm. The Lb vibronic transition of Tyr 69 has negative CD around 280 nm, contributing approximately 10% of the total CD intensity at 278 nm (epsilon L--epsilon R approximately equal to -0.5 M-1 cm-1). The 232 nm positive shoulder is from the La vibronic transition of Tyr 69. Radical anions, Br2- and (CNS)2-, generated by the irradiation of N2O-saturated inhibitor solutions containing KBr or KCNS, reduced tyrosyl CD without affecting disulfide CD bands, indicating that the radical anions damaged Tyr 69 without altering protein conformation. The inhibitor modified at Tyr 69 by Br2- and (CNS)2- retained full activity toward trypsin and chymotrypsin. The irradiation of the inhibitor in the air-saturated solution led to loss in tyrosyl as well as cystinyl CD bands and decline in both antiproteinase activities.


Sex differences in forced-swim and open-field test behaviours after chronic administration of melatonin.
The effects of melatonin administered chronically on forced-swim test and open-field test behaviours were examined in male and female rats. The forced-swim test has been shown to be sensitive to all major classes of antidepressants and evidence indicates that melatonin possesses putative antidepressive properties. Male and female Long-Evans rats received either a regimen of chronic administration of melatonin or the control condition for 14 days via the drinking water. On day 15, each animal was individually introduced into a swim chamber, and was scored for 15 min on the duration of swimming, struggling, and immobility. After 24 h, each animal was again tested in the forced-swim test for 10 min. On day 18, all animals were tested in the open-field test apparatus for 5 min. Results revealed that females consistently showed higher activity levels than males in the forced-swim and open-field tests. Melatonin significantly increased struggling in males on day 15, but failed to do so in females. Also, whereas melatonin-treated females showed higher levels of behavioural immobility during their first exposure to the forced-swim test, this effect was prevented upon a second exposure. In both males and females, melatonin decreased swimming in the forced-swim test while increasing open-field ambulatory behaviour. Therefore, it is unlikely that melatonin's mechanism of action is a general inhibitory effect on motor activity. Taken together, the results suggest that the effects of melatonin treatment on forced-swim test behaviours are sex- and test-dependent.


Editorial on "Diagnostic Efficacy of Contrast-Enhanced MRI in Detecting Residual or Recurrent Hepatocellular Carcinoma After Transarterial Chemoembolization: A Systematic Review and Meta-analysis".
5 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;52:1029-1030.


The Evaluation and Management of Suspicious Gastric Lesions Following Bariatric Surgery.
Obesity has reached epidemic proportions worldwide and is associated with a higher mortality from several diseases, including adenocarcinoma of the esophagus and of the gastric cardia. Increased body mass index is associated with an increased incidence of gastroesophageal reflux disease (GERD), Barrett metaplasia, and adenocarcinoma of the cardia. Bariatric surgery remains the most effective therapy for morbid obesity and has the potential to improve weight-related GERD. A high index of suspicion is paramount for early detection of foregut neoplasia after bariatric surgery.


Opinion Mining for Educational Video Lectures.
The search for relevant educational videos is a time consuming process for the users. Furthermore, the increasing demand for educational videos intensifies the problem and calls for the users to utilize whichever information is offered by the hosting web pages, and choose the most appropriate one. This research focuses on the classification of user views, based on the comments on educational videos, into positive or negative ones. The aim is to give users a picture of the positive and negative comments that have been recorded, so as to provide a qualitative view of the final selection at their disposal. The present paper's innovation is the automatic identification of the most important words of the verbal content of the video lectures and the filtering of the comments based on them, thus limiting the comments to the ones that have a substantial semantic connection with the video content.


Polyp of the fallopian tube.
The case of a 34-year-old woman who had a radical hysterectomy for stage 1 b squamous cell carcinoma of the cervix and in whom an epithelial polyp was identified in the left fallopian tube is presented. The case is unusual in that the polyp developed in the absence of any evidence of tubal damage as demonstrated by a history of endometriosis or tubal sterilisation.


Supersensitivity of spinal opioid receptors to antagonists in intrathecal butorphanol and morphine dependence.
The purpose of this investigation was to evaluate changes in the sensitivity of spinal opioid receptors to selective antagonists in rats rendered dependent on intrathecal (i.t.) butorphanol and morphine. Using quantitative autoradiography, competitive binding assays with selective opioid antagonists were performed in the spinal cord sections of i.t. butorphanol- and morphine-dependent rats in which withdrawal was precipitated by i.t. naloxone. In butorphanol-dependent rats, the spinal kappa-opioid receptor developed a greater degree of antagonist supersensitivity than the spinal delta- and mu-opioid receptors did. In contrast, the spinal mu-opioid receptor became more sensitive than the delta-opioid receptor in morphine-dependent rats. These results indicate that differential supersensitivity of spinal opioid receptors was induced after chronic i.t. infusions of butorphanol and morphine.


A Rare Pediatric Example of Subcutaneous Extraskeletal Osteosarcoma: A Case Report and Review of the Morphologic Differential Diagnosis.
Primary extraskeletal osteosarcoma is an exceedingly rare malignant neoplasm that accounts for approximately 1% of soft tissue sarcomas and most often occurs in the deep soft tissues of adults. Extraskeletal osteosarcoma is characterized by the production of osteoid, bone, and/or chondroid matrix. The diagnosis of extraskeletal osteosarcoma requires careful radiologic and clinical correlation to ensure that the patient does not have an underlying bone primary. This is a case report of primary subcutaneous extraskeletal osteosarcoma arising in the thigh of a 15-year-old girl with a complex karyotype, and the morphologic differential diagnosis is reviewed.


Pax5: a master regulator of B cell development and leukemogenesis.
The B cell lineage of the hematopoietic system is responsible for the generation of high-affinity antibodies, which provide humoral immunity for protection against foreign pathogens. B cell commitment and development depend on many transcription factors including Pax5. Here, we review the different functions of Pax5 in regulating various aspects of B lymphopoiesis. At B cell commitment, Pax5 restricts the developmental potential of lymphoid progenitors to the B cell pathway by repressing B-lineage-inappropriate genes, while it simultaneously promotes B cell development by activating B-lymphoid-specific genes. Pax5 thereby controls gene transcription by recruiting chromatin-remodeling, histone-modifying, and basal transcription factor complexes to its target genes. Moreover, Pax5 contributes to the diversity of the antibody repertoire by controlling V(H)-DJ(H) recombination by inducing contraction of the immunoglobulin heavy-chain locus in pro-B cells, which is likely mediated by PAIR elements in the 5' region of the V(H) gene cluster. Importantly, all mature B cell types depend on Pax5 for their differentiation and function. Pax5 thus controls the identity of B lymphocytes throughout B cell development. Consequently, conditional loss of Pax5 allows mature B cells from peripheral lymphoid organs to develop into functional T cells in the thymus via dedifferentiation to uncommitted progenitors in the bone marrow. Pax5 has also been implicated in human B cell malignancies because it can function as a haploinsufficient tumor suppressor or oncogenic translocation fusion protein in B cell precursor acute lymphoblastic leukemia.


Using a bank of predatory fish samples for bioindication of radioactive contamination of aquatic food chains in the area affected by the Chernobyl accident.
From the analysis of experimental data on radioactive contamination of various fish, it is suggested that predatory fish specimens can be used as bioindicators of radionuclide accumulation in reservoir food chains of the Chernobyl emergency area. The increased content of cesium radionuclides were detected in the muscle tissue of predatory fish collected in various regions of the Chernobyl emergency area. In most of the water bodies studied, maximum contamination levels of predatory fish by radionuclides of cesium occurred in 1987-1988, whereas in 'nonpredatory' fish the concentration of cesium was maximum, as a rule, in the first year following the accident. The exposure doses of fish of various ecological groups and ages are estimated. The exposure doses of various population groups, using fish from contaminated water bodies, are also estimated. When forming the environmental data bank for the Chernobyl accident zone it is suggested that perch, pike-perch and pike be used as bioindicators of radioactive contamination of food chains.


iNOS Gene Ablation Prevents Liver Fibrosis in Leptin-Deficient ob/ob Mice.
iNOS deficiency in ob/ob mice improved liver inflammation and ECM remodeling-related genes, decreasing fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in hepatocytes, suggesting an important role of this alarmin in the development of NAFLD.


Quantitative single photon emission computed tomography derived standardized uptake values on 99mTc-PYP scan in patients with suspected ATTR cardiac amyloidosis.
Technetium-99 pyrophosphate scintigraphy (99mTc-PYP) provides qualitative and semiquantitative diagnosis of ATTR cardiac amyloidosis (ATTR-CA) using the Perugini scoring system and heart/contralateral heart ratio (H/CL) on planar imaging. Standardized uptake values (SUV) with quantitative single photon emission computed tomography (xSPECT/CT) can offer superior diagnostic accuracy and quantification through precise myocardial contouring that enhances assessment of ATTR-CA burden. We examined the correlation of xSPECT/CT SUVs with Perugini score and H/CL ratio. We also assessed SUV correlation with cardiac magnetic resonance (CMR), echocardiographic, and baseline clinical characteristics. Retrospective review of 78 patients with suspected ATTR-CA that underwent 99mTc-PYP scintigraphy with xSPECT/CT. Patients were grouped off Perugini score (Grade 0-1 and Grade 2-3), H/CL ratio (≥ 1.5 and < 1.5). Two cohorts were also created: myocardium SUVmax > 1.88 and ≤ 1.88 at 1-hour based off an AUC curve with 1.88 showing the greatest sensitivity and specificity. Cardiac SUV retention index was calculated as [SUVmax myocardium/SUVmax vertebrae] × SUVmax paraspinal muscle. Primary outcome was myocardium SUVmax at 1-hour correlation with Perugini grades, H/CL ratio, CMR, and echocardiographic data. Higher Perugini Grades corresponded with higher myocardium SUVmax values, especially when comparing Perugini Grade 3 to Grade 2 and 1 (3.03 ± 2.1 vs 0.59 ± 0.97 and 0.09 ± 0.2, P < 0.001). Additionally, patients with H/CL ≥ 1.5 had significantly higher myocardium SUVmax compared to patients with H/CL ≤ 1.5 (2.92 ± 2.18 vs 0.35 ± 0.60, P < 0.01). Myocardium SUVmax at 1-hour strongly correlated with ECV (r = 0.91, P = 0.001), pre-contrast T1 map values (r = 0.66, P = 0.037), and left ventricle mass index (r = 0.80, P = 0.002) on CMR. SUVs derived from 99mTc-PYP scintigraphy with xSPECT/CT provides a discriminatory and quantitative method to diagnose and assess ATTR-CA burden. These findings strongly correlate with CMR.


Substrate- and product-affinity resins for adenosine deaminase obtained by immobilisation of adenosine and inosine via 2',3'-cyclic acetal derivatives.
Immobilised inosine (6a) and adenosine (6c) and their 5'-phosphates have been synthesized. Reaction of the nucleosides with ethyl levulinate, followed by saponification or phosphorylation and then saponification, gave the 2',3'-O-[1-(2-carboxyethyl)ethylidene] derivatives 3 and 4 and the corresponding 5'-phosphates 2b and 2d. 6-Aminohexylagarose (5) was severally coupled to 2b, 2d, 3, and 4 through the carboxyl groups to give the polymers 6a-d. Adenosine deaminase converts 3 into 4, and 6c into 6a. The polymers can be used as affinity resins for adenosine deaminase, which is bound more strongly to 6c than to 6a. The operational capacity of 6a for adenosine deaminase is constant at 15--25 degrees, but decreases by approximately 16% from 25 degrees to 35 degrees. The resin 6a has been used to separate adenosine deaminase from mixtures containing other enzymes, for example, guanase or alcohol dehydrogenase.


Peroxisomal acyl-CoA synthetases.
Peroxisomes carry out many essential lipid metabolic functions. Nearly all of these functions require that an acyl group-either a fatty acid or the acyl side chain of a steroid derivative-be thioesterified to coenzyme A (CoA) for subsequent reactions to proceed. This thioesterification, or "activation", reaction, catalyzed by enzymes belonging to the acyl-CoA synthetase family, is thus central to cellular lipid metabolism. However, despite our rather thorough understanding of peroxisomal metabolic pathways, surprisingly little is known about the specific peroxisomal acyl-CoA synthetases that participate in these pathways. Of the 26 acyl-CoA synthetases encoded by the human and mouse genomes, only a few have been reported to be peroxisomal, including ACSL4, SLC27A2, and SLC27A4. In this review, we briefly describe the primary peroxisomal lipid metabolic pathways in which fatty acyl-CoAs participate. Then, we examine the evidence for presence and functions of acyl-CoA synthetases in peroxisomes, much of which was obtained before the existence of multiple acyl-CoA synthetase isoenzymes was known. Finally, we discuss the role(s) of peroxisome-specific acyl-CoA synthetase isoforms in lipid metabolism.


TBET-based ratiometric fluorescent probe for Hg2+ with large pseudo-Stokes shift and emission shift in aqueous media and intracellular colorimetric imaging in live Hela cells.
The detection of Hg2+ in biological systems and its imaging is of highly importance. In this work, a novel ratiometric fluorescence probe is developed based on through-bond energy transfer (TBET) with a 2-(2-hydroxyphenyl)benzoxazole (HBO) as donor and a Rhodamine derivative-Hg conjugate (RDM-Hg) as acceptor. Hg2+ weakens the fluorescence of HBO at 430 nm and meanwhile interacts with Rhodamine B derivative to form a fluorescent conjugate (RDM-Hg) giving rise to emission at 597 nm with a 167 nm red-shift. Further, the difference 282 nm between the donor absorption (315 nm) and the accepter emission (597 nm) for 1+Hg2+ is comparable to the highest value of the Stokes shift (282 nm) reported earlier for other reported TBET-based cassette. Through-bond energy transfer from HBO to RDM-Hg is triggered by Hg2+ resulting in concentration-dependent variation of fluorescence ratio I597/I430. A linear calibration of I597/I430versus Hg2+ concentration is obtained within 0-5 μM, along with the lowest detection limit being found to be as low as 1.31 × 10-9 mol·L-1 (~ 0.26 ppb) for Hg2+. This feature is further demonstrated by colorimetric imaging of test strip and intracellular Hg2+. On the other hand, the HBO/RDM TBET sensing system is characterized by a combination of high sensitivity and selectivity. The present study provides an approach for further development of ratiometric probes dedicated to selective in vitro or in vivo sensing some species of biologically interest.


[An unusual case of condylomata acuminata identified in the nasal cavity of a patient living in Yaoundé, Cameroon: a clinical report and literature review].
Condylomata acuminata are sexually transmitted lesions caused by human papillomavirus. They mainly occur in the anogenital area and exceptionally in the nasal cavity. We here report a new case of uncommon detection. The study involved a HIV-positive female patient with recurrence of vulvar condylomata acuminata treated in the department of gynecology. She was referred to our department with pink masses in the nasal cavity preventing nasal breathing and evolving over several weeks. Clinical examination and computerized tomography (CT) scan suggested condylomata. Surgical treatment was performed under general anesthesia and endoscopic control; the histological examination showed condylomata acuminata. The postoperative course was simple, with no recurrence after 6 months of follow-up. Condylomata acuminata in the nasal cavity are rare or even exceptional; only very few cases have been described in the literature. They commonly affect young subjects with or without HIV infection, having sexual risk behavior and can occur in several areas, in particular in the genital area. In this case, nasal lesions could result from hand-mediated transfer. Surgical treatment is effective and long-term follow-up is essential to treat possible recurrences.


Immune profile of primary and recurrent epithelial ovarian cancer cases indicates immune suppression, a major cause of progression and relapse of ovarian cancer.
Ovarian cancer is the third most prevalent cancer in Indian women. Relative frequency of High grade serous epithelial ovarian cancer (HGSOC) and its associated deaths are highest in India which suggests the importance of understanding their immune profiles for better treatment modality. Hence, the present study investigated the NK cell receptor expression, their cognate ligands, serum cytokines, and soluble ligands in primary and recurrent HGSOC patients. We have used multicolor flow cytometry for immunophenotyping of tumor infiltrated and circulatory lymphocytes. Procartaplex, and ELISA were used to measure soluble ligands and cytokines of HGSOC patients. Among the enrolled 51 EOC patients, 33 were primary high grade serous epithelial ovarian cancer (pEOC) and 18 were recurrent epithelial ovarian cancer (rEOC) patients. Blood samples from 46 age matched healthy controls (HC) were used for comparative analysis. Results revealed, frequency of circulatory CD56Bright NK, CD56Dim NK, NKT-like, and T cells was reduced with activating receptors while alterations in immune subsets with inhibitory receptors were observed in both groups. Study also highlights differential immune profile of primary and recurrent ovarian cancer patients. We have found increased soluble MICA which might have acted as "decoy" molecule and could be a reason of decrease in NKG2D positive subsets in both groups of patients. Furthermore, elevated level of serum cytokines IL-2, IL-5, IL-6, IL-10, and TNF-α in ovarian cancer patients, might be associated with ovarian cancer progression. Profiling of tumor infiltrated immune cells revealed the reduced level of DNAM-1 positive NK and T cells in both groups than their circulatory counterpart, which might have led to decrease in NK cell's ability of synapse formation. The study brings out differential receptor expression profile on CD56BrightNK, CD56DimNK, NKT-like, and T cells, cytokines levels and soluble ligands which may be exploited to develop alternate therapeutic approaches for HGSOC patients. Further, few differences in the circulatory immune profiles between pEOC and rEOC cases, indicates the immune signature of pEOC undergoes some changes in circulation that might facilitated the disease relapse. They also maintains some common immune signatures such as reduced expression of NKG2D, high level of MICA as well as IL-6, IL10 and TNF-α, which indicates irreversible immune suppression of ovarian cancer patients. It is also emphasized that a restoration of cytokines level, NKG2D and DNAM-1on tumor infiltrated immune cells may be targeted to develop specific therapeutic approaches for high-grade serous epithelial ovarian cancer.


Migration and transformation mechanism of phosphorus in waste activated sludge during anaerobic fermentation and hydrothermal conversion.
This study investigated migration and transformation mechanism of P in waste activated sludge (WAS) during anaerobic fermentation (AF) process and the subsequent hydrothermal conversion (HTC) process. Control of pH during the AF processes was found to be significant, whereby the use of acidic (pH = 5.5) or alkaline conditions (pH = 9.5) facilitated the release of either apatite phosphorus (AP) or non-apatite inorganic phosphorus (NAIP) and organic phosphorus, respectively. At the same pH of 9.5, NaOH promoted the transfer of P into liquid phase, and P in the solid phase was mainly in the form of NAIP. In contrast, Ca(OH)2 enhanced the incorporation of P into the solid products, with the P mainly in the form of AP. The subsequent HTC process promoted the NAIP transferred to AP, and the bioavailability of P in the HTC solid products was decreased. The P K-edge X-ray absorption near edge structure analysis provided detailed information about the phosphates. It demonstrated that the conversion of Ca8H2PO4·6.5H2O to Ca5(PO4)3·OH was facilitated by HTC under the alkaline condition. This study sheds lights on transformation mechanism of P speciations during AF and HTC processes, which would provide fundamental information for effective utilization of P in bio-wastes.


Discrete and ultradiscrete models for biological rhythms comprising a simple negative feedback loop.
Many biological rhythms are generated by negative feedback regulation. Griffith (1968) proved that a negative feedback model with two variables expressed by ordinary differential equations do not generate self-sustained oscillations. Kurosawa et al. (2002) expanded Griffith׳s result to the general type of negative feedback model with two variables. In this paper, we propose discrete and ultradiscrete feedback models with two variables that exhibit self-sustained oscillations. To obtain the model, we applied tropical discretization and ultradiscretization to a continuous model with two variables and then investigated its bifurcation structures and the conditions of parameters for oscillations. We found that when the degradation rate of the variables is lower than their synthesis rate, the proposed models generate oscillations by Neimark-Sacker bifurcation. We further demonstrate that the ultradiscrete model can be reduced to a Boolean system under some conditions.


Reduced protein availability by albumen removal during chicken embryogenesis decreases body weight and induces hormonal changes.
What is the central question of this study? Prenatal protein undernutrition by albumen removal in an avian model of fetal programming leads to long-term programming effects, but when do these effects first appear and are these programming effects regulated by the same candidate genes as in mammals? What is the main finding and its importance? The present results indicate that prenatal protein undernutrition by albumen removal induces phenotypical and hormonal changes in the early posthatch period, when the mismatch between the prenatal and postnatal environment first arises, but these changes are not accompanied by an altered gene expression of the selected candidate genes. Studies of the chicken offer a unique model for investigation of the direct effects of reduced prenatal protein availability by the partial replacement of albumen with saline in eggs at embryonic day 1 (albumen-deprived group). The results were compared with mock-treated sham chicks and non-treated control chicks. Although no differences in hatch weight were found, body weight and growth were reduced in the albumen-deprived chicks until 3 weeks of age. The feed intake of the albumen-deprived chicks, however, was increased compared with the control (day 13-21) and the sham chicks (day 16-18). In the albumen-deprived chicks, the ratio of thyroxine to 3,5,3'-triiodothyronine in the plasma was increased compared with the control chicks, whereas the plasma corticosterone level was increased only at day 7 compared with both other groups. The plasma glucose concentration and glucose tolerance were not affected by treatment. Several candidate genes previously associated with effects of prenatal protein deprivation in mammals were examined in the liver of newly hatched chicks. Gene expression of glycogen synthase 2, glycogen phosphorylase 1, peroxisome proliferator-activated receptor α and γ and glucocorticoid receptor was not affected by the treatment. In conclusion, reduction of prenatal protein availability led to differences in body weight and influenced hormones involved in metabolism and growth. Gene expression of the selected candidate genes was not altered, in contrast to mammals.


Adapting home telehealth group appointment model (CoYoT1 clinic) for a low SES, publicly insured, minority young adult population with type 1 diabetes.
As more individuals from diverse backgrounds are diagnosed with Type 1 Diabetes (T1D), the need to address resulting disparities in diabetes outcomes among these populations also escalates. Although young adulthood proves challenging for all patients with diabetes, young adults (YA) from racial/ethnic minorities and low socioeconomic backgrounds face even greater T1D management obstacles. The poorer outcomes in these populations drive an urgent need for alternative care models to improve YA's engagement in their T1D clinical care and address barriers to improved health outcomes. Previous telemedicine initiatives for T1D have yielded positive diabetes care results, especially in YA, offering one promising way to reach this high-risk population. To serve these patients better, an established and successful home telehealth group appointment model, "CoYoT1 Clinic" (Colorado Young Adults with T1D), was adapted to provide care to YA with T1D at a large urban children's hospital in Southern California. At this location, ~70% of patients have public/no insurance, and 85% are racial/ethnic minorities. In this paper, we report the process of adapting the CoYoT1 Clinic model and designing a randomized controlled trial (RCT) to evaluate its efficacy. The adapted model uses meticulous study-design methods that incorporate patient advisors, quantitative and qualitative data collection, collaboration with local stakeholders, intervention development, and patient randomization into a factorial design analyzing telemedicine versus in-person and patient-centered versus standard care. The new model addresses the needs of high-risk YA in Southern California, with the goal of increasing access to care, improving follow-up frequency, and strengthening patient and provider satisfaction. The study is registered with ClinicalTrials.gov (Clinical Trials Number: NCT03793673).


New antiviral agents for dermatologic disease.
The topic of antiviral agents for dermatologic disease is an area that is rapidly changing and expanding as our knowledge of herpes viruses, HIV, and human papilloma viruses continues to expand. New drugs are continuing to make therapy for these viruses more efficacious day by day. This review will discuss the recent advances in antiviral therapy, new therapies currently being developed or studied, and the future of antiviral vaccines.


Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infection.
Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury. To investigate whether acid suppression treatment after eradication influences the development of gastric erosions. Eighty-one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2-blocker for 6 months (H2-blocker-positive) and 41 received no treatment (H2-blocker-negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication. Cumulative prevalence of gastric erosions in the H2-blocker-positive group was significantly lower than in the H2-blocker-negative group, 25% vs. 42%, respectively. In the H2-blocker-negative group but not the H2-blocker-positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis. Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication.


The effects of impulse noise on the eardrum and middle ear.
Noise rarely damages the tympanic membrane and middle ear. High intensity impulse noise (explosions) can rupture the eardrum and disrupt the ossicular chain. Middle ear muscles play no part in the defense of the inner ear against high intensity impulse noise. Other mechanisms that protect the inner ear are slippage of the incudomalleal joint, a maximal limit of stapes displacement, and unlinking of the ossicular chain.


High-resolution NMR imaging of objects with dipolar-broadened spectra.
It is shown that, in some substances with dipolar-broadened conventional NMR spectra, it is possible to use long-lived coherent response signals, excited by long and weak radiofrequency pulses, for producing NMR images with high spatial resolution. Compared to other techniques, the method does not require high field gradients or strong radiofrequency fields, and therefore, can be applied to large objects.


Induction of tolerance to DNCB-contact sensitivity in guinea pig fetuses.
1. Female guinea pigs made tolerant before pregnancy do not transfer tolerance to their offspring. This result favours the concept of cellular mechanism of tolerance. 2. Guinea pig fetuses become tolerant when exposed to the tolerogen in the last two weeks of pregnancy. This is due to active tolerization by the tolerogen passing the placental barrier. 3. Fetuses exposed to the antigen earlier did not develop tolerance. This is due to immunological immaturity rather than to insufficiently developed vascularization. No functional active depot of tolerogen is formed. 4. Guinea pigs become immunologically mature between the 54th and 61st day of fetal live.


The effects of patulin and patulin-cysteine mixtures on DNA synthesis and the frequency of sister-chromatid exchanges in human lymphocytes.
The effects of patulin and patulin-cysteine mixtures on DNA synthesis in human blood lymphocytes were measured by assaying incorporation of [3H]thymidine into cellular DNA. Patulin inhibited and patulin-cysteine mixtures stimulated the incorporation of [3H]thymidine into DNA. The inhibitory action of patulin diminished with time in culture. Patulin was found to be unstable in the culture medium. The sister-chromatid exchange (SCE) frequency was significantly elevated by intermediate concentrations (0 . 1-0 . 2 micrograms/ml culture) of the toxin. The cells are protected from the effect at low concentrations of the toxin. There may be excessive damage at higher concentrations but only the unaffected cells go into mitosis. Therefore an increased frequency of SCEs is detected only at intermediate concentrations, or, at higher concentrations, with early harvesting. Cysteine seems to potentiate the effect of patulin on SCE frequency.


No correlation between phaeochromocytoma catecholamine secretion and granule ultrastructure.
It is uncertain whether biochemical markers of catecholamine secretion in patients with phaeochromocytoma correlate with tumour ultrastructure granule morphology. Fifteen patients with an adrenal phaeochromocytoma (n=13) or paraganglioma (n=2) (three men, 12 women; age 17-79 years) were studied. Catecholamine secretion was estimated by measuring urinary levels of free noradrenaline, adrenaline and dopamine. The number and type of secretory granules were evaluated by two independent observers on electron micrographs (area analysed approximately 70 microm2). Large round or elongated medium-density granules were adrenaline-type granules, whereas electron-dense granules lying in a vacuole were of noradrenaline type. No correlation was found between noradrenaline output and the number or percentage of noradrenaline-type granules, although tumours with normal noradrenaline output had only a minority of this type of granule (less than 25 per cent). Adrenaline-type granules were predominant (77 per cent of 163 granules) in a tumour secreting only adrenaline, but the proportion of adrenaline-type granules in six tumours with normal adrenaline output varied significantly (range 7-89 per cent). It was not possible to evaluate the granule type associated with dopamine secretion because one tumour secreting 14900 nmol dopamine and 1570 nmol adrenaline daily had a predominance of noradrenaline-type granules (63 per cent of 132 granules) and two dopamine-secreting tumours (5500 and 4250 nmol per day respectively) had 93 and 13 per cent noradrenaline-type granules. The lack of correlation between hormone output and granularity suggests that other factors determine secretory patterns in these tumours.


Periodic limb movements in sleep are linked to decreased hippocampus and amygdala volumes in the population-based BiDirect Study.
Even though numerous studies indicate that sleep disorders are associated with altered brain morphology, MRI studies focusing on periodic limb movements in sleep (PLMS) are scarce. Our aim was to investigate the association of PLMS with global and regional gray matter volumes as well as white matter hyperintensity (WMH) volume. One hundred and eighty-nine subjects (57.0 ± 7.8 years, women: 50.5%) of the population-based BiDirect Study underwent a single-night polysomnography (PSG). Standard criteria of the American Academy of Sleep Medicine were applied to evaluate sleep characteristics and calculate the PLMS index (PLMSI). T1w and FLAIR images were acquired with cerebral MRI at 3 Tesla. Voxel-based morphometry was performed to determine the total gray matter volume as well as the volume of cortical segments and subcortical gray matter areas using SPM12 and CAT12. The WMH volume was quantified with the Brain Intensity AbNormality Classification Algorithm. The independent relationship between MRI markers and PLMSI was analyzed using multivariable linear regression with adjustment for age, sex, body mass index, intracranial volume, PSG scorer, PSG device, sleep apnea, and the use of antidepressants. PLMSI was not significantly related to global gray matter volume and WMH volume. However, significant inverse associations of the PLMSI with the volume of the hippocampus (left and right hemisphere) and left amygdala were observed. A significant relationship between a higher PLMSI and lower volumes of the hippocampus and amygdala was found among the participants of the BiDirect Study. Since these associations are based on exploratory analyses, further replications are required before drawing firm conclusions.


Combination of Bacillus and Low Fertigation Input Promoted the Growth and Productivity of Chinese Cabbage and Enriched Beneficial Rhizosphere Bacteria Lechevalieria.
Long-term overfertilization increases soil salinity and disease occurrence and reduces crop yield. Integrated application of microbial agents with low fertigation input might be a sustainable and cost-effective strategy. Herein, the promoting effects of Bacillus velezensis B006 on the growth of Chinese cabbage under different fertigation conditions in field trials were studied and the underlying mechanisms were revealed. In comparison with normal fertigation (water potential of -30 kPa and soluble N, P, K of 29.75, 8.26, 21.48 Kg hm-2) without B006 application, the combination of B. velezensis B006 and reduced fertigation input (-50 kPa and N, P, K of 11.75, 3.26, 6.48 Kg hm-2) promoted cabbage growth and root development, restrained the occurrence of soft rot disease, and improved the yield. High-performance liquid chromatography (HPLC) analyses indicated that B006 application promoted the production of indole-3-acetic acid and salicylic acid in cabbage roots, which are closely related to plant growth. Rhizosphere microbiota analyses indicated that the combination of low fertigation input and B006 application promoted the enrichment of Streptomyces, Lechevalieria, Promicromonospora, and Aeromicrobium and the abundance of Lechevalieria was positively correlated with the root length and vitality. This suggested that the integrated application of reduced fertigation and Bacillus is highly efficient to improve soil ecology and productivity and will benefit the sustainable development of crop cultivation in a cost-effective way.


Duodenum-preserving total pancreatic head resection without segment resection of the duodenum for chronic pancreatitis.
The purpose of this study was to describe a duodenum-preserving total pancreatic head resection procedure without segment resection of the duodenum for the treatment of chronic pancreatitis with an enlarged pancreatic head. Between January 1999 and December 2006, 35 patients with chronic pancreatitis were operated on by duodenum-preserving total pancreatic head resection procedure without segment resection of the duodenum. These patients were followed up to estimate the outcomes of the surgical procedure. The mortality of the surgical procedure was 0. The overall morbidity was 17%. One patient developed pancreatic fistula, three patients developed bile leakage, and no patient developed duodenal fistula. Twenty-one patients who suffered abdominal pain in preoperative stage obtained complete pain relief, the mean European Organization for Research and Treatment of Cancer QLQ-C30 pain scale decreased from 59 +/- 27 to 13 +/- 21. In the postoperative stage, the endocrine function of the patients compared equally to the preoperative stage. The modified procedure obtains acceptable postoperative outcomes and benefits on extirpation of inflammatory lesions and avoidance of the anastomosis of the residual pancreatic head and the jejunum.


Reliability of palpation of humeral head position in asymptomatic shoulders.
The purpose of this study was to determine if, within a normal population: (1) palpation of the humeral head, relative to the acromion, in three static positions, was a reliable technique (2) there was a difference in humeral head position between the dominant and non-dominant shoulders in the three positions (3) there was a difference in humeral head position relative to the acromion between the arm at side (AS), the 90 degrees abduction/external rotation (AER) and 90 degrees abduction/internal rotation (AIR) positions. This test-retest study recorded palpation landmarks using a standardized protocol. Intra-tester reliability was above 0.8 for both AS and AER and all other ICCs were below 0.6. There was no systematic difference between dominant and non-dominant sides in any of the three positions (AS P=0.408, AER P=0.448, AIR P=0.233). There was a significant difference in measurements between each position (P<0.001). It can be concluded that, palpation of humeral head position in relation to the acromion is a reliable technique in the AS position. These normative data provide a baseline that can be used for future comparison if differences are found to exist in subgroups with pathological shoulder conditions where larger glenohumeral translations are thought to exist.


Predictors of prolonged hospital stay for the treatment of severe neuropsychiatric symptoms in patients with dementia: a cohort study in multiple hospitals.
Long hospitalization is often needed to treat severe behavioral and psychological symptoms of dementia (BPSD), which places heavy demands on hospital resources. Consequently, patients with severe BPSD usually wait for a long time to be admitted. There is a need to identify factors related to long hospitalization to better manage resources of a psychiatric hospital. We surveyed 150 consecutive patients hospitalized in the neuropsychiatric units of three hospitals for treatment of BPSD from 11 May 2009 to 30 November 2010. Only patients with reliable relatives were included in the study. We evaluated data of the patients (demographics, cognitive impairment, activities of daily living, causal disease for dementia, dementia severity, and the amount of pension), their primary caregivers (demographics and care burden), and their doctors' years of experience in treating dementia. We followed up to 180 days and assessed the effect of these factors on the length of stay. Of the 150 patients, 104 were discharged within 180 days and 46 were hospitalized for more than 180 days. Average length of stay for patients was 110.4 ± 58.1 days. In both univariate and multivariate Cox proportional hazard analyses, length of stay was longer for patients with smaller pensions and patients whose doctors had fewer years of experience in treating dementia. Length of stay was not found to be associated with any of the other variables. Patients with smaller pensions and whose doctors had less experience in treating dementia tended to require longer hospitalization.


Determination of a potential quantitative measure of the state of the lung using lung ultrasound spectroscopy.
B-lines are ultrasound-imaging artifacts, which correlate with several lung-pathologies. However, their understanding and characterization is still largely incomplete. To further study B-lines, lung-phantoms were developed by trapping a layer of microbubbles in tissue-mimicking gel. To simulate the alveolar size reduction typical of various pathologies, 170 and 80 µm bubbles were used for phantom-type 1 and 2, respectively. A normal alveolar diameter is approximately 280 µm. A LA332 linear-array connected to the ULA-OP platform was used for imaging. Standard ultrasound (US) imaging at 4.5 MHz was performed. Subsequently, a multi-frequency approach was used where images were sequentially generated using orthogonal sub-bands centered at different frequencies (3, 4, 5, and 6 MHz). Results show that B-lines appear predominantly with phantom-type 2. Moreover, the multi-frequency approach revealed that the B-lines originate from a specific portion of the US spectrum. These results can give rise to significant clinical applications since, if further confirmed by extensive in-vivo studies, the native frequency of B-lines could provide a quantitative-measure of the state of the lung.


Microenvironment modulation by key regulators of RNA N6-methyladenosine modification in respiratory allergic diseases.
RNA N6-methyladenosine (m6A) regulators are considered post-transcriptional regulators that affect several biological functions, and their role in immunity, in particular, is emerging. However, the role of m6A regulators in respiratory allergic diseases remains unclear. Therefore, we aimed to investigate the role of key m6A regulators in mediating respiratory allergic diseases and immune microenvironment infiltration characteristics. We downloaded gene expression profiles of respiratory allergies from the Gene Expression Omnibus (GEO) database and we performed hierarchical clustering, difference analysis, and construction of predictive models to identify hub m6A regulators that affect respiratory allergies. Next, we investigate the underlying biological mechanisms of key m6A regulators by performing PPI network analysis, functional enrichment analysis, and immune microenvironment infiltration analysis. In addition, we performed a drug sensitivity analysis on the key m6A regulator, hoping to be able to provide some implications for clinical medication. In this study, we identified four hub m6A regulators that affect the respiratory allergy and investigated the underlying biological mechanisms. In addition, studies on the characteristics of immune microenvironment infiltration revealed that the expression of METTL14, METTL16, and RBM15B correlated with the infiltration of the mast and Th2 cells in respiratory allergy, and METTL16 expression was found to be significantly negatively correlated with macrophages for the first time (R = -0.53, P < 0.01). Finally, a key m6A regulator, METTL14, was screened by combining multiple algorithms. In addition, by performing a drug sensitivity analysis on METTL14, we hypothesized that it may play an important role in the improvement of allergic symptoms in the upper and lower airways with topical nasal glucocorticoids. Our findings suggest that m6A regulators, particularly METTL14, play a crucial role in the development of respiratory allergic diseases and the infiltration of immune cells. These results may provide insight into the mechanism of action of methylprednisolone in treating respiratory allergic diseases.


Molecular and in silico analyses of SYN III gene variants in autism spectrum disorder.
Defects in neurotransmission and synaptogenesis are noteworthy in the pathogenesis of ASD. Synapsin III (SYN III) is defined as a synaptic vesicle protein that plays an important role in synaptogenesis and regulation of neurotransmitter release and neurite outgrowth. Therefore, SYN III may associate with many neurodevelopmental diseases, including ASD. The aim of this study was to investigate whether the SYN III gene -631 C > G (rs133946) and -196 G > A (rs133945) polymorphisms are associated with susceptibility to ASD. SYN III variants and the risk of ASD were investigated in 26 healthy children and 24 ASD children. SYN III gene variants were genotyped by PCR-RFLP methods. The differences in genotype and allele frequencies between the ASD and control groups were calculated using the chi-square (χ2). We analysed the SYN III gene using web-based tools. Our results suggest that the presence of the AA genotype of the SYN III -196 G > A (rs133945) polymorphism affects the characteristics and development of ASD in children (p = 0.012). SYN III -631 C > G (rs133946) polymorphism was not associated with ASD (p = 0.524). We have shown the prediction of gene-gene interaction that SYN III is co-expressed with 17 genes, physical interaction with 3 genes, and co-localization with 12 genes. The importance of different genes (SYN I, II, III, GABRD, NOS1AP, GNAO1) for ASD pathogenesis was revealed by GO analysis. Considering the role of SYN III and related genes, especially in the synaptic vesicle pathway and neurotransmission, its effect on ASD can be further investigated.


Changes in glycaemic control of oral anti-diabetic medications assessed by continuous glucose monitors among patients with type 2 diabetes: a protocol of network meta-analysis.
Continuous glucose monitors (CGMs) can measure interstitial fluid glucose levels to provide comprehensive real-time glucose profile among people with type 2 diabetes. These can accurately detect glucose levels, hyperglycaemia and hypoglycaemia events compared with conventional self-monitoring. Increased application of CGMs provides a valuable opportunity to evaluate glucose control on oral anti-diabetic medications. This review will compare the efficacy and safety of oral anti-diabetic medications among patients with type 2 diabetes, evaluated by CGM. The following databases will be searched: Cochrane Library, PubMed, EMBASE, CINAHL, PsycINFO, Scopus and grey literature (ClinicalTrials.gov, PsycEXTRA, ProQuest Dissertations, Google Scholar and Theses Global) for the identification of studies. The review will include and summarise evidence from randomised clinical trials that use CGMs for blood glucose management in adults (aged ≥ 18 years), published in English between January 2000 and May 2021 without any restrictions of countries. Reference list of all selected articles will independently be screened to identify additional studies left out in the initial search. Primary outcomes will be HbA1c (≤ 7.0%), time spent with hypoglycaemia (< 70 mg/dl) or hyperglycaemia (≥ 180 mg/dl). Secondary outcomes will be change in weight, blood pressure and related comorbidities (cardiovascular mortality, heart failure events, myocardial infarction and stroke). Study selection, data extraction and quality assessment will be conducted independently by at least two reviewers. A third reviewer will determine and resolve discrepancies. At least two independent reviewers will cross-check data synthesis. The quality of evidence of the review will be assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Tool. The review is anticipated to provide up to date evidence for further studies and clinic practices regarding glycaemic control, hypoglycaemia, and hyperglycaemia issues. The results will be published in a peer-reviewed journal. PROSPERO CRD42020188399 .


Snap-II predicts severe intraventricular hemorrhage and chronic lung disease in the neonatal intensive care unit.
To determine whether the Score for Neonatal Acute Physiology, Version II (SNAP-II), improved prediction of severe (> or = grade III) intraventricular hemorrhage (IVH) and chronic lung disease (CLD) when compared to models using gestational age (GA) and traditional risk factors (e.g., Apgar score, small-for-gestational-age, sex, outborn status). We examined 4226 infants < or = 32 weeks' GA admitted to 17 Canadian neonatal intensive care units between 1996 and 1997. We compared prediction models for severe IVH and CLD, with and without SNAP-II. SNAP-II was a significant and independent predictor of severe IVH and CLD. Addition of SNAP-II to models using GA and traditional risk variables significantly (p<0.05) improved model prediction (AUC 0.8 for severe IVH; 0.83 for CLD). Models were well calibrated (p>0.05 for Hosmer-Lemeshow goodness of fit test). Addition of SNAP-II to models using GA and traditional risk factors significantly improves prediction of severe IVH and CLD.


Graphene Distributed Amplifiers: Generating Desirable Gain for Graphene Field-Effect Transistors.
Ever since its discovery, graphene bears great expectations in high frequency electronics due to its irreplaceably high carrier mobility. However, it has long been blamed for the weakness in generating gains, which seriously limits its pace of development. Distributed amplification, on the other hand, has successfully been used in conventional semiconductors to increase the amplifiers' gain-bandwidth product. In this paper, distributed amplification is first applied to graphene. Transmission lines phase-synchronize paralleled graphene field-effect transistors (GFETs), combining the gain of each stage in an additive manner. Simulations were based on fabricated GFETs whose fT ranged from 8.5 GHz to 10.5 GHz and fmax from 12 GHz to 14 GHz. A simulated four-stage graphene distributed amplifier achieved up to 4 dB gain and 3.5 GHz bandwidth, which could be realized with future IC processes. A PCB level graphene distributed amplifier was fabricated as a proof of circuit concept.


Clinical profile of aortoiliac occlusive disease and outcomes of aortobifemoral bypass in India.
Aortoiliac arterial occlusive (AIOD) disease is common in India. The clinical presentation and etiology are different than in the West. Intervention is frequently required for advanced lower extremity ischemia, but the results have not been systemically evaluated. We studied the clinical profile and midterm results of patients undergoing aortobifemoral bypass for AIOD at a tertiary care center in south India. Clinical data of patients undergoing aortobifemoral bypass for AIOD over a 6-year period from January 1, 2005 to December 31, 2010 were retrospectively analyzed. Clinical presentation and factors affecting outcome were evaluated. Graft patency and mortality were included as study end points. Ninety-nine patients (mean age, 52 years) with AIOD who underwent aortobifemoral bypass were included. Etiology included atherosclerosis in 79 patients, thromboangiitis obliterans in 15, Takayasu's arteritis in two, and hematological conditions in 3. Smoking (82%), hypertension (40%), and diabetes (30%) were the most common risk factors; ischemic heart disease (4%), obesity (2%), and dyslipidemia (3%) were rare. Eighty-one percent of patients presented with critical limb ischemia. Mean duration of symptoms was 22 months (range, 4 months to 9 years). Concomitant infrainguinal arterial occlusive disease was identified in 81%, but intervened upon in only 2%. In-hospital mortality was 3%. Causes of death included myocardial infarction in two and colon ischemia in one. Major morbidity included nonfatal myocardial infarction (3%), pneumonia/atelectasis (5%), and renal dysfunction (2%). Groin wound complications occurred in 20%, seroma/lymph leak in 13%, infection in 7%, and anastomotic hemorrhage in 2%. Multidrug-resistant and polymicrobial infections were common. Early graft thrombosis (30 days) occurred in 15 patients; 8 of 11 reintervened grafts were salvaged. Four more grafts thrombosed during a mean follow-up of 2 years (range, 0-5 years) and two became infected. Overall study major limb loss rate was 10% (primary, 2%; secondary, 8%). Delayed presentation and smoking were more common in patients developing complications. There was no significant difference in overall complication rates between patients with thromboangiitis obliterans and atherosclerosis (P = .66). Despite earlier age at presentation, atherosclerosis remains the predominant etiology of aortoiliac arterial occlusive disease in Indian patients. Results of open revascularization are comparable to those in the Western literature. Thromboangiitis obliterans is the underlying pathology in a minority of patients with no significant difference in operative outcome. Patients frequently present late with critical limb ischemia, but this does not affect outcome.


Anatomical analysis of different helical plate designs for proximal humeral shaft fracture fixation.
Helical plates are preferably used for proximal humeral shaft fracture fixation and potentially avoid radial nerve irritation. Safety of applying four different long plate designs (straight, 45°-, 90°-helical and ALPS) with MIPO technique as well as assessment and comparison of their distances to adjacent anatomical structures. MIPO was performed in 16 human cadaveric humeri using either a straight (group 1), a 45°-helical (group 2), a 90°-helical (group 3) plate, or an ALPS (group 4). Applying CT angiography, distances between brachial arteries and plates were evaluated. All specimens were dissected and distances to the axillary, radial and musculocutaneous nerve were evaluated. No specimens demonstrated injuries of the anatomical structures at risk after MIPO with all investigated plate designs. Closest overall distance (mean (range); mm) between each plate and the radial nerve was 1 (1-3) in group 1, 7 (2-11) in group 2, 14 (7-25) in group 3 and 6 (3-8) in group 4. It was significantly bigger in group 3 and significantly smaller in group 1 compared to all other groups, p < 0.001. Closest overall distance between each plate and the musculocutaneous nerve was 16 (8-28) in group 1, 11 (7-18) in group 2, 3 (2-4) in group 3 and 6 (3-8) in group 4. It was significantly bigger in group 1 and significantly smaller in group 3 compared to all other groups, p < 0.001. MIPO with 45°- and 90°-helical plates as well as with ALPS is safely feasible and demonstrates significantly bigger distances to the radial nerve compared to straight plates. However, the distances remain small and attention must be paid to the musculocutaneous nerve and the brachial artery when MIPO is applied using ALPS, 45°- and 90°-helical implants.


Assessing the impact of enforcement and compliance with minimum staffing standards on the quality of care in nursing homes: Evidence from the Centers for Medicare and Medicaid Services' staff star rating downgrade policy.
Policymakers have historically attempted to influence quality in nursing homes through the imposition of minimum staffing standards and through the public dissemination of quality on websites like Care Compare. One current Federal standard necessitates a registered nurse (RN) on duty for at least eight consecutive hours each day. In 2018, the Centers for Medicare and Medicaid Services announced that they would incentivize compliance with this requirement by downgrading nursing homes with 7+ days without an RN present during the quarter by one star on their Care Compare staffing domain quality rating. This study evaluates the impact of this new enforcement mechanism. Using an intent-to-treat sample of nursing homes at risk for downgrade with difference-in-differences and event study models, it finds that the policy increased compliance and staffing levels. Using the policy to instrument for full compliance, it finds that the daily presence of an RN causally improves several quality dimensions.


Lymphovascular invasion, ureteral reimplantation and prior history of urothelial carcinoma are associated with poor prognosis after partial cystectomy for muscle-invasive bladder cancer with negative pelvic lymph nodes.
To identify predictive factors underlying recurrence and survival after partial cystectomy for pelvic lymph node-negative muscle-invasive bladder cancer (MIBC) (urothelial carcinoma) and to report the results of partial cystectomy among select patients. We retrospectively reviewed 101 cases that received partial cystectomy for MIBC (pT2-3N0M0) between 2000 and 2010. The log-rank test and a Cox regression analyses were performed to identify factors that were predictive of recurrence and survival. With a median follow-up of 53.0 months (range 9-120), the 5-year overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) rates were 58%, 65% and 50%, respectively. A total of 33 patients died of bladder cancer and 52 patients survived with intact bladder. Of the 101 patients included, 55 had no recurrence, 12 had non-muscle-invasive recurrence in the bladder that was treated successfully, and 34 had recurrence with advanced disease. The multivariate analysis showed that prior history of urothelial carcinoma (PH.UC) was associated with both CSS and RFS and weakly associated with OS; lymphovascular invasion (LVI) and ureteral reimplantation (UR) were associated with OS, CSS and RFS. Among patients with pelvic lymph node-negative MIBC, PH.UC and UR should be considered as contraindications for partial cystectomy, and LVI is predictive of poor outcomes after partial cystectomy. Highly selective partial cystectomy is a rational alternative to radical cystectomy for the treatment of MIBC with negative pelvic lymph nodes.


A comparative study of resource utilization in natural populations of Drosophila melanogaster and D. simulans.
Data were collected over four vintage seasons at the "Chateau Tahbilk" winery. The distribution of adults, larvae and pupae of D. melanogaster and D. simulans was recorded over a pile of grape residues during two different stages of its decomposition. Active fermentation characterized the first of these stages, but was much less apparent in the later stage. The distribution of adults was similar for both stages. However, while larvae and pupae of both species were observed in the post fermentation residues essentially only D. melanogaster larvae and pupae were present during the fermentation stage. During this stage larvae were aggregated beneath the surface to a depth of 10 cm. Here the average temperature was about 29°C and ethanol and acetic acid concentrations were around 7% (v/v) and 3% (v/v), respectively.Laboratory results allow a description of the physiological and behavioural responses of both species to ethanol or acetic acid concentration and to temperature differences. These results appear sufficient to explain the distribution of the species between and within the residue stages. However, before general statements of resource utilization or species interaction can be made, the need to study different stages of the life cycle is highlighted.


Limited diffusibility of gene products directed by a single nucleus in the cytoplasm of multinucleated myofibres.
Two types of beta-galactosidase genes, whose products are distributed in the nucleus (N beta-gal) or cytoplasm (C beta-gal), were injected with fructose intramuscularly into the quadriceps of adult mice. Regionally restricted and overlapped distributions of both gene products were observed in the myofibres. These findings indicate that N beta-gal is incorporated into the nucleus responsible for its synthesis and that C beta-gal becomes located in the vicinity of the nucleus after its synthesis. This restricted location of C beta-gal in myofibres remained unchanged during the development of infant mouse muscle. Thus, the gene products directed by the nucleus of myofibres seem to show limited diffusibility, suggesting a universal localization of subcellular domains in myofibres.


Intervention to reduce environmental tobacco smoke exposure in Latino children: null effects on hair biomarkers and parent reports.
To evaluate the effectiveness of a lay delivered intervention to reduce Latino children's exposure to environmental tobacco smoke (ETS). The a priori hypothesis was that children living in households that were in the intervention group would have lower exposure over time than measurement only controls. A two group, randomised control trial was conducted. Areas of San Diego county with a large Latino population. 143 Latino parent-child pairs. Trained bicultural and bilingual Latina lay community health advisors, or promotoras, conducted problem solving aimed at lowering the target child's exposure to ETS in the household. Six home and telephone sessions were delivered by the promotoras over a four month period. Outcome measures were collected at baseline, immediately post-intervention, three months post-intervention, and 12 months post-intervention. Four outcomes were considered: (1) parent's paper-and-pencil reports of the child's past month exposure; (2) hair samples from the child analysed for past month nicotine; (3) hair samples from the child analysed for past month cotinine; and (4) per cent confirmed reducers. There were no significant condition-by-time interactions, the term indicative of a differential intervention effect. Significant or near significant time main effects were seen for children's hair cotinine, per cent confirmed reducers, and, in particular, parent reports of exposure. Applying a lay promotora model to deliver the behavioural problem solving intervention unfortunately was not effective. A likely explanation relates to the difficulty of delivering a relatively complex intervention by lay women untrained in behaviour change theory and research methods.


Conversion of once-daily extended-release tacrolimus is safe in stable liver transplant recipients: A randomized prospective study.
Simplifying the therapeutic regimen of liver transplantation (LT) recipients may help prevent acute rejection and graft failure. The present study aimed to evaluate the efficacy and safety of conversion from twice-daily tacrolimus to once-daily extended-release tacrolimus under concurrent mycophenolate mofetil therapy in stable LT recipients. This randomized, prospective, controlled study included 91 patients who underwent LTs with at least 1 year of posttransplant follow-up. Conversion was made on a 1 mg to 1 mg basis. No incidences of biopsy-proven acute rejection, graft failure, or death were reported in either group at 24 weeks. Median serum tacrolimus level of the study group was 20% less than that of the control group at 8 weeks. However, no significant differences regarding biochemical indicators of liver function or serum creatinine levels were observed between the 2 groups. Adverse event (AE) profiles were similar for both groups, with comparable incidences of AEs and serious AEs. No significant differences regarding efficacy or safety were observed between the once-daily tacrolimus and twice-daily tacrolimus groups of stable LT recipients. In conclusion, our study suggests that tacrolimus can be safely converted from a twice-daily regimen to a once-daily regimen in stable LT recipients.


Escherichia coli Nissle 1917-driven microrobots for effective tumor targeted drug delivery and tumor regression.
Potent tumor regression remains challenging due to the lack of effective targeted drug delivery into deep tumors as well as the reduced susceptibility of cancer cells to anticancer agents in hypoxic environments. Bacteria-driven drug-delivery systems are promising carriers in overcoming targeting and diffusion limits that are inaccessible for conventional antitumor drugs. In this study, probiotic facultative anaerobe Escherichia coli Nissle 1917 (EcN) was functionalized and formed self-propelled microrobots to actively deliver therapeutic drug and photosensitizer to the deep hypoxic regions of tumors. Doxorubicin (Dox) was firstly modified with cis-aconityl anhydride (CA) and terminal thiol-decorated hydrazone derivative (Hyd-SH) through dual pH-sensitive amide and imine bonds, respectively. The functionalized CA-Dox-Hyd-SH was further coordinated with photosensitizer gold nanorods (AuNRs) and then conjugated to the surface of EcN. The resulting microrobots (EcN-Dox-Au) inherited the mobility characteristics and bioactivity of native EcN. Upon the irradiation of NIR laser, the microrobots exhibited enhanced tumor accumulation and penetration into the deep hypoxia tumor site. Strikingly, after 21 days of treatment with EcN-Dox-Au formulations, complete tumor regression was achieved without relapse for at least 53 days. This self-propelled strategy utilizing bacteria-driven microrobots provides a promising paradigm for enhancing drug penetration and elevating chemosensitivity, resulting in a superior antitumor effect. STATEMENT OF SIGNIFICANCE: Self-propelled Escherichia coli Nissle 1917 (EcN) - mediated microrobots are functionalized to co-deliver therapeutic drugs and photosensitizers to the deep tumor site. Anti-tumor drug doxorubicin (Dox) was modified through dual pH-sensitive bonds on both terminals and then linked with EcN and photosensitizer gold nanorods (AuNRs) to realize tumor microenvironment acidic pH-responsive drug release. Upon irradiation with a NIR laser near the tumor site, AuNRs produced a photothermal effect which realized the superficial tumor thermal ablation and increased the permeability of the tumor cell membrane to facilitate the penetration of microrobots. Moreover, the deep penetration of microrobots also enhanced the susceptibility of the cancer cells to Dox, and realized the complete tumor regression in the established breast cancer-bearing mice without recurrence using a lower dose of drug regimen.


[Mitotic activity of alveolar macrophages in nonspecific diffuse lung pathology].
Endopulmonary cytograms and mitotic activity of alveolar macrophages (AM) in the bronchoalveolar lavage (BAL) from 30 patients with diffuse lung pathology have been studied. AM mitosis was found in 24 cases. Mitotic index for all the patients was 0.65% and ranged from 0.25 to 2.75%. Electron microscopy revealed the capacity of differentiated forms of AM for mitotic division. Free AM may be regarded as slowly proliferating cell population, capable of self-reproduction in lung pathology.


Select cytoplasmic and membrane proteins increase the percentage of immobile integrins but do not affect the average diffusion coefficient of mobile integrins.
Integrins are ubiquitous adhesion receptors that are important for signaling and integrating the extracellular matrix and cytoskeleton. The role of cytoplasmic proteins vinculin, focal adhesion kinase (FAK), integrin-linked kinase (ILK), and membrane proteins epidermal growth factor receptor (EGFR) and Notch in altering αPS2CβPS integrin lateral diffusion was measured using single particle tracking (SPT) and RNA interference (RNAi). SPT measures heterogeneous diffusion properties, and RNAi selectively reduces the concentration of a target protein. After systematically reducing the concentration of vinculin, FAK, ILK, EGFR, or Notch, there was a 31 to 80% increase in the mobile integrin fraction, indicating that these five targeted proteins (or assemblies that contain these proteins) are responsible for immobilizing a fraction of the integrins when all proteins are present at native concentrations. The average diffusion coefficient of all mobile integrins did not change after any of the RNAi treatments, and the percentage of Brownian, directed, or anomalous/constrained trajectories relative to total mobile trajectories did not change after vinculin or EGFR RNAi. However, the fraction of anomalous/constrained trajectories relative to the total mobile trajectories increased 9 to 19% after FAK, ILK, and Notch RNAi, when the concentration of these proteins was reduced. In the case of FAK, ILK, and Notch, native concentrations of these proteins simultaneously increase the immobile fraction of integrins but decrease the diffusion constraints to those integrins that remain mobile. Comparisons of single receptor and ensemble measurements of diffusion and what is known about the effect of these proteins in altering integrin clustering are discussed.


Synthesis and structure-activity relationship studies on a novel series of naphthylidinoylureas as inhibitors of acyl-CoA:cholesterol O-acyltransferase (ACAT).
The synthesis and structure-activity relationships of N-phenyl-N'-[3-(4-phenylnaphthylidinoyl)]urea derivatives 3 as a novel structural class of potent ACAT inhibitors is described. A 3-methoxy group substituted on the naphthylidinone 4-phenyl ring, together with a 1-N-(n)butyl substitution, SM-32504 (3m), gave a potent ACAT inhibitor, in vitro, respectively. The most potent compound, SM-32504 (3m), decreased the serum cholesterol level significantly in a high fat and high cholesterol-fed mouse model.


Sex-role orientation: effect on self-esteem, need achievement and internality in college females.
This study investigated the effect of sex-role orientation on self-esteem, n Achievement, and internality in 98 college females. Specifically it was predicted that (a) college females possessing a non-traditional sex-role orientation would score higher in n Achievement than those possessing a traditional sex-role orientation; (b) no statistical difference would exist in the self-esteem scores of the two groups; and (c) the strength of the relationship between self-esteem and internality would vary for "non-traditional" (r = .41) and "traditional" females (r = .11). All three hypotheses received support from data of 98 undergraduates.


Carbazolothiophene-2-carboxylic acid derivatives as endothelin receptor antagonists.
The SmI(2)-promoted three-component coupling reaction of thiophene-2-carboxylate, indole-2-carbaldehyde and acetophenone provides an expedient route to a series of tetracyclic carbazolothiophene compounds bearing the indole and thiophene rings. Among these samples, 9-benzyl-4-methyl-4-(4-hydroxyphenyl)-10-oxo-4,10-dihydrocarbazolo[2,3-b]thiophene-2-carboxylic acid (18) shows the most potent inhibition against the endothelin-1 induced increase of intracellular calcium ion concentration.


Who thrives as a direct support professional? Personal motivation and resilience in direct support.
Direct support professionals (DSPs) are an essential part of the lives of people with intellectual and developmental disabilities (IDD). High rates of DSP turnover and vacancy have spurred much research into the occupational stress and burnout experienced by DSPs. There are, however, DSPs who remain motivated by and successful in the profession. Less research has been done on what makes these DSPs resilient to the same stressors that negatively affect other DSPs. The present study used the tenets of sensitivity theory to examine the relationships between motivation and outcome measures relevant to DSP success, namely vocational strain, depersonalization, and personal accomplishment. The motive of family related positively and vengeance related negatively with the three outcome variables. To a lesser extent, citizenship and social contact were positively related and prestige was negatively correlated with outcomes. The relevance of these findings and their potential applications to DSP recruitment and training are discussed.


Impact of pesticide coexposure: an experimental study with binary mixtures of lambda-cyhalothrin (LCT) and captan and its impact on the toxicokinetics of LCT biomarkers of exposure.
This study aimed at gaining more insights into the impact of pesticide coexposure on the toxicokinetics of biomarkers of exposure. This was done by conducting an in vivo experimental case-study with binary mixtures of lambda-cyhalothrin (LCT) and captan and by assessing its impact on the kinetic profiles of LCT biomarkers of exposure. Groups of male Sprague-Dawley rats were exposed orally by gavage to LCT alone (2.5 or 12.5 mg/kg bw) or to a binary mixture of LCT and captan (2.5/2.5 or 2.5/12.5 or 12.5/12.5 mg/kg bw). In order to establish the temporal profiles of the main metabolites of LCT, serial blood samples were taken, and excreta (urine and feces) were collected at predetermined intervals up to 48 h post-dosing. Major LCT metabolites were quantified in these matrices: 3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropane carboxylic (CFMP), 3-phenoxybenzoic acid (3-PBA), 4-hydroxy-3-phenoxybenzoic acid (4-OH3PBA). There was no clear effect of coexposure at the low LCT dose on the kinetics of CFMP and 3-PBA metabolites, based on the combined assessment of temporal profiles of these metabolites in plasma, urine and feces; however, plasma levels of 3-PBA were diminished in the coexposed high-dose groups. A significant effect of coexposure on the urinary excretion of 4-OH3PBA was also observed while fecal excretion was not affected. The temporal profiles of metabolites in plasma and in excreta were further influenced by the LCT dose. In addition, the study revealed kinetic differences between metabolites with a faster elimination of 3-PBA and 4-OH3BPA compared to CFMP. These results suggest that the pyrethroid metabolites CFMP and 3-PBA, mostly measured in biomonitoring studies, remain useful as biomarkers of exposure in mixtures, when pesticide exposure levels are below the reference values. However, the trend of coexposure effect observed in the benzyl metabolite pathway (in particular 4-OH3BPA) prompts further investigation.


Thermodynamics of peptide bond formation at clay mineral surfaces.
The possibility of surface catalysed condensation of unsubstituted amino acids on kaolinite in aqueous systems at elevated temperatures was investigated; no evidence of clay catalysed polycondensation has been found. The thermodynamic feasibility of the hypothetical lysine/dilysine condensation reaction in the temperature-range up to 90 degrees C was evaluated for a range of experimental conditions by the combination of measured free energies of lysine/dilysine cation exchange on kaolinite and on montmorillonite, and free energies for the analogous condensation reaction in homogeneous solution. The results indicate that, in spite of the high selectivity of the clays for the adsorption of cation dimers from dilute solutions, the thermodynamic barrier to the surface condensation of unsubstituted amino acids on clay minerals in aqueous systems up to 90 degrees C is not lower than it is in homogeneous solution.


Clinical effect of catgut implantation at acupoints for the treatment of simple obesity: A multicentre randomized controlled trial.
Catgut implantation at acupoints (CIA) is a subtype of acupuncture that has been widely used to treat simple obesity, but evidence for its effectiveness remains scarce. The aim of this study is to evaluate the efficacy and safety of treating simple obesity with CIA. This clinical trial aims to evaluate the effectiveness and safety of CIA used for treatment of simple obesity. This is a multicentre, randomized, parallel, sham-controlled clinical trial. A total of 216 patients with simple obesity will be recruited. They will be randomly assigned in a 1:1 ratio to either the CIA group or the sham control group. All treatments will be given once every 2 weeks. The primary outcome measure is the rate of waistline reduction. Secondary outcome measures are the rates of reduction of body measurements, including weight, body mass index (BMI), hipline, waist-hip-ratio (WHR) and body fat percentage (BFP), the changes in scores on scales, including the Impact of Weight on Quality of Life Questionnaire (IWQOL-Lite), Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HAD) and the Self-Esteem Scale (SES), Outcomes will be evaluated at baseline and at weeks 4, 8, 12, 16, 28, and 40, respectively. All adverse events that occur during this study will be recorded. If any participant withdraws from the trial, an intention-to-treat analysis (ITT) will be performed. This is a randomized, sham-controlled trial of CIA treatment for simple obesity. The results of this trial will provide more evidence on whether CIA is efficacious and safe for treating obesity. ClinicalTrials.gov Identifier: NCT02936973. Registered on October 18, 2016.


A label-free oligonucleotide based thioflavin-T fluorescent switch for Ag+ detection with low background emission.
A novel fluorescent Ag(+) sensor was developed based on the label-free silver (I) specific oligonucleotide (SSO) and Thioflavine T (ThT) monomer-excimer switch. C-rich SSO which contain C-C mismatched base pairs can selectively bind to Ag(+) ions and the formed duplexes which constructed by C-Ag(+)-C structure are thermally stabilized without largely altering the double helical structure. ThT give very weak fluorescent in bulk solution and/or in the presence of SSO. However ThT shows high fluorescence in the presence of SSO and Ag(+) at the same time mainly because ThT excimer, which has the high quantum yield, formed and stabilized in the minor or major groove. Based on the discovery, we developed the novel Ag(+) sensor. Under the optimum condition, the selectivity of this system for Ag(+) over other metal ions in aqueous solution is remarkably high, and Ag(+) can be quantified over the dynamic range of 30-450 nM, with a limit of detection of ~16 nM and a linear correlation coefficient of 0.995.


Transvaginal Natural Orifice Transluminal Endoscopic Surgery for Surgical Staging of Early-Stage Ovarian Cancers: A Report of Two Cases.
Surgical staging is essential in the management of ovarian cancers. This staging has traditionally been performed by laparotomy, but minimally invasive techniques are increasingly employed. Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) is a promising technique in the field of gynecological oncology. We report 2 cases of vNOTES surgical staging for suspicious ovarian tumors. We operated on 2 patients aged of 81 and 62 years for low-grade serous ovarian carcinoma and ovarian cystadenofibroma, respectively. We performed surgical staging with a pure vNOTES technique for the first patient and used a hybrid approach for the second. No intraoperative or postoperative complications were observed. We suggest that vNOTES is a feasible and effective approach to surgically manage early-stage ovarian cancers.