Haemodynamic instability secondary to minimally displaced pubic rami fractures: a report of two cases.
We report 2 patients with haemodynamic instability secondary to minimally displaced pubic rami fractures following a fall. Both complained of pain and swelling in the abdomen and groin, and had abdominal distension and bruising in the abdomen, groin, and perineum. All these may be early signs of severe vascular injury and should be treated promptly. Both patients were treated with embolisation of the injured vessels using emergency angiography.


Esters of indole-3-acetic Acid from Avena seeds.
The present studies showed that about 80% of the indole-3-acetic acid extractable from Avena kernels by aqueous acetone was esterified to polymers precipitable by ammonium sulfate and ethanol or acetone. The polymers were positively charged, being adsorbed to cation exchange columns at a pH of 3, or below, and eluted at a pH greater than 4. The polymers were heterogeneous with respect to size, about 5,000 to 20,000 daltons, and charge, exhibiting apparent pK(a) values of 4.2 and 4.7. The polymer fractions contained esterified IAA, anthrone-reactive material that liberated glucose upon acid hydrolysis, phenolic compounds, and peptidic material with a high proportion of hydrophobic amino acids. Since the esterified IAA was unstable, establishing polymer purity was not possible, and the designation IAA-glucoprotein fraction was adopted.Dehusked Avena kernels contained 8 mg/kg total IAA of which 5.5% was free and 94.5% esterified. IAA bound through a peptidic linkage was present, but in only trace amounts.


Effect of substance use on premature mortality among severely hypertensive African Americans.
Low-income African Americans residing in impoverished neighborhoods confront myriad barriers to adhering to antihypertensive regimens. Substance use may thwart medication adherence and lifestyle modification efforts, which has implications for excess cardiovascular disease mortality. The Inner-City Hypertension and Body Organ Damage (ICHABOD) Study was a longitudinal cohort study that evaluated causes of mortality among African Americans who lived in urban areas, had severe, poorly controlled hypertension, and were admitted to a local hospital between 1999-2001 and 2002-2004. The authors employed Cox proportional hazards models to assess mortality associated with illicit substance use, including use of heroin and cocaine, as well as by use of tobacco and alcohol. Among192 participants with poorly controlled hypertension, 30% were active illicit substance users (specifically, 22.7% heroin users, 19.8% were cocaine users, and 30.7% were both cocaine and heroin users). The mean age among substance non-users was 52.3 years versus 48.7 years among those reporting current use. Mortality over 7.6 years of follow-up was 52.5% among substance users and 33.8% among nonusers (p-value, 0.01). After adjusting for potential confounders, the hazard ratio (HR) for cocaine use was 2.52 (95% confidence interval (CI) 1.38-4.59), while the HR for heroin use was 2.47 (95% CI 1.42-4.28) and the HR for both was 2.75 (95% CI 1.60-4.73). Substance use was associated with increased mortality among urban black Americans with poorly controlled hypertension. These data suggest the need for targeted interventions to support African Americans who have poorly controlled hypertension and use illicit substances, as a means of reducing excess mortality.


A phase 1b open-label dose-finding study of ustekinumab in young adults with type 1 diabetes.
We assessed the safety of ustekinumab (a monoclonal antibody used in psoriasis to target the IL-12 and IL-23 pathways) in a small cohort of recent-onset (<100 days of diagnosis) adults with type 1 diabetes (T1D) by conducting a pilot open-label dose-finding and mechanistic study (NCT02117765) at the University of British Columbia. We sequentially enrolled 20 participants into four subcutaneous dosing cohorts: (i) 45 mg loading weeks 0/4/16, (ii) 45 mg maintenance weeks 0/4/16/28/40, (iii) 90 mg loading weeks 0/4/16, and (iv) 90 mg maintenance weeks 0/4/16/28/40. The primary endpoint was safety as assessed by an independent data and safety monitoring board (DSMB) but we also measured mixed meal tolerance test C-peptide, insulin use/kg, and HbA1c. Immunophenotyping was performed to assess immune cell subsets and islet antigen-specific T cell responses. Although several adverse events were reported, only two (bacterial vaginosis and hallucinations) were thought to be possibly related to drug administration by the study investigators. At 1 year, the 90 mg maintenance dosing cohort had the smallest mean decline in C-peptide area under the curve (AUC) (0.1 pmol/ml). Immunophenotyping showed that ustekinumab reduced the percentage of circulating Th17, Th1, and Th17.1 cells and proinsulin-specific T cells that secreted IFN-γ and IL-17A. Ustekinumab was deemed safe to progress to efficacy studies by the DSMB at doses used to treat psoriasis in adults with T1D. A 90 mg maintenance dosing schedule reduced proinsulin-specific IFN-γ and IL-17A-producing T cells. Further studies are warranted to determine if ustekinumab can prevent C-peptide AUC decline and induce a clinical response.


Lower extremity joint loading during level walking with Masai barefoot technology shoes in overweight males.
The purpose of this study was to evaluate the effects of Masai barefoot technology (MBT) shoes on lower extremity joint loading in overweight males during level walking. Therefore, lower extremity kinematics, kinetics, and muscle electromyographic signals of the vastus lateralis (VL), biceps femoris (BF), and gastrocnemius medialis (GM) were recorded in 10 overweight males at a self-chosen walking speed with MBT shoes and conventional shoes. Selected peak joint moments, maximal joint force loading rates, mean muscle intensities, and co-activation indices of the VL/BF, as well as of the VL/GM were analyzed and compared for the two shoe conditions using paired Student's t-tests (α=0.05). Results showed that walking with MBT shoes reduced first peak knee adduction moments in overweight subjects. During midstance and terminal stance, increases in VL/GM co-activation, accompanied by increases in VL and GM (only terminal stance) intensities were found for the MBT situation. Kinetic variables analyzed to assess ankle and hip joint loading did not exhibit any statistical differences. These results suggest that using MBT shoes diminishes medial compartment loads at the knee without overloading hip or ankle joints in overweight males. However, the additional muscle loading should not be overlooked, and warrants further investigation.


Development and Validation of a Model for Predicting the Risk of Death in Patients with Acinetobacter baumannii Infection: A Retrospective Study.
This study aimed to develop and validate a personalized prediction model of death risk in patients with Acinetobacter baumannii (A. baumannii) infection and thus guide clinical research and support clinical decision-making. The development group is comprised of 350 patients with A. baumannii infection admitted between January 2013 and December 2015 in The First Affiliated Hospital of Anhui Medical University. Further, 272 patients in the validation group were admitted between January 2016 and December 2018. The univariate and multivariate logistic regression analyses were used to determine the independent risk factors for death with A. baumannii infection. The nomogram prediction model was established based on the regression coefficients. The discrimination of the proposed prediction model was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curves and decision curve analysis (DCA). The calibration diagram was used to evaluate the calibration degree of this model. The infectious source, carbapenem-resistant A. baumannii (CRAB), hypoalbuminemia, Charlson comorbidity index (CCI), and mechanical ventilation (MV) were independent risk factors for death. The AUC of the ROC curve of the two groups was 0.768 and 0.792, respectively. The net income was higher when the probability was between 30% and 80%, showing a strong discrimination capacity of the proposed model. The calibration curve swung around the 45° oblique line, indicating a high degree of calibration. The proposed model helped predict the risk of death from A. baumannii infection, improve the early identification of patients with a higher risk of death, and guide clinical treatment.


Enhancement of contrast sensitivity and losses of chromatic discrimination with tinted lenses.
Tinted lenses for everyday use should not impair visual acuity and contrast sensitivity or cause radical changes in color perception. The main aim of this study was to compare the performance in contrast detection and color discrimination tasks of a set of tinted lenses with that of gray filters of equal luminance under D65. The contrast sensitivity functions of 10 observers were measured using sinusoidal gratings of mean luminance of 13 cd/m2 by the adjustment method. Color discrimination thresholds from white (x = 0.313, y = 0.330), green (x = 0.346, y = 0.407), and blue (x = 0.280, y = 0.253) were measured along 12 directions in the CIE-1931 xy diagram with and without lenses. Green, brown, and blue filters did not cause significant changes in contrast sensitivity compared with a gray filter of equal luminance, although chromatic discrimination was disturbed. Yellow and orange filters improved achromatic contrast at certain spatial frequencies, but impaired chromatic discrimination. Compared with gray filters of the same luminance, yellow filters may be useful when enhancement of low achromatic contrasts is desirable, although overall brightness decrements may occur. Nevertheless, these lenses cause tritan-like defects with discrimination losses increasing with the cutoff wavelength.


A Biomaterial-Based Hedging Immune Strategy for Scarless Tendon Healing.
Scarring rather than regeneration, is an inevitable outcome of unbalanced amplifications of inflammation-destructive signals and atresia of the regenerative niche. However, identifying and effectively hedging against the risk of scarring and realizing the conversion of regenerative cues remain difficult. In this work, a hedging immune strategy based microfibrous membrane (Him-MFM), by tethering distearoyl phosphoethanolamine layer-supported copoly(lactic/glycolic acid) electrospun fibers with identified CD11b+ /CD68+ scarring subpopulation membranes in the immune landscape after tendon injury to counterweigh tissue damage, is reported. Him-MFM, carrying relevant risk receptors is shown to shift high type I biased polarization, alleviate apoptosis and metabolic stress, and mitigate inflammatory tenocyte response. Remarkably, the hedging immune strategy reverses the damaged tendon sheath barrier to the innate IL-33 secretory phenotype by 4.36 times and initiates the mucous-IL-33-Th2 axis, directly supplying a transient but obligate regenerative niche for sheath stem cell proliferation. In murine flexor tendon injury, the wrapping of Him-MFM alleviates pathological responses, protects tenocytes in situ, and restores hierarchically arranged collagen fibers covered with basement membrane, and is structurally and functionally comparable to mature tendons, demonstrating that the hedging immunity is a promising strategy to yield regenerative responses not scarring.


Direct Detection of the Substrate Uptake and Release Reactions of the Light-Driven Sodium-Pump Rhodopsin.
For membrane transporters, substrate uptake and release reactions are major events during their transport cycles. Despite the functional importance of these events, it is difficult to identify their relevant structural intermediates because of the requirements of the experimental methods, which are to detect the timing of the formation and decay of intermediates and to detect the timing of substrate uptake and release. We report successfully achieving this for the light-driven Na+ pump rhodopsin (NaR). Here, a Na+-selective membrane, which consists of polyvinyl chloride and a Na+ ionophore, was employed to detect Na+ uptake and release. When one side of the membrane was covered by the lipid-reconstituted NaR, continuous illumination induced an increase in membrane potential, which reflected Na+ uptake by the photolyzed NaR. Via use of nanosecond laser pulses, two kinds of data were obtained during a single transport cycle: one was the flash-induced absorbance change in NaR to detect the formation and decay of structural intermediates, and the other was the flash-induced change in membrane potential, which reflects the transient Na+ uptake and release reactions. Their comparison clearly indicated that Na+ is captured and released during the formation and decay of the O intermediate, the red-shifted intermediate that appears in the latter half of the transport cycle.


A bio-inspired self-recoverable polyampholyte hydrogel with low temperature sensing.
Hydrogel-based flexible sensors have been extensively investigated, but inevitably, some hydrogels will not work properly at low temperature or recover their original property after deformation. In this work, a polyampholyte hydrogel was successfully prepared by introducing zwitterionic monomers with hydrophobic association. The electrostatic interaction based on polyelectrolyte provides excellent stretchability, fatigue resistance and self-recovery. It was important that the hydrogel, as an excellent strain sensor, exhibited a high electrical conductivity of 0.041 S cm-1, a low temperature resistance of -31.7 °C, and a high sensitivity in the strain range of 0-500%. The hydrogel sensor is used for human motion detection, including joint movement, vocalization, and walking. Predictably, the hydrogel will provide stable performance in a complex temperature environment and exhibited a wide range of applications in physiological signal monitoring, electronic skin and soft robots.


[A case of long-term survival after curative resection of advanced rectal cancer treated by pre-operative chemoradiotherapy].
We report a long-term survival case of rectal cancer that was initially thought unresectable treated with chemoradiotherapy (CRT). The patient was a 50s female with advanced rectal cancer and liver metastasis. The primary tumor was expanded locally and made abscess around the rectum. We evaluated the primary lesion as unresectable, and we performed CRT after colostomy. After radiation therapy (total 60 Gy) and chemotherapy with S-1 (3 courses), the primary tumor was remarkably reduced. The liver metastasis showed a progressive growth in size but not in number. She underwent complete resection of rectal tumor and partial resection of metastatic liver tumor. Postoperative course was uneventful, and she is alive without a recurrence for 5 years after the surgery.


Detection of HPV16/18 E6 Oncoproteins in Head and Neck Squamous Cell Carcinoma Using a Protein Immunochromatographic Assay.
The accurate diagnostic assessment of clinically relevant human papillomavirus (HPV) infections in patients with head and neck squamous cell carcinoma represents an urgent unmet medical need. The aim of this study was to determine feasibility, accuracy, and clinical significance of HPV16/18 E6 oncoprotein detection on cytological specimens from oropharyngeal squamous cell carcinoma (OPSCC) and neck lymph node metastasis of SCC from unknown primary tumor (CUP) via a protein immunochromatographic assay. Cross-sectional study. Cytological specimens from primary tumor and neck metastases were collected from 34 patients with OPSCC or CUP and applied to a lateral flow format test that detects HPV16 and HPV18 E6 oncoproteins. E6 oncoprotein positivity or negativity in these specimens was compared to the specimens' "HPV-driven" reference status, defined by presence of HPV-DNA in combination with p16INK4a overexpression and/or HPV E6 seropositivity. Eighteen of 29 OPSCC (62%) and three of five CUP (60%) were HPV-driven according to our reference method. The E6 oncoprotein lateral flow test had a sensitivity of 94% (95% CI: 70%-100%) and a specificity of 100% (95% CI: 66%-100%) on primary tumor, and a sensitivity of 88% (95% CI: 64%-99%) and a specificity of 100% (95% CI: 74%-100%) on neck metastases. Test agreement between the E6 lateral flow test and the clinical reference method, HPV-DNA plus p16INK4a was excellent, both for primary lesion and neck metastases. We found the detection of HPV16/18 E6 oncoproteins to be a feasible, highly reliable, and low-invasive method to assess "HPV-driven" status in OPSCC and CUP. II Laryngoscope, 131:1042-1048, 2021.


[Cardiomyopathy associated with uncontrolled self medication of anabolic steroids].
Though doping has become increasingly ostracized in the context of professional sports, an enormous number of unrecorded cases must be assumed in semi-professional competitive sports as well as in popular sports. This holds especially true for those forms of sports which are done in order to obtain a well-proportioned, athletic, healthy looking body. This case report describes a formerly healthy young man who had to be urgently admitted to an intensive care unit due to severe myocardial pump failure. As anamnestic information was insufficient and inadequate, the taking of anabolic steroids in high doses was proven, as their metabolites could be detected by urine analysis. Until now, myocardial contractile dysfunction has persisted for more than twelve months after the initial admission. Though other diagnoses which might have led to this impaired myocardial contractile performance have been excluded, cardiomyopathy associated with the taking of anabolic steroids must be assumed. Even in non-professional and public sports, a widespread abuse of doping substances exists. Hence, cardiomyopathy associated with the misuse of anabolic steroids has to be considered especially in young, formerly healthy patients.


Human granulocyte colony-stimulating factor: its basic aspects and clinical applications.
Human granulocyte colony-stimulating factor (G-CSF), a 20 KD glycoprotein consisting of 174 amino acids, is one of the physiological regulators mainly produced by endothelial cells, monocytes-macrophages and fibroblasts, under various stimulations such as infections. The molecule specifically and markedly stimulates the production of neutrophils associated with an expansion of the hematopoietic stem cells/progenitor cells and elevates the functional activities of neutrophils. Under favor of the unique biological activities, recombinant human G-CSF (rhG-CSF) has now become an epoch-making agent for the purposes of reduction of bacterial/fungal infections, particularly in neutropenias of various causes, increased dose intensity of chemotherapeutic drugs in cancers, and solving various problems in hematopoietic stem cell transplantation.


Dual-action cephalosporins: cephalosporin 3'-quinolone carbamates.
A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function. Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibacterial spectrum derived from both cephalosporin-like and quinolone-like activities, suggesting a dual mode of action. Studies to elucidate details of the mechanism of action have been inconclusive. Ciprofloxacin liberated as a consequence of bacterial enzyme-mediated reactions may contribute to the second mode of action, although some evidence indicates that the intact carbamate-linked bifunctional molecules may possess intrinsically both beta-lactam and quinolone activities.


[Expression and significance of β-catenin and NF-κB signaling pathway in knee osteoarthritis synovial inflammation].
To explore expression of β-catenin and NF-κB signaling pathway in synovial tissue of rats with different degrees of knee osteoarthritis (KOA). Forty-eight SPF male rats weighed (200±20) g were randomly divided into three groups, namely model group (32 rats), sham operation group (8 rats) and control group (8 rats). KOA model rats were established by Hulth method, and 8 rats were killed at 2, 4, 8, 12 weeks respectively after modeling, in order to establish KOA model rats with moderate, early, mild and severe degree. Sham operation group was only cut off capsule of knee joint and suture to exclude interference factor, control group was untreated. Behavior, synovial hyperplasia and cartilage degeneration of rats among each group were observed. Expression of NF-κB and signaling pathway and β-catenin in synovial tissue of rats were detected by real-time PCR. KOA rat model was successfully established, and synovial hyperplasia was observed in KOA model at mild and early degree, and then gradually decreased; while cartilage degeneration in the early moderate and severe KOA model was significantly expressed, and gradually aggravated with time. The results of PCR showed that expression of β-catenin in 4-week group (8.57±0.46) and 8-week group (4.23±0.09) were higher than those in control group (P<0.05); expression of TLR-2 in 2-week group (12.04±4.02) and 4-week group (8.54±2.13) were higher than those in control group(P<0.05), and TLR-4 in 2-week group(5.04±0.93), 4-week group (3.29±0.58) and 8-week group (1.63±0.12) were higher than those in control group; expression of NF-κB was significantly higher in 2-week group (10.15±2.04), 4-week group (15.97±4.17), 8-week group (7.69±1.48) and 12-week group (6.70±1.58) than that in control group (P<0.05), and expression of IL-1β was significantly higher in 4-week group (2.79±0.25) and 8-week group (2.46±0.32) than that of control group (P<0.05). On the RNA expression level, both of β-catenin and NF-κB signaling pathways are involved in synovial inflammation in KOA model rats, and they play a regulatory role in expression of IL-1β, degeneration of KOA.


[Immunohistochemical study in astrocytoma].
Seventy-four cases of human astrocytoma were studied with ABC method for GFAP and vimentin. Data indicated that all of the specimens in this series contained two different intermediate filament proteins: GFAP and vimentin. There was a negative correlation between the degree of anaplasia and the number of GFAP-positive cells, but no definite relationship was seen between the degree of anaplasia and the number of vimentin-positive cells. The ratio of V/G might be considered useful in expressing the histological differentiation of astrocytoma. Generally, two immunostainings are used in demonstrating GFAP and vimentin: one for intense perikaryo-staining and the other for cell processes. Both staining patterns are closely related to the histological type but not to the histological grade. Besides, there was a negative correlation between the cell density and the number of GFAP-positive cells.


Impact of pelvic biometric measurements, visceral and subcutaneous adipose tissue areas on trifecta outcome and surgical margin status after open radical retropubic prostatectomy.
There is no sufficient evidence to demonstrate whether more challenging pelvic anatomy affects the functional and oncological outcomes of radical retropubic prostatectomy (RP). The aim of this study was to investigate the impact of pelvic biometric measurements, visceral and subcutaneous adipose tissue areas on trifecta outcome (cancer control, continence and potency) and surgical margin status after open RP. A retrospective study was performed on 270 patients who were diagnosed with clinically localized prostate cancer between 2005 and 2011 and underwent computed tomography imaging before RP. Pelvic bony and soft-tissue measurements, and visceral and subcutaneous adipose tissue area calculations were performed. Patients were evaluated for trifecta outcome and surgical margin status on univariate and multivariate analyses. Subgroup analysis was performed for prostate volume, body mass index (BMI) and D'Amico risk classification. Univariate analysis revealed that patients with trifecta were younger, and had lower prostate-specific antigen (PSA) levels, wider symphysis angle, and narrower prostate width and soft-tissue width (p < 0.05). Patients with positive surgical margins were older, and had higher PSA levels, lower prostate volume and narrower prostate width (p < 0.05). Visceral adipose tissue area was lower in patients with trifecta when BMI was below 25 kg/cm² (p < 0.05). In multivariate analysis, PSA level and symphysis angle were statistically significant for trifecta while PSA level was the only statistically significant variable for positive surgical margins (p < 0.05). Interfemoral index was significant in the low-risk group of D'Amico classification for trifecta outcome. Pelvic biometric measurements and adipose tissue area calculations may help in preoperative planning and the management of RP.


Pulmonary arterial hypertension--contemporary management strategy.
Pulmonary arterial hypertension (PAH) is a severe chronic disorder of pulmonary arteries with progressive precapillary pulmonary hypertension, characterized by poor life quality and very poor prognosis. Unless treated, it causes death within 2-3 years from diagnosis. PAH affects mainly younger women. The treatment of PAH should not only be symptomatic, but also directed towards the improvement in patient's survival and quality of life. Many novel drugs putting together so called specific PAH therapy (endothelin receptor antagonists, prostanoids, phosphodiesterase--5 inhibitors) were tested in randomized trials. PAH management requires a highly individualized approach, state of the art knowledge and adequate experience. Patients therefore should be referred to specialized PAH centers providing both complete diagnosis and therapy. In our region a close co-operation between Czech and Slovak PAH centers has also proved to be profitable. Data sources. Literature retrieval was accessed through MEDLINE using the terms pulmonary hypertension, PAH, diagnosis, treatment. Reference citations from publications identified were reviewed (Ref. 47). Full Text (Free, PDF) www.bmj.sk.


A rare case of a giant cell tumour caused by vitamin D deficiency.
Reparative giant cell granulomas are benign masses of multi-etiological nature, which account for 1%-7% of all benign lesions of the jaws. The objective of this case report is to present the relationship between isolated vitamin D deficiency and the development of reparative giant cell granuloma.Herein, we present the case of a 70-year-old female patient with a painless mass of increased mobility in the mandibular region, and pain in the involved teeth. After histological confirmation and laboratory screening, а reparative giant cell granuloma caused by serious deficiency of vitamin D3 - (25-OH)D was diagnosed. The treatment protocol included surgical removal of the lesion and vitamin D replacement therapy.In rare cases, this type of lesion can be a primary manifestation of vitamin D deficiency; therefore, it is extremely important to be aware of this pathology.


The abundance and diversity of arbuscular mycorrhizal fungi are linked to the soil chemistry of screes and to slope in the Alpic paleo-endemic Berardia subacaulis.
Berardia subacaulis Vill. is a monospecific genus that is endemic to the South-western Alps, where it grows on alpine screes, which are extreme habitats characterized by soil disturbance and limiting growth conditions. Root colonization by arbuscular mycorrhizal fungi (AMF) is presumably of great importance in these environments, because of its positive effect on plant nutrition and stress tolerance, as well as on structuring the soil. However, there is currently a lack of information on this topic. In this paper, we tested which soil characteristics and biotic factors could contribute to determining the abundance and community composition of AMF in the roots of B. subacaulis, which had previously been found to be mycorrhizal. For such a reason, the influence of soil properties and environmental factors on AMF abundance and community composition in the roots of B. subacaulis, sampled on three different scree slopes, were analysed through microscopic and molecular analysis. The results have shown that the AMF community of Berardia roots was dominated by Glomeraceae, and included a core of AMF taxa, common to all three scree slopes. The vegetation coverage and dark septate endophytes were not related to the AMF colonization percentage and plant community did not influence the root AMF composition. The abundance of AMF in the roots was related to some chemical (available extractable calcium and potassium) and physical (cation exchange capacity, electrical conductivity and field capacity) properties of the soil, thus suggesting an effect of AMF on improving the soil quality. The non-metric multidimensional scaling (NMDS) ordination of the AMF community composition showed that the diversity of AMF in the various sites was influenced not only by the soil quality, but also by the slope. Therefore, the slope-induced physical disturbance of alpine screes may contribute to the selection of disturbance-tolerant AMF taxa, which in turn may lead to different plant-fungus assemblages.


Gender characterization in a large series of Brazilian patients with spondyloarthritis.
An increasing number of women have been diagnosed with spondyloarthritis (SpA) in recent decades. While a few studies have analyzed gender as a prognostic factor of the disease, no studies have addressed this matter with a large number of patients in South America, which is a peculiar region due to its genetic heterogeneity. The aim of the present study was to analyze the influence of gender on disease patterns in a large cohort of Brazilian patients with SpA. A prospective study was carried out involving 1,505 patients [1,090 males (72.4%) and 415 females (27.6%)] classified as SpA according to the European Spondyloarthropaties Study Group criteria who attended at 29 reference centers for rheumatology in Brazil. Clinical and demographic variables were recorded and the following disease indices were administered: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Radiologic Index (BASRI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), and Ankylosing Spondylitis Quality of Life (ASQoL). Ankylosing spondylitis (AS) was the most frequent disease in the group (65.4%), followed by psoriatic arthritis (18.4%), undifferentiated SpA (6.7%), reactive arthritis (3.3%), arthritis associated to inflammatory bowel disease (3.2%), and juvenile SpA (2.9%). The male-to-female ratio was 2.6:1 for the whole group and 3.6:1 for AS. The females were older (p < 0.001) and reported shorter disease duration (p = 0.002) than the male patients. The female gender was positively associated to peripheral SpA (p < 0.001), upper limb arthritis (p < 0.001), dactylitis (p = 0.011), psoriasis (p < 0.001), nail involvement (p < 0.001), and family history of SpA (p = 0.045) and negatively associated to pure axial involvement (p < 0.001), lumbar inflammatory pain (p = 0.042), radiographic sacroiliitis (p < 0.001), and positive HLA-B27 (p = 0.001). The number of painful (p < 0.001) and swollen (p = 0.006) joints was significantly higher in the female gender, who also achieved higher BASDAI (p < 0.001), BASFI (p = 0.073, trend), MASES (p = 0.019), ASQoL (p = 0.014), and patient's global assessment (p = 0.003) scores, whereas the use of nonsteroidal anti-inflammatory drugs (p < 0.001) and biological agents (p = 0.003) was less frequent in the female gender. Moreover, BASRI values were significantly lower in females (p < 0.001). The female gender comprised one third of SpA patients in this large cohort and exhibited more significant peripheral involvement and less functional disability, despite higher values in disease indices.


Longitudinal assessment of pigtailed macaque lower genital tract microbiota by pyrosequencing reveals dissimilarity to the genital microbiota of healthy humans.
Vaginal bacterial communities play an important role in human health and have been shown to influence HIV infection. Pigtailed macaques (Macaca nemestrina) are used as an animal model of HIV vaginal infection of women. Since the bacterial microbiota could influence retrovirus infection of pigtailed macaques, the genital microbiota in 10 cycling macaques was determined by pyrosequencing. The microbiota of all macaques was polymicrobial with a median of 13 distinct genera. Strikingly, the genera Sneathia and Fusobacterium, both in the phylum Fusobacteria, accounted for 18.9% and 13.3% of sequences while the next most frequent were Prevotella (5.6%), Porphyromonas (4.1%), Atopobium (3.6%), and Parvimonas (2.6%). Sequences corresponding to Lactobacillus comprised only 2.2% of sequences on average and were essentially all L. amylovorus. Longitudinal sampling of the 10 macaques over an 8-week period, which spanned at least one full ovulatory cycle, showed a generally stable presence of the major types of bacteria with some exceptions. These studies show that the microbiota of the pigtailed macaques is substantially dissimilar to that found in most healthy humans, where the genital microbiota is usually dominated by Lactobacillus sp. The polymicrobial makeup of the macaque bacterial populations, the paucity of lactobacilli, and the specific types of bacteria present suggest that the pigtailed macaque microbiota could influence vaginal retrovirus infection.


Improving the performance of edible food packaging films by using nanocellulose as an additive.
Due to the environmental pollution problems caused by plastic-based packaging, the development of edible food packaging films is imminent. However, the performance of most edible packaging films is insufficient to meet practical applications, so recent studies have focused on the research of various fillers to improve film properties. This article reviews recent applications of cellulose nanocrystals (CNC) and cellulose nanofiber (CNF) in edible food packaging films including the effect on thickness, optical properties, barrier properties, water sensitivity, mechanical properties, antioxidant and antimicrobial properties. The main conclusion of this review is that the incorporation of CNC and CNF could significantly improve the performance of edible food packaging films. Particular finding is that although CNC and CNF can be used as excellent addition to improve the performance of edible food packaging films, there is a key "optimum" concentration. In addition, we also found that CNC and CNF as excellent controlled release agents and stabilizers significantly increased the antioxidant and antibacterial properties of edible food packaging films.


Misleading advertising for antidepressants in Sweden: a failure of pharmaceutical industry self-regulation.
The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation. We analyzed all antidepressant advertisements in the Swedish Medical Journal, 1994-2003. The regulation of these advertisements was analyzed using case reports from self-regulatory bodies. The authors independently reviewed this material to investigate: (1) extent of violative advertising; (2) pattern of code breaches; (3) rate at which the system reacted to violative advertising; (4) prevalence of and oversight over claims regarding antidepressant efficacy and disease causality, and (5) costs for manufactures associated with violative advertising. Self-regulatory bodies identified numerous code breaches. Nonetheless, they failed to protect doctors from unreliable information on antidepressants, since as many as 247 of 722 (34%) advertisements breached the industry code. Self-regulatory bodies repeatedly failed to challenge inflated claims of antidepressant efficacy, lending evidence of lax oversight. On average, 15 weeks elapsed between printing and censure of a wrongful claim, and in 25% of cases 47 weeks or more elapsed. Industry paid roughly €108000 in fines for violative advertising, adding an estimated additional average cost of 11% to each purchased violative advertisement, or amounting to as little as 0.009% of total antidepressant sales of around €1.2 billion. Lax oversight, combined with lags in the system and low fines for violations, may explain the Swedish system's failure to pressure companies into providing reliable antidepressants information. If these shortcomings prove to be consistent across self-regulatory settings, and if appropriate measures are not taken to amend shortcomings, many countries may want to reconsider the current balance between self-regulation, and legislative control with government oversight.


Store-operated Ca2+ entry: a key component of the insulin secretion machinery.
Normal plasma glucose level is ensured by the action of insulin, the major hypoglycemic hormone. Therefore, it is not surprising that insulin release from pancreatic β-cells of the islets of Langerhans is controlled by an array of balanced mechanisms in which glucose plays the leading role. Glucose triggers insulin secretion through the well-described pathway of ATP-driven closure of ATP-sensitive potassium channels (KATP), depolarization of the plasma membrane, and opening of the voltage-dependent Ca2+ channels (VDCC). The subsequent rapid rise in cytoplasmic free Ca2+ concentration triggers insulin exocytosis. However, despite more than 40 years of investigation, certain aspects of the intracellular Ca2+ responses to glucose and secretagogues remain unexplained, suggesting the involvement of additional Ca2+ channels. Here, we discuss the emerging role of store-operated Ca2+ channels carried by Orai1 and transient receptor potential canonical 1 (TRPC1) proteins and regulated by the stromal interaction molecule 1 (STIM1) in the control of glucose-induced insulin secretion. The role of other voltage-independent cation channels formed by other members of the TRP channels family is also addressed.


Higher Mixed lineage Kinase Domain-like protein (MLKL) is associated with worst overall survival in adult-type diffuse glioma patients.
Recently, the search for novel molecular markers in adult-type diffuse gliomas has grown substantially, yet with few novel breakthroughs. As the presence of a necrotic center is a differential diagnosis for more aggressive entities, we hypothesized that genes involved in necroptosis may play a role in tumor progression. Given that MLKL is the executioner of the necroptotic pathway, we evaluated whether this gene would help to predict prognosis of adult gliomas patients. We analyzed a publicly available retrospective cohort (n = 530) with Kaplan Meier survival analysis (p<0.0001) and both uni- and multivariate Cox regression models. We determined that MLKL is an independent predictive prognostic marker for overall survival in these patients (HR: 2.56, p<0.001), even when controlled by the CNS5 gold-standard markers, namely IDH mutation and 1p/19q Codeletion (HR: 1.68, p = 0.013). These findings were confirmed in a validation cohort (n = 325), using the same cutoff value. Interestingly, higher expression of MLKL is associated with worse clinical outcome for adult-type diffuse glioma patients, which is opposite to what was found in other cell cancer types, suggesting that necroptosis undertakes an atypical detrimental role in glioma progression.


The RNA helicase DHX16 recognizes specific viral RNA to trigger RIG-I-dependent innate antiviral immunity.
Type I interferons (IFN-I) are essential to establish antiviral innate immunity. Unanchored (or free) polyubiquitin (poly-Ub) has been shown to regulate IFN-I responses. However, few unanchored poly-Ub interactors are known. To identify factors regulated by unanchored poly-Ub in a physiological setting, we developed an approach to isolate unanchored poly-Ub from lung tissue. We identified the RNA helicase DHX16 as a potential pattern recognition receptor (PRR). Silencing of DHX16 in cells and in vivo diminished IFN-I responses against influenza virus. These effects extended to members of other virus families, including Zika and SARS-CoV-2. DHX16-dependent IFN-I production requires RIG-I and unanchored K48-poly-Ub synthesized by the E3-Ub ligase TRIM6. DHX16 recognizes a signal in influenza RNA segments that undergo splicing and requires its RNA helicase motif for direct, high-affinity interactions with specific viral RNAs. Our study establishes DHX16 as a PRR that partners with RIG-I for optimal activation of antiviral immunity requiring unanchored poly-Ub.


Recombinant adeno-associated virus serotype 6 efficiently transduces primary human melanocytes.
The study of melanocyte biology is important to understand their role in health and disease. However, current methods of gene transfer into melanocytes are limited by safety or efficacy. Recombinant adeno-associated virus (rAAV) has been extensively investigated as a gene therapy vector, is safe and is associated with persistent transgene expression without genome integration. There are twelve serotypes and many capsid variants of rAAV. However, a comparative study to determine which rAAV is most efficient at transducing primary human melanocytes has not been conducted. We therefore sought to determine the optimum rAAV variant for use in the in vitro transduction of primary human melanocytes, which could also be informative to future in vivo studies. We have screened eight variants of rAAV for their ability to transduce primary human melanocytes and identified rAAV6 as the optimal serotype, transducing 7-78% of cells. No increase in transduction was seen with rAAV6 tyrosine capsid mutants. The number of cells expressing the transgene peaked at 6-12 days post-infection, and transduced cells were still detectable at day 28. Therefore rAAV6 should be considered as a non-integrating vector for the transduction of primary human melanocytes.


Identification and characterization of protein glycosylation using specific endo- and exoglycosidases.
Enzymatic deglycosylation followed by SDS-PAGE is a valuable method to detect glycan modifications on protein samples. Specific glycosidases were used to remove sugars from glycoproteins in a controlled fashion leaving the protein core intact; the resulting change in molecular weight could be detected as shifts in gel mobility. Alternatively, glycan-sensitive reagents were used to visualize the intensity of glycoprotein bands before and after enzyme treatment. The ease of use of these techniques, which require only basic laboratory instrumentation and reagents, makes them the methodology of choice for initial glycobiology studies. These protocols are also well suited to screen for optimal expression conditions, since multiple glycoprotein samples can be processed at once.


Nitrogenase Cofactor Assembly: An Elemental Inventory.
Nitrogenase is known for its remarkable ability to catalyze the reduction of N2 to NH3, and C1 substrates to short-chain hydrocarbon products, under ambient conditions. The best-studied Mo-nitrogenase utilizes a complex metallocofactor as the site of substrate binding and reduction. Designated the M-cluster, this [MoFe7S9C(R-homocitrate)] cluster can be viewed as [MoFe3S3] and [Fe4S3] subclusters bridged by three μ2-sulfides and one μ6-interstitial carbide, with its Mo end further coordinated by an R-homocitrate moiety. The unique cofactor has attracted considerable attention ever since its discovery; however, the complexity of its structure has hindered mechanistic understanding and chemical synthesis of this cofactor. Motivated by the pressing questions related to the structure and function of the nitrogenase cofactor, one major thrust of our research has been to unravel the key biosynthetic steps of this metallocluster to cultivate a deeper understanding of these reactions and their effects on functionalizing the cofactor. In this Account, we will discuss our recent work that provides insights into how simple Fe and S atoms, along with a single C atom, a heterometallic Mo atom and an organic homocitrate entity, are assembled into one of the most complex metalloclusters known in Nature. Combined biochemical, spectroscopic and structural studies have led us to a working model of M-cluster assembly, which starts with the sequential synthesis of small [Fe2S2] and [Fe4S4] units by NifS/U, followed by the coupling and rearrangement of two [Fe4S4] clusters on NifB concomitant with the insertion of an interstitial carbide and a "9th sulfur" that give rise to a [Fe8S9C] core that is nearly indistinguishable in structure to the M-cluster except for the absence of Mo and homocitrate. This 8Fe core is then matured into an M-cluster on NifEN upon substitution of a Mo-homocitrate conjugate for one terminal Fe atom of the cluster prior to transfer of the M-cluster to its target binding site in the catalytic component of Mo-nitrogenase. Taking stock of the elemental inventory during the cofactor assembly process, the core Fe and S atoms are derived from modular fusion of FeS building blocks, going through 2Fe, 4Fe and 8Fe stages to generate an 8Fe core of the cofactor. However, such a flow of Fe/S along the biosynthetic pathway of the M-cluster is "intervened" by the insertion of C and Mo, which renders the cofactor unique in structure and reactivity. Insertion of C occurs through a novel, radical SAM-dependent mechanism, which involves SN2-type methyl transfer from SAM to a [Fe4S4] cluster pair, hydrogen abstraction of the transferred methyl group by a SAM-derived 5'-dA· radical, and further deprotonation of the resultant methylene radical concomitant with radical chemistry-based coupling and rearrangement of the [Fe4S4] cluster pair into an [Fe8S9C] core. Insertion of Mo, on the other hand, employs an ATPase-dependent mechanism that parallels metal trafficking in the biosynthesis of molybdopterin and CO dehydrogenase cofactors. These findings provide a nice framework for further exploration of the "black box" of nitrogenase cofactor assembly and function.


Endometrial glandular dysplasia: a putative precursor lesion of uterine papillary serous carcinoma. Part II: molecular features.
Endometrial glandular dysplasia (EmGD) may be a newly defined precursor lesion of uterine papillary serous carcinoma (UPSC) by morphology. In this report, we studied molecular changes present in EmGD by the loss of heterozygosity (LOH) approach using laser capture microdissected tissue samples. Nineteen uteri showing at least 1 focus of EmGD by morphology were selected. These cases were 12 UPSC, 2 clear cell carcinomas, 1 mixed uterine papillary serous and endometrioid carcinoma, 1 uterine carcinosarcoma, 1 serous endometrial intraepithelial carcinoma (EIC), and 2 EmGD involving endometrial polyps. Seven microsatellite polymorphic DNA markers (TP53 at 17p, D1S211, and D1S162 at 1p32, D17S1323 at 17q21, D17S1330 at 17q25, D5S346 at 5q, and D2S123 at 2p) were utilized. A total of 123 laser-captured microdissection samples from 19 cases was studied with LOH method. The frequencies and patterns of LOH were analyzed and compared among benign resting endometrium (RE), EmGD, serous EIC, and UPSC. LOH was observed for at least 1 of the 7 markers in all categories of lesions, EmGD, serous EIC, and UPSC. The frequency of LOH for EmGD ranged from 4.2% to 31.3%; the range for serous EIC was 5.9% to 78.6%; and that for UPSC was 7.7% to 62.5%. The most frequent LOH in the 3 above-cited categories of lesions was identified at 17p (TP53) and 1p (D1S162). The frequency of LOH in EmGD with markers of TP53 and D1S162 was significantly higher than in RE (p < 0.05). With markers of D1S211 and D2S123, LOH in EmGD was higher than RE, approaching to a statistically significant level. Compared with foci of serous EIC and UPSC, however, the rate of LOH in EmGD was significantly lower only with TP53 locus (31.3% vs more than 60%, p < 0.05). The difference of LOH frequency with other chromosomal markers between EmGD and serous EIC/UPSC did not reach a statistically significant level. A significantly high concordant LOH pattern was found between foci of EmGD and serous EIC/UPSC (p = 0.05). We conclude that EmGD frequently shows LOH at multiple chromosomal loci, particularly at 17p and 1p. Significantly high concordant LOH frequency between EmGD and paired serous EIC or UPSC strongly suggests that EmGD is a noncancerous precursor lesion of UPSC, probably also of serous EIC. The clinical significance of EmGD needs further studies.


The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways.
Human cartilage glycoprotein 39 (HC-gp39) is a glycoprotein secreted by articular chondrocytes, synoviocytes and macrophages. Increased levels of HC-gp39 have been demonstrated in synovial fluids of patients with rheumatoid or osteoarthritis. The increased secretion of HC-gp39 under physiological and pathological conditions with elevated connective-tissue turnover suggests its involvement in the homoeostasis of these tissues. We report here that HC-gp39 promotes the growth of human synovial cells as well as skin and fetal lung fibroblasts. A dose-dependent growth stimulation was observed when each of the fibroblastic cell lines was exposed to HC-gp39 in a concentration range from 0.1 to 2 nM, which is similar to the effective dose of the well-characterized mitogen, insulin-like growth factor-1. At suboptimal concentrations, the two growth factors work in a synergistic fashion. The use of selective inhibitors of the mitogen-activated protein kinase and the protein kinase B (AKT) signalling pathways indicates that both are involved in mediating the mitogenic response to HC-gp39. Phosphorylation of both extracellular signal-regulated kinases 1/2 and AKT occurred in a dose- and time-dependent fashion upon addition of HC-gp39. Activation of these signalling pathways could also be demonstrated in human chondrocytes. Thus HC-gp39 initiates a signalling cascade in connective-tissue cells which leads to increased cell proliferation, suggesting that this protein could play a major role in the pathological conditions leading to tissue fibrosis.


Inhibitor properties of some 5-substituted uracil acyclonucleosides, and 2,2'-anhydrouridines versus uridine phosphorylase from E. coli and mammalian sources.
Two series of 5-substituted uracil N(1)-acyclonucleosides, each with a different acyclic chain, were examined as inhibitors of uridine phosphorylase from rat intestinal mucosa, and several against the enzyme from Ehrlich ascites cells. In addition, several 5-substituted analogues of 2,2'-anhydrouridine were tested for their inhibitory effects vs a highly purified uridine phosphorylase from Escherichia coli. The results are compared with previously published data for inhibition of the E. coli enzyme by the acyclonucleosides, and of the rat enzyme by the anhydrouridines. In all instances, the inhibitors were active only vs the uridine, but not thymidine, phosphorylase from E. coli, and inhibition was competitive with respect to uridine as substrate. In general, with one or two exceptions, inhibitory effects were more pronounced against the enzyme from mammalian sources. Amongst the acyclonucleoside analogues, the most effective inhibitor of the enzyme from the rat and Ehrlich ascites cells exhibited a Ki = 0.1 microM, comparable to that reported with the Sarcoma-180 enzyme, whereas the Ki for inhibition of the E. coli enzyme was 0.7 microM. By contrast, another effective inhibitor of the bacterial enzyme was 7-fold less potent against the mammalian enzyme. The 2,2'-anhydrouridines were 10- to 30-fold more effective against the rat, as compared to the E. coli, enzyme. The overall quantitative data provide a reasonably good basis for the further design of potent inhibitors for possible use in chemotherapy.


A technique for automatically extracting useful field of view and central field of view images.
It is essential to ensure the uniform response of the single photon emission computed tomography gamma camera system before using it for the clinical studies by exposing it to uniform flood source. Vendor specific acquisition and processing protocol provide for studying flood source images along with the quantitative uniformity parameters such as integral and differential uniformity. However, a significant difficulty is that the time required to acquire a flood source image varies from 10 to 35 min depending both on the activity of Cobalt-57 flood source and the pre specified counts in the vendors protocol (usually 4000K-10,000K counts). In case the acquired total counts are less than the total prespecified counts, and then the vendor's uniformity processing protocol does not precede with the computation of the quantitative uniformity parameters. In this study, we have developed and verified a technique for reading the flood source image, remove unwanted information, and automatically extract and save the useful field of view and central field of view images for the calculation of the uniformity parameters. This was implemented using MATLAB R2013b running on Ubuntu Operating system and was verified by subjecting it to the simulated and real flood sources images. The accuracy of the technique was found to be encouraging, especially in view of practical difficulties with vendor-specific protocols. It may be used as a preprocessing step while calculating uniformity parameters of the gamma camera in lesser time with fewer constraints.


Correspondences among parent, teacher, and student perceptions of adolescents' learning disabilities.
A group of 26 adolescents with learning disabilities (Grades 9 through 12), their parents, and their special education teachers were asked to rate the students' skills in each of 21 specific areas covering general ability, oral language, reading, written language, math, study skills, motivation, social skills, attention, and nonverbal skills. Correspondences in the absolute and relative ratings of parents, teachers, and students across the 21 skill areas were examined. The parents' ratings were consistent with those of the teachers in 16 areas and significantly lower than the teachers in 5 areas. The students' ratings were generally higher than those of their parents and teachers. The student-teacher differences were significant in 6 areas, whereas the student-parent differences were significant in 11 areas. Although generally lower in absolute terms than the ratings of their children, the parents' relative ratings were strikingly parallel to their children's ratings across skill areas (r = 80). Differences in the reference groups used for the ratings did not seem to account for the discrepant ratings. Possible implications of the differing perceptions of students' learning disabilities for students' self-esteem and academic progress are discussed.


Parathyroid hormone gene polymorphism and secondary hyperparathyroidism in hemodialysis patients.
It is well known that genetic factors are involved in the progression of secondary hyperparathyroidism (HPT) in hemodialysis (HD) patients. The purpose of the present study is to determine the relationship between restriction fragment length polymorphisms (RFLPs) of the parathyroid hormone (PTH) gene and serum intact PTH levels in HD patients. Eighty-six HD patients not treated with vitamin D and 80 healthy controls were analyzed. PTH genotypes were determined by polymerase chain reaction and RFLPs of BstBI and DraII. The presence or absence of BstBI and DraII restriction sites of the PTH gene were indicated by B or b and D or d, respectively. There were no significant differences in frequencies of each genotype between HD patients and healthy controls. In HD patients, serum intact PTH levels in the Dd/dd genotype were significantly greater than those in the DD genotype (P < 0.02). However, there was no significant difference in serum intact PTH levels between Bb/bb and BB genotypes. Serum intact PTH levels in the non-BBDD haplotype were significantly greater than those in the BBDD haplotype (P < 0.01). Serum intact PTH levels correlated negatively with serum calcium (Ca) and magnesium (Mg) levels and positively with alkaline phosphatase levels in simple regression analysis. However, in forward stepwise multiple regression analysis, only serum Ca and Mg levels predicted serum intact PTH levels. We conclude that PTH genotypes may influence secondary HPT in HD patients.


Breast Reduction: Surgical Techniques with an Emphasis on Evidence-Based Practice and Outcomes.
After studying this article, the participant should be able to: 1. Understand the relevant anatomy involved in breast reduction. 2. Understand the different breast reduction techniques and their indications. 3. Appreciate the outcomes of these techniques as they pertain to clinical outcomes. This continuing medical education article is designed to refresh one's knowledge on breast reduction while placing emphasis on clinical outcomes. It reviews the relevant anatomy, techniques, and published literature on outcomes, including those that are patient-reported. Photographic representations of most techniques are shown, in addition to supplemental digital video content, to demonstrate each technique. This is designed to be an overview, and the reader should appreciate that no one technique is "right," and the technique used should be selected with patient factors and desired outcomes in mind.


Two-Electron Integrals over Gaussian Geminals.
The evaluation of contracted two-electron integrals over a Gaussian geminal operator is pivotal to diverse quantum chemistry methods. In this article, using the unique factorization properties and the sparsity of these integrals, a novel, near-optimal computation algorithm is presented. Our method employs a combination of recently developed upper bounds, recurrence relations in the spirit of the Head-Gordon-Pople approach, and late- and early-contraction paths in the PRISM style. A detailed study of the FLOP (floating-point operations) cost reveals that the new algorithm is computationally much cheaper than any other previous scheme.


Determining the optical properties of turbid mediaby using the adding-doubling method.
A method is described for finding the optical properties (scattering, absorption, and scattering anisotropy) of a slab of turbid material by using total reflection, unscattered transmission, and total transmission measurements. This method is applicable to homogeneous turbid slabs with any optical thickness,albedo, or phase function. The slab may have a different index of refraction from its surroundings and may or may not be bounded by glass. The optical properties are obtained by iterating an adding-doubling solution of the radiative transport equation until the calculated values of the reflection and transmission match the measured ones. Exhaustive numerical tests show that the intrinsic error in the method is < 3% when four quadrature points are used.


Stress-behavior interactions in hamster tumor growth.
The aim of this study was to investigate the effects of a mechanical stressor and individual behavior differences (separately and in combination) on tumor development in the female Syrian hamster. Studies by other investigators have documented the tumor-enhancing effects of such mechanical stressors as rotational stress. Previous studies by our group found that both size of tumor and time to tumor detection were significantly related to a dimension we call "activation." Eighty 100-day old female Syrian hamsters were placed in circular plexiglas environments in groups of 10. Nineteen days after introduction to the cages, a stress condition was imposed on half the animals (four cages). This consisted of shaking each cage of animals three times a week for three 10-minute intervals. Each group's behavior was videotaped in multiple samples to document pre- and poststress behaviors. Twelve days after the stress condition was initiated, each animal was injected subcutaneously midback with one melanoma tumor fraction. Animals were palpated every three days to determine time to detection of tumor. The videotaped behavior samples were coded for behaviors associated with "activation," inactivity, and interaction. Factor analysis resulted in basically the same first factor of activation found in our previous studies. Hamsters in the nonstressed groups had a significantly longer time to tumor development than those in the stressed groups (22.5 days vs. 12.6 days, p less than 0.005). While no prestress behaviors were associated significantly with time to tumor detection, the poststress activation factor was significantly correlated with longer time to tumor development in the stressed group (r = .61, p less than 0.0001). These results suggest that while the stress condition is more powerful than prestress individual behaviors in affecting the outcome variable, stress appears to interact with the individual behaviors related to "activation" to mitigate the negative effects of stress on tumor growth.


Detection of bone marrow-disseminated breast cancer cells using an RT-PCR assay of MUC5B mRNA.
The evaluation of disseminated epithelial tumor cells in breast cancer patients has generated considerable interest due to its potential association with disease recurrence. Our work was performed to analyze the usefulness of 5 mucin genes expression (MUC2, MUC3, MUC5B, MUC6 and MUC7), using RT-PCR assays, to detect disseminated cancer cells in patients with operable breast cancer. The highest frequencies of positive RT-PCR tests in breast tumor extracts were observed for MUC5B (7/15) and MUC7 (5/12). The best specificity, negative results on all peripheral blood mononuclear (PBMN) cell samples from healthy donors, were shown for MUC2, MUC5B and MUC6 RT-PCR assays. Thus, we selected MUC5B as a target gene for further evaluation. Using a nested RT-PCR, MUC5B mRNA transcripts were detected in 16/31 primary breast tumors (but not in 36 samples of normal PBMN cells) and in the human MCF-7 breast cancer cell line but not in BT20, MDA, T47D and ZR-75 breast cancer cell lines, indicating that MUC5B mRNA is expressed in a population of breast cancer cells. Using this method, 9/46 patients (19.5%) who underwent curative surgery showed positive MUC5B mRNA in bone marrow aspirates obtained prior to surgery, including 5/24 patients (20.8%) with stage I or II breast cancer, without histopathologic lymph node involvement. These results indicate that MUC5B mRNA could be a specific marker applicable to the molecular diagnosis of breast cancer cell dissemination. A comparative evaluation between MUC5B mRNA, cytokeratin 19 (CK19) mRNA and carcinoembryonic antigen (CEA) mRNA in all bone marrow aspirates suggests a putative complementation for molecular detection of disseminated carcinoma cells. Considering that breast cancer is characterized by a great phenotypic heterogeneity, the use of multimarker approach could contribute to tumor cell detection in bone marrow and blood.


Spleen-specific development of germinal centers in rats treated with antithyroid drugs.
The antithyroid drugs (ATDs) methimazole (MMI) and propylthiouracil (PTU) have been used for treatment of hyperthyroidism for more than several decades, despite the fact that they are associated with adverse drug reactions that are thought to be autoimmune mediated. We therefore examined histopathologic responses in the immune system in male and female rats given MMI (2, 20 and 200 mg/kg/day, p.o., in experiment 1; 200 mg/kg/day, p.o., in experiment 3) or PTU (25 and 250 mg/kg/day, p.o., in experiment 2; 200 mg/kg/day, p.o., in experiment 3) for two weeks. In experiments 1 and 2, highest doses of MMI and PTU induced histopathologic changes in the spleen consistent with those in experiment 3 without any changes in the other peripheral lymphoid organs and tissues. In experiment 3, histopathological evaluation of the spleen along with hematological and bone marrow examinations were performed. In both male and female rats, MMI or PTU induced histopathological changes in the spleen characterized by development of germinal centers and an increase in the number of IgG-positive plasma cells in the red pulp; these changes were most prevalent in the MMI-treated female rats. Total red and white blood cell counts were decreased in the MMI-treated male and female rats; lymphocytes and monocytes were lower in male and female rats, respectively. Bone marrow nucleated cells were significantly lower in the MMI-treated males. This is the first study to demonstrate that ATDs induce spleen specific B-cell reactions in rats.


Course of Metal Ions after a Revision of Malfunctioning Metal-on-Metal Total Hip Prostheses.
The present research evaluated the course of cobalt and chromium in the blood and urine after the revision of metal-on-metal with a ceramic-on-polyethylene total hip arthroplasty. Seven patients were enrolled for hip prosthesis revision owing to ascertained damage of the implant. Metals in the blood and urine were evaluated before and after the hip revision. The double measurement before the total hip revision revealed high levels of metal ions (on average, 88.1 µg/L of cobalt in the blood, 399.0 µg/g of creatinine cobalt in the urine, 46.8 µg/L of chromium in the blood, and 129.6 µg/g of creatinine chromium in the urine at the first measurements), with an increasing trend between the first and second dosage. Within a week after the hip revision, the levels of metal ions significantly decreased by approximately half. Four to six months after the operation, the cobalt levels were found near to the reference values, whereas the chromium levels reached 25% of the values measured before the revision. The revision of malfunctioning metal-on-metal implants produced a dramatic decrease of metal ions in biological fluids, although it did not completely rescue the chromium level.


Revisiting the optical properties of Nd doped yttrium orthovanadate.
Neodymium doped YVO(4) is becoming an increasingly popular material for solid state lasers. Among the advantages of vanadates over more traditional materials are that the absorption cross section at 808 nm is significantly larger, the emission cross sections are higher, leading to lower lasing thresholds, and the bandwidth for pump absorption is higher. We report new measurements of the refractive index and thermo-optic coefficient of this material that will aid in the design of laser cavities and other nonlinear optical elements.


Highly Luminescent and Stable Organic-Inorganic Hybrid Films for Transparent Luminescent Solar Concentrators.
Here, a highly luminescent, stable, and visible-transparent organic-inorganic hybrid film was in situ synthesized in a siloxane-polyether (di-ureasil) sol-gel process by dissolving a 4-hydroxy-2-methyl-1,5-naphthyridine-3-carbonitrile (2mCND) ligand and a europium(III) ion. Doping a europium(III) complex into di-ureasil achieves an boost in photoluminescence quantum efficiency (PLQY) from 23.25 to 68.9%. In particular, the excellent photostability of the hybrid film was demonstrated after a 15 h aging experiment in strong UV-LED irradiation (∼468 mW/cm2). Compared to the polymethyl methacrylate (PMMA) matrix, di-ureasil containing a europium(III) complex shows an improved UV resistance, making it a promising candidate for various photonic applications. By integrating the hybrid film onto an acrylic substrate, a transparent luminescent solar concentrator (LSC) was fabricated, which reveals an optical conversion efficiency of ∼0.51% with a G factor of 3.1 at an optical transmission level of ∼90%. Such an LSC could be of particular interest in future transparent photovoltaic windows.


Effect of a specific supplement enriched with n-3 polyunsaturated fatty acids on markers of inflammation, oxidative stress and metabolic status of ear, nose and throat cancer patients.
Malnutrition affects 40-50% of patients with ear, nose and throat (ENT) cancer. The aim of this study was to assess changes induced by a specific nutritional supplement enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes, as compared with a standard nutritional supplement, on markers of inflammation, oxidative stress and metabolic status of ENT cancer patients undergoing radiotherapy (RT). Fourteen days after starting RT, 26 patients were randomly allocated to one of two groups, 13 supplemented with Prosure, an oncologic formula enriched with n-3 polyunsaturated fatty acids, fiber and greater amounts of proteins and electrolytes (specific supplement), and 13 supplemented with Standard-Isosource (standard supplement). Patients were evaluated before RT, and 14, 28 and 90 days after starting RT. The results showed that there were no significant differences between the groups, but greater changes were observed in the standard supplement group, such as a decline in body mass index (BMI), reductions in hematocrit, erythrocyte, eosinophil and albumin levels, and a rise in creatinine and urea levels. We concluded that metabolic, inflammatory and oxidative stress parameters were altered during RT, and began to normalize at the end of the study. Patients supplemented with Prosure showed an earlier normalization of these parameters, with more favorable changes in oxidative stress markers and a more balanced evolution, although the difference was not significant.


DNA double strand cleavage via interstrand hydrogen atom abstraction.
Double strand breaks (DSBs) are the most deleterious form of DNA damage. Natural products that produce them are potent cytotoxic agents. Designing molecules that produce DSBs via a single chemical event is challenging. We determined that formation of a C4'-nucleotide radical in duplex DNA under aerobic conditions gives rise to a DSB. The original radical yields a strand break containing a peroxyl radical, which initiates opposite strand cleavage via C4'-hydrogen atom abstraction. This mechanism provides the impetus to design DNA damaging agents that produce DSBs by abstracting a single hydrogen atom from the biopolymer.


Argatroban therapy in heparin-induced thrombocytopenia with hepatic dysfunction.
We evaluated the dosing requirements in argatroban-treated patients with heparin-induced thrombocytopenia (HIT) and hepatic dysfunction, and compared efficacy and safety outcomes with historical control patients. Retrospective analysis. Inpatient setting. Patients with hepatic dysfunction, defined as total bilirubin > 25.5 micromol/L (1.5 mg/dL), aspartate aminotransferase >100 IU/L, and/or alanine aminotransferase >100 IU/L, were identified from previous multicenter, historical-controlled studies of argatroban therapy in HIT. Argatroban, adjusted to maintain activated partial thromboplastin times (aPTTs) 1.5 to 3 times baseline in the experimental group, vs no direct thrombin inhibition in the historical control patients. The analysis population included 82 argatroban patients and 34 historical control patients with hepatic impairment, of whom approximately 50% in each group had renal dysfunction (defined as a serum creatinine level > 1.3 mg/dL). The argatroban dosage was 1.6 +/- 1.1 microg/kg/min (mean +/- SD) over a mean 5-day course of therapy. Significantly lower doses were used in patients with elevated vs normal total bilirubin levels (0.8 +/- 0.6 microg/kg/min vs 1.7 +/- 0.8 microg/kg/min, p = 0.0063) and in patients with hepatic/renal dysfunction vs hepatic dysfunction alone (1.2 +/- 1.1 microg/kg/min vs 2.0 +/- 1.1 microg/kg/min, p < 0.001). The aPTT 24 h after argatroban initiation was 69 +/- 22 s, with 80% of patients having a therapeutic level of anticoagulation. Thirty-four argatroban-treated patients (41.5%) and 17 control patients (50.0%) experienced the 37-day composite end point of death, amputation, or new thrombosis (p = 0.32). Argatroban significantly reduced new thrombosis (8.5% vs 26.5%, p = 0.012). Major bleeding was similar between treatment groups (4.9% vs 2.9%, p = 0.684). Hepatic dysfunction affects argatroban dosing, with reduced doses required particularly in patients with serum total bilirubin levels > 25.5 micromol/L (1.5 mg/dL) or combined hepatic/renal dysfunction. Individual mean aPTT-adjusted doses typically remain > or = 0.5 microg/kg/min, supporting the recommendation of 0.5 microg/kg/min as a conservative initial dose for most patients with hepatic impairment. Argatroban, with proper initial dosing and monitoring, can provide safe and effective antithrombotic therapy in patients with HIT and hepatic impairment.


Caregiver rating bias in mild cognitive impairment and mild Alzheimer's disease: impact of caregiver burden and depression on dyadic rating discrepancy across domains.
Caregivers of individuals with dementia are biased in their rating of mental health measures of the care receiver. This study examines caregiver burden and depression as predictors of this bias for mild cognitive impairment and mild Alzheimer's disease in different domains. The sample consisted of 202 persons: 60 with mild cognitive impairment, 41 with mild Alzheimer's disease, and 101 caregivers. Discrepancy scores were calculated by subtracting the mean caregiver score from the respective mean patient score on the following assessment instruments: the Geriatric Depression Scale, Apathy Evaluation Scale, Bayer-Activities of Daily Living Scale, and Quality of Life-AD scale. Caregiver burden and depression were assessed by the Zarit Burden Interview and the Center for Epidemiologic Studies Depression Scale. Intraclass correlation coefficients were low for apathy (0.38), daily functioning (0.38), and quality of life (0.30) and moderate for depression (0.49). These domains showed negative rating discrepancies, which indicates caregiver rating bias for all four domains. Regression analyses revealed that caregiver burden significantly contributed to explaining these discrepancies in the domains apathy, daily functioning, and quality of life. Caregiver rating bias can be attributed to caregiver burden. When caregiver burden is present, data based on caregiver ratings should therefore be interpreted with caution.


Metocurine kinetics in patients undergoing operations requiring cardiopulmonary bypass.
Metocurine kinetics were determined in 10 patients undergoing operations requiring hypothermic cardiopulmonary bypass (CPB) and nine patients of similar age undergoing operations of similar duration but not requiring CPB. The metocurine dosage regimen was a bolus of 0.3 mg/kg given concomitantly with the commencement of an infusion at a rate of 0.04 mg/kg/hr; this regimen was designed to produce and maintain a plasma metocurine concentration associated with 95% depression of the twitch response. Metocurine kinetics were affected minimally by hypothermic CPB. The kinetic parameters including volumes of distribution at steady state of 0.35 L/kg and 0.34 L/kg and elimination clearances of 1.3 ml/min/kg and 1.1 ml/min/kg in the control and CPB groups, respectively, are in agreement with the results of others. Changes in neuromuscular blockade with the onset of CPB and the return to original blockade intensities with rewarming suggest a decreased sensitivity to the effects of metocurine at lower temperatures.


Pyrene-fused subphthalocyanine.
A pyrene-fused subphthalocyanine synthesized from a reaction of 2,7-di-tert-butyl-4,5,9,10-tetracyanopyrene and tetrafluorophthalonitrile exhibits red-shifted Q-band absorption and a unique linear arrangement in the solid state caused by a π-π stacking interaction. The concave conjugation of the SubPc moiety and the planar conjugation of the pyrene moiety enhanced its co-crystallization with C(60) molecules.


Plaque and chronic inflammatory periodontal disease. A question of ecology.
The nature of the relationship between dental plaque and chronic inflammatory periodontal disease (CIPD) remains unclear, although there is no doubt that plaque is the direct cause. Non-specific, specific and exogenous hypotheses have been proposed to explain plaque-host relationships. Current evidence indicates that plaque is part of the natural human microflora, one of many such in nature, and that disruption of oral microbial ecology, due primarily to diet texture changes, leads to gingivitis and periodontitis. These result in increased plaque accumulation, and particularly in increased interdental effective plaque thickness. The latter leads to alterations in plaque ecology, particularly increasing anaerobiosis, with resultant shifts in proportions of its constituent species. These shifts are responsible for the increased counts of, for example, Bacteroides gingivalis, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Wolinella recta, spirochaetes and others, associated with chronic periodontitis in its various forms. Measures to prevent or control chronic periodontitis should aim, not to eliminate plaque, which ignores ecology and would compromise host defence, but to restore the species distribution in plaque to that compatible with health.


Distribution of serotypes and antimicrobial resistance genes among Streptococcus agalactiae isolates from bovine and human hosts.
To better understand the emergence and transmission of antibiotic-resistant Streptococcus agalactiae, we compared phenotypic and genotypic characteristics of 52 human and 83 bovine S. agalactiae isolates. Serotypes found among isolates from human hosts included V (48.1%), III (19.2%), Ia and Ib (13.5% each), and II (5.8%). Among isolates from bovine hosts, molecular serotypes III and II were predominant (53 and 14.5%, respectively). Four and 21 different ribotypes were found among human and bovine isolates, respectively. A combination of ribotyping and serotyping showed that two bovine isolates were indistinguishable from human isolates. Resistance to tetracycline and erythromycin was more common among human (84.6% and 26.9%, respectively) than bovine (14.5% and 3.6%, respectively) isolates. tetM was found in all tetracycline-resistant human isolates, while tetO was the predominant resistance gene among bovine isolates. tet genes were found among various ribotypes. ermB, ermTR, and mefA were detected among erythromycin-resistant human isolates, while ermB was the only erythromycin resistance determinant among isolates from bovine hosts. For isolates from human hosts, erythromycin resistance genes appeared to be associated with specific ribotypes. We conclude that (i) human and bovine S. agalactiae isolates represent distinct populations; (ii) human host-associated S. agalactiae subtypes may occasionally be transmitted to bovines; (iii) while emergence of erythromycin and tetracycline resistance appears to largely occur independently among human and bovine isolates, occasional cross-species transfer of resistant strains or transmission of resistance genes between human- and bovine-associated subtypes may occur; and (iv) dissemination of antibiotic-resistant S. agalactiae appears to include both clonal spread of resistant strains as well as horizontal gene transfer.


Pattern of relapse and outcome of non-metastatic germinoma patients treated with chemotherapy and limited field radiation: the SFOP experience.
Over the last two decades, chemotherapy has been introduced in protocols for patients with intracranial germinoma with the objective of reducing the volume and the dose of irradiation without compromising survival rates. The aim of this work is to critically analyze the pattern of relapse in a cohort of patients with nonmetastatic germinoma prospectively treated with chemotherapy followed by focal field radiation. Data of all germinoma patients registered in the French protocol for intracranial germ cell tumors between 1990 and 1999 were reviewed. The pattern of relapse, management, and outcome were analyzed in 10 of 60 patients who developed a recurrence after initial treatment. In 9 patients, the site of recurrence was local or loco-regional, notably in the periventricular area for 8. One patient only had isolated distant leptomeningeal relapse. The review of the sites of relapse suggests that most recurrences could have been avoided with a larger ventricular field of radiation. Treatment at first relapse included chemotherapy (10 patients), high-dose chemotherapy and stem cell transplant (8 patients), and/or radiation therapy (4 patients). Five patients experienced a second relapse. At a median follow-up of 72 months since the first relapse, 8 patients are alive in second or third remission. This review identified an excess of periventricular relapses when the focal field of radiation is used in the combined management of germinoma. These relapses are predominantly marginal or outside radiation fields. Ventricular field radiation appears a logical alternative to decrease the incidence of such relapses. Future trials should aim at better identifying patients who may benefit from local and ventricular radiation, respectively.


Tropospheric Ozone Perturbations Induced by Urban Land Expansion in China from 1980 to 2017.
Urbanization perturbs air pollutants from a dynamic and thermodynamic perspective, which has inspired extensive investigations in China due to rapid urban land expansion in the past four decades. However, knowledge gaps remain in the long-term and nationwide responses to air pollutants to urbanization. The evolution of tropospheric ozone associated with urban land expansion across China was assessed from 1980 to 2017 using a coupled WRF-Chem model based on a recently updated land use change (LUC) data set. The results revealed that urban-land expansion drove growing ozone trends for this period and contributed about 3-9% to its summer maximum concentrations during the 2010s in major urban agglomerations across China. The association between a long-term change in summer O3 concentrations and LUC after excluding the effect of precursor emissions and meteorological conditions and causes of interannual (short-term) variations in O3 concentrations induced by urban-land expansion were also explored by examining the relationships between ozone fluctuations and meteorological variables.


Motivational reserve: motivation-related occupational abilities and risk of mild cognitive impairment and Alzheimer disease.
Midlife motivational abilities, that is, skills to initiate and persevere in the implementation of goals, have been related to mental and physical health, but their association with risk of mild cognitive impairment (MCI) and Alzheimer's disease (AD) has not yet been directly investigated. This relation was examined with data from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe). A total of 3,327 nondemented participants (50.3% of a randomly selected sample) aged 75-89 years were recruited in primary care and followed up twice (after 1.5 and 3 years). Motivation-related occupational abilities were estimated on the basis of the main occupation (assessed at follow-up II) using the Occupational Information Network (O* NET) database, which provides detailed information on worker characteristics and abilities. Cox proportional hazards models were used to evaluate the relative risk of developing MCI and AD in relation to motivation-related occupational abilities, adjusting for various covariates. Over the 3 years of follow-up, 15.2% participants developed MCI and 3.0% developed AD. In a fully adjusted model, motivation-related occupational abilities were found to be associated with a reduced risk of MCI (HR: 0.77; 95% CI: 0.64-0.92). Motivation-related occupational abilities were associated with reduced risk of AD in ApoE ε4 carriers (HR: 0.48; CI: 0.25-0.91), but not in noncarriers (HR: 0.99; CI: 0.65-1.53). These results suggest that midlife motivational abilities are associated with reduced risk of MCI in general and with reduced risk of AD in ApoE ε4 carriers. Revealing the mechanisms underlying this association may inform novel prevention strategies for decelerating cognitive decline in old age.


PTEN expression is upregulated by a RNA-binding protein RBM38 via enhancing its mRNA stability in breast cancer.
PTEN (phosphatase and tensin homolog gene on chromosome 10), a well-characterized tumor suppressor, is a key regulator of the phosphatidylinositol-3-kinase (PI3K)/AKT pathway involved in cell survival, metastasis and cell renewal. PTEN expression is closely related to the phenotype, prognosis and drug selection in breast cancer. It is mainly regulated by transcriptional and post-transcriptional modifications. RNA binding motif protein 38 (RBM38), an RNA-binding protein (RBP) and a target of P53 family, plays a crucial role in the regulation of cellular processing, especially in post-transcription regulation and gene transcription. In this study, we investigated a new post-transcription regulation mechanism of PTEN expression by RBM38 in breast cancer. Immunohistochemistry, lentivirus transfections, Western blotting analysis, qRT-PCR and ELISA were used to conduct the relation between RBM38 and PTEN. RNA immunoprecipitation, RNA electrophoretic mobility shift and dual-luciferase reporter assays were employed to identify the direct binding sites of RBM38 with PTEN transcript. Colony formation assay was conducted to confirm the function of PTEN in RBM38-induced growth suppression. PTEN expression was positively associated with the expression of RBM38 in breast cancer tissues and breast cancer cells. Moreover, RBM38 stabilized PTEN transcript to enhance PTEN expression via binding to multiple AU/U- rich elements (AREs) in 3'-untranslated region (3'-UTR) of PTEN transcript. Additionally, specific inhibitors of PTEN activity and small interfering (siRNA) of PTEN expression inhibited RBM38-mediated suppression of proliferation, which implied that RBM38 acted as a tumor suppressor partly by enhancing PTEN expression. The present study revealed a new PTEN regulating mechanism that PTEN was positively regulated by RBM38 via stabilizing its transcript stability, which in turn alleviated RBM38-mediated growth suppression.


A personal journey towards any qualified provider in the NHS.
Any Qualified Provider (AQP) is a new and exciting way of organising health care that offers patient choice and cost-effective care. But there are many rumours and 'Chinese whispers' that are causing concern among healthcare workers throughout the UK. Although not all the rumours are false, there is a general misunderstanding of what AQP can provide and its potential to raise standards and lower costs throughout the NHS. This paper asks: can its promises be achieved? It also shows how AQP may work, through a personal experience of commissioning.


Transitional cell carcinoma of the lacrimal sac.
Lacrimal sac tumor is a rare tumor, for which we do not know the exact incidence. Malignant tumors account for 70% of all cases. Epithelial tumors are the most common pathological type and squamous cell carcinoma is the most common of these, a transitional cell carcinoma is rare and has a poor prognosis. The authors report a rare case of transitional cell carcinoma of the lacrimal sac. A 57-year-old woman had tearing on her right eye. The pre-operative diagnosis was possible nasolacrimal duct obstruction with signs of dacryocele. Intraoperatively the authors found a lacrimal mass and a frozen section showed squamous papilloma with dysplasia. The tumor was completely removed and DCR was done. The subsequent pathological report of the right lacrimal sac was papillary transitional cell carcinoma, so medial maxillectomy and resection of the medial inferior orbit with ethmoidectomy were performed. She received radiation and has been tumor-free for 2 years.


Gutta-percha retreatment: effectiveness of nickel-titanium rotary instruments versus stainless steel hand files.
This study compared the cleanliness of the root canal walls after retreatment using nickel titanium (NiTi) rotary and stainless steel (SS) files. Also compared were time of retreatment and canal deviation. Forty extracted canines were step-back prepared and obturated with gutta-percha and sealer. Retreatment was performed either by using chloroform and SS hand files or chloroform and NiTi rotary files. Time for retreatment was recorded. Radiographs of the root canal system before and after retreatment were made. Teeth were split longitudinally, photographed, and projected onto a screen. The amount of gutta-percha/sealer remaining on the canal walls was then traced and measured. The amount remaining was analyzed and compared statistically between NiTi and SS groups by t test. Results showed that the mean percentage of wall coverage by remaining obturating material in the SS group was 13.6% and was 15.2% for the NiTi group. There was no statistically significant difference (p = 0.361). No severe canal deviation occurred with either retreatment method. Mean retreatment time for the SS group was 6.3 min and 7.9 min for the NiTi group; the difference was statistically significant (t test p < 0.001). In conclusion, NiTi rotary and SS hand were similar in material remaining after retreatment, but SS hand was a bit faster.


Multicomponent Theories of Hypnotizability: History and Prospects.
This review addresses multicomponent theories of hypnotizability by focusing on 3 important exemplars from the history of hypnosis research: E. R. Hilgard's (1965) Hypnotic susceptibility; R. E. Shor's (1962) Three dimensions of hypnotic depth; and T.X. Barber's (1999) A comprehensive three-dimensional theory of hypnosis. Taken together, they illustrate the variety of hypnotic phenomena examined in research - overt responses, subjective experiences, and underlying processes - and the ways in which evidence about each has implied the existence of multiple underlying components. Particularly highlighted are the different ways in which the theories conceptualize the joint contribution of multiple individual differences. Also covered is relevant later work by other researchers as well as important issues remaining to be resolved.


Differences in Dietary Patterns among the Polish Elderly: A Challenge for Public Health.
The aim of the study was to assess the diversity of dietary patterns within the elderly, in relation to the region of residence, household structure, and socioeconomic status. The questionnaire was conducted in a group of 427 Polish adults aged 60 and older from June to September 2019. The sample was selected by means of the snowball method in two regions. Principal component analysis (PCA) was used to extract and identify three dietary patterns (factors) from the frequency of eating 32 groups of foods. Logistic regression analysis was used to determine the relationship between the identified dietary patterns (DPs), region, household status, and socioeconomic index (SES). Adherence to the identified DPs, i.e., traditional, prudent, and adverse, was associated with socioeconomic status (SES) and living environment, i.e., living alone, with partner, or with family, while the region did not differentiate them. Less people living with their family were characterized by the frequent consumption of traditional food (the upper tertile of this DP), while more of them often consumed food that was typical for both prudent and adverse DPs (the upper tertiles of these DPs). The presence of a partner when living with family did not differentiate the adherence to DPs. A high SES decreased the chances of adhering to the upper tertiles of the "prudent" and "traditional" DPs, while living with family increased the chances of adhering to both the upper and middle tertiles of the "prudent" DP. Identifying the dietary patterns of the elderly contributes to a better understanding of the food intake of the senior citizens living in different social situations, in order to support public policies and nutritional counseling among this age group.


Evaluation of biological landfill leachate treatment incorporating struvite precipitation and powdered activated carbon addition.
Direct application of aerobic biodegradation for leachate treatment is not feasible due to high concentrations of nitrogen and chemical oxygen demand. Several potential leachate treatment schemes incorporating struvite precipitation as pretreatment and two types of activated sludge processes (conventional activated sludge and batch decant reactor (intermittent cycle extended aeration system [ICEAS process]) with and without addition of powdered activated carbon (PAC) were evaluated in this study. The hydraulic retention times (HRT) of 6 h and 12 h were applied in the biological stages of each process. Treatment schemes incorporating PAC addition showed acceptable results. In the conventional activated sludge process, total chemical oxygen demand (TCOD), soluble chemical oxygen demand (SCOD), NH(3), and P removal rates were 87, 84, 98.3, and 94%, respectively, with HRT of 6 h and 95.8, 95.1, 99.1, and 98.7% with HRT of 12 h. For the ICEAS process, removal rates were 89.3, 87.9, 98.2, and 94% with HRT of 6 h and 95.8, 95, 99.2, and 98.7% with HRT of 12 h. On the basis of these results, it can be concluded that struvite precipitation, followed by activated sludge process with PAC addition, can be a strong alternative leachate treatment, achieving the standards set for effluent discharges to receiving waters.


Solving the fully-connected 15-city TSP using probabilistic DNA computing.
Implementation of DNA computers has lagged behind the theoretical advances due to several technical limitations. These limitations include the amount of DNA required, the efficiency and accuracy of methods to generate and purify answers, and the lack of a reliable method to read the answer. Here we show how to perform calculations using a reasonable amount of DNA with greater efficiency and accuracy and a new readout method that was used to successfully solve a problem with 15 vertices and 210 edges, the largest problem ever solved with DNA. These advances will provide new opportunities for DNA computing to perform practical computations that utilize the massively parallel nature of DNA hybridization.


Pyrroloquinoline quinone: excretion by methylotrophs and growth stimulation for microorganisms.
A marked excretion of pyrroloquinoline quinone (PQQ) by methylotrophs into the culture medium was observed when incubation was prolonged to the late stationary phase. When the organisms were growing vigorously in the early exponential phase, accumulation of PQQ was repressed at a low level. Some evidence was obtained that the excretion of PQQ is related to turnover of quinoproteins of the organisms. The growth stimulation of microorganisms by PQQ was demonstrated using Acetobacter aceti. The presence of PQQ even at the pg/ml level in the culture medium stimulated the bacterial growth by reducing the lag time. The growth stimulating effect of PQQ was observed only by the reduction of the lag time but not by increase in either the subsequent growth rate or the total cell yield. The results indicated that PQQ must have an important role in the initiation of cell reproduction.


The effects of enalapril and sulindac on the dermal response to substance P and neurokinin A.
The effects of pretreatment with enalapril, and sulindac, on the weal response to intradermal injections of substance P and neurokinin A were assessed in a randomised, double-blind, placebo-controlled study. Weal responses to both substance P and neurokinin A depended significantly on dose. Neither enalapril nor sulindac, nor the combination of these agents influenced the responses to either tachykinin. These results do not suggest any role for substance P or neurokinin A in the clinical effects of angiotensin converting enzyme inhibitors.


Substrate distortion contributes to the catalysis of orotidine 5'-monophosphate decarboxylase.
Orotidine 5'-monophosphate decarboxylase (ODCase) accelerates the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP) by 17 orders of magnitude. Eight new crystal structures with ligand analogues combined with computational analyses of the enzyme's short-lived intermediates and the intrinsic electronic energies to distort the substrate and other ligands improve our understanding of the still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion of its methyl substituent bond, 6-amino-UMP shows the competition between the K72 and C6 substituents for a position close to D70, and the methyl and ethyl esters of OMP both induce rotation of the carboxylate group substituent out of the plane of the pyrimidine ring. Molecular dynamics and quantum mechanics/molecular mechanics computations of the enzyme-substrate complex also show the bond between the carboxylate group and the pyrimidine ring to be distorted, with the distortion contributing a 10-15% decrease of the ΔΔG(⧧) value. These results are consistent with ODCase using both substrate distortion and transition-state stabilization, primarily exerted by K72, in its catalysis of the OMP decarboxylation reaction.


5-amino-4-(4-diethylaminophenyl)-2-(4-hydroxyphenyl)-7-(pyrrolidin-1-yl)-1,6-naphthyridine-8-carbonitrile.
In the title compound, C29H30N6O, the naphthyridine moiety is planar with a dihedral angle between the fused rings of 1.9 (1) degrees. The phenol ring is nearly coplanar, while the diethylaminophenyl substituent is orthogonal to the central naphthyridine ring and the pyrrolidine ring makes an angle of 11.2 (1) degrees with it. The O atom of the hydroxy substituent is coplanar with the phenyl ring to which it is attached. The molecular structure is stabilized by a C-H...N-type intramolecular hydrogen bond and the packing is stabilized by intermolecular C-H...pi, O-H...N and N-H...O hydrogen bonds.


[Chronic constrictive pericarditis].
Chronic constrictive pericarditis is a rare condition characterized by an impairment of myocardial relaxation due to limitation by a rigid pericardium. It is most often associated with infection, thoracic radiotherapy and heart surgery. Clinical features are that of chronic heart failure, therefore non-specific and resulting in a delay of several years before diagnosis is made. The echocardiogram and heart catheterization are part of the initial work-up. Surgical treatment consisting in pericardiectomy can be curative if the disease is recognised early. This article makes use of a case report and review of the litterature to discuss the physiopathology, clinical features and management of chronic constrictive pericarditis.