Final diagnosis by fine-needle aspiration biopsy for definitive operation in breast cancer.
This work has been based on 15 years experience with more than 10,000 needle aspiration biopsies of the breast. Fine-needle aspiration biopsy was used in place of open breast biopsy for definitive operation in breast cancer. Our experience with 2,623 aspiration biopsies over a 3 year period has been reviewed. There was a total of 323 cancers, of which 257 (80 percent) were unequivocally diagnosed by fine-needle aspiration biopsy. Definitive operation was performed in 244 of these patients (95 percent) without open biopsy. Thirteen had an excisional biopsy before definitive operation at the request of the referring physician. The sensitivity was 80 percent and the specificity was 98 percent. There were no false-positive diagnoses. The positive predictive value was 100 percent. False-negative diagnoses were made in 9 percent of the patients, half of whom had nonpalpable carcinomas. Our experience shows that fine-needle aspiration biopsy is accurate in the diagnosis of breast cancer, and when the finding is positive, it can be used for definitive breast operation, eliminating the need for open biopsy. A management algorithm has also been presented herein.


Novel mutations in Chinese hypotrichosis simplex patients associated with LSS gene.
Hypotrichosis simplex (HS) is a rare form of hereditary alopecia caused by a variety of genetic mutations. Currently, only four studies regarding LSS-related HS have been reported. In this study, we try to make a definite diagnosis in two unrelated Chinese families with three pediatric patients clinically suspected of HS. Whole-exome sequencing (WES) was performed for these two families to reveal the pathogenic mutation. WES revealed two different compound heterozygous mutations in LSS in two probands that confirmed the diagnosis, including three novel mutations. In this paper, we describe a new accompanying phenotype of teeth dysplasia in a HS patient. Moreover, we provide a review of all reported LSS mutation-related patients and infer some potential genotype-phenotype correlations for the first time.


Multi-agent evolutionary game in the recycling utilization of construction waste.
The recycling utilization of construction waste (CW) is of great importance to reduce waste discharge and protect natural resources. This study investigated the evolutionary decision making process and stable strategies among three stakeholders, including the government agency (GA), waste recycler (WR) and waste producer (WP), involved in CW recycling industry based on the game theory. The main factors that affected the strategies of the stakeholders were analyzed and the tripartite evolutionary game model is provided. The evolutionary stability strategy and stability conditions were analyzed subsequently. A numerical simulation illustrated the effectiveness of the proposed method, with which the evolutionary decision making process and stable strategies among the three stakeholders are simulated. It is shown that the GA plays different roles in different stages of the development of CW recycling industry. In the early stage, the supervision and policies of the GA are critical to improve the proportion of enterprises that implement the recycling strategy. With the mature of the CW recycling industry, it is profitable for enterprises to implement waste recycling, and a high proportion of enterprises choose to implement recycling strategy. Under this circumstance, the GA will gradually decrease their interventions to enterprises, and finally evolve into no supervision. Besides, it also concludes that low penalties and subsidies are not conducive to the evolution of the optimal strategy among the three participants, and excessive supervision costs will reduce the regulatory willingness of the GA, hindering the enthusiasm of WRs and WPs to implement the recycling strategy.


A functional separation of behavioral stereotypy based on naloxone-reversible effects of seryl enkephalinamide: comparison with morphine.
Amphetamine's stereotypic behavioral actions, produced by the stimulant at a moderate dose, were inhibited by the systemic administration of seryl enkephalinamide, D-Ser2-D-Ser5-enkephalinamide, (Wy 42,896). The classical sequelae of stimulatory behavioral events: sniffing, head bobbing, rearing and locomotor activity, were significantly inhibited by the seryl enkephalinamide. Subsequently, pretreatment with the opiate receptor antagonist, naloxone, significantly blocked the inhibitory effects of the seryl enkephalinamide on the stereotypic and locomotor components. Concomitantly, the behavioral stereotypic component, licking, a behavior usually produced by opiates and only high doses of amphetamine, was significantly induced by the seryl enkephalinamide. Pretreatment with naloxone on the stimulatory behavioral effect of licking, produced a significant inhibitory effect. The combination treatment, consisting of both the seryl enkephalinamide and the stimulant amphetamine, caused a naloxone-reversible synergistic effect. These data show that the seryl enkephalinamide, produced concomitant, naloxone-reversible, inhibitory and stimulatory behavioral stereotypic effects. These data are discussed within the context of current neuronal theories which might underly the observed dose-related continuum of behavioral stereotypies produced by morphine and amphetamine.


Screening for ophthalmic disease in older subjects using visual acuity and contrast sensitivity.
Despite early interest in contrast sensitivity as a screening test for ophthalmic disease, most published opinion suggests that there is no benefit over conventional measurement of visual acuity. Taking a primary care perspective of screening, the authors evaluated the ability to discriminate those with any diagnosed ophthalmic disease in a large sample representative of the general population. Retrospective analysis of a clinical, cross-sectional survey. Snellen visual acuity, contrast sensitivity (Arden plates, American Optical contrast sensitivity test), and ophthalmic diagnosis were reported previously. A sample of 3283 subjects, all aged at least 50 years, were selected randomly from residents of a health district in Sydney, Australia. Ophthalmologic diagnosis (ophthalmic disease presence/absence) had been confirmed for 2522 of these subjects. Signal detection techniques (the receiver-operating characteristics function [ROC], quality ROC [QROC], and weighted kappa coefficient of association [kappa(r)]) were used to evaluate test discriminability. Because analyses of right and left eyes were almost identical, only right eye results are presented. Advantages of kappa(r) over ROC were shown. Discrimination of those with diagnosed ophthalmic disease from those without ophthalmic disease was best with Arden plate 7 (kappa0.5 = 0.93) and was better than distance Snellen visual acuity (kappa0.5 = 0.59). Arden plate 7 (6.4 cyc/deg) correctly assigned 96% of subjects at its optimal pass-fail criterion. In the primary care setting, a person older than 50 years of age with reduced contrast sensitivity, as determined by Arden plate 7, requires extra care in subsequent examinations because this person is likely to have an ophthalmic disease.


[Significance of polyamines for the early diagnosis of spontaneous hemoblastoses in AKR mice].
Polyamines levels were studied in various tissue specimens obtained from high-leukemia AKR mice aged 12 months and less. Organ tissues of leukemic animals revealed increased levels of polyamines and changes in their profile. In symptomatic mice, this was matched by relevant morphologic changes. It is inferred that putrescine is a marker of latent leukemia development.


A Single Nucleotide Polymorphism (SNP) in the SLC22A3 Transporter Gene Is Associated With the Severity of Oral Mucositis in Multiple Myeloma Patients Receiving Autologous Stem Cell Transplant Followed by Melphalan Therapy.
It has been reported that expression of OCT3 enhanced the sensitivity to melphalan in cells, indicative of potential roles of OCT3 in melphalan transport. Herein we investigated the association of select single nucleotide polymorphisms in SLC22A3 (gene encoding OCT3) with clinical outcomes in multiple myeloma (MM) patients with hematopoietic autologous stem cell transplants followed by high-dose melphalan therapy. Melphlan concentrations in blood samples from 108 MM patients were measured using liquid chromatography-tandem mass spectrometry (LC-MS/ΜS); genotypes of rs2048327, rs1810126, and rs3088442 in these patients were determined using quatitive RT-PCR assays. Rs3088442 A variant-carriers had a significantly increased risk of severe oral mucositis in comparison with homozygous rs3088442 G-carriers with adjusted odds ratio of 4.00 (95% CI=1.25-14.7; p=0.027). Rs3088442 A carriers tended to have lower creatinine clearance (p=0.10) and higher maximum plasma concentration of melphalan (p=0.07). OCT3 might be involved in melphalan transport in MM patients.


Pharmacological antagonism of Anchietia salutaris extracts on the contraction induced by prostaglandin D2 and U46619 in guinea-pig lung parenchymal strips.
Anchietia salutaris tea is traditionally used in Brazil to treat allergies, suggesting it contains compounds with antagonistic activity on the allergic mediators. We have evaluated extracts and semi-purified fractions of Anchietia salutaris as a source of compounds having this type of antagonism on the contraction induced in guinea-pig lung parenchymal strips and on platelet aggregation and shape change. After 10 min pre-incubation dichloromethane extracts containing 30 or 100 microg mL(-1) inhibited the contraction induced by prostaglandin D2 (PGD2) in guinea-pig lung parenchymal strips with dose ratios (DR) of 0.76+/-0.14 and 0.93+/-0.19, respectively; the amount of inhibition depended both on the concentration and on the time of pre-incubation (DR after 30 min pre-incubation was 1.21+/-0.51). The dichloromethane extract and its semi-purified fractions also inhibited the contractions induced by U46619, a more potent, stable, synthetic agonist of thromboxane A2 (TxA2) prostanoid (TP) receptors, the receptors acted upon by PGD2 to produce lung contractions. The dichloromethane extract did not inhibit the lung parenchymal contractions induced by histamine, leukotriene D4 (LTD4) or platelet-activating factor (PAF). Platelet aggregation induced by U46619, adenosine 5'-diphosphate (ADP) or PAF was not inhibited by the dichloromethane extract. Indeed, the extract potentiated platelet aggregation induced by low concentrations of these agonists and also potentiated the shape change induced by U46619. These results imply that the dichloromethane extract of Anchietia salutaris and its semi-purified fractions contain an active principle that competitively inhibits TxA2 TP receptors, the stimulation of which causes lung parenchymal contraction. The inhibition seems to be selective for this receptor subtype, because the extract fails to inhibit platelet aggregation or shape change. This provides additional support of earlier reports suggesting the occurrence of TP receptor subtypes.


Natural history of facial paraganglioma with 2 decades of follow-up: A case report and literature review.
To report 20 years of natural history data for a facial paraganglioma and provide a comprehensive review of the existing literature. 81-year-old female with a remote history of cardiac arrest while under anesthesia who elected to observe her facial paraganglioma for 20 years. Observation, clinical documentation, radiographic surveillance. Tumor progression, patient symptomatology, and review of management options. The initial presentation of the facial paraganglioma was facial spasm. Over the course of observation, symptoms progressed to include complete facial nerve paralysis, pulsatile tinnitus, and otalgia on the affected side. Radiologic surveillance demonstrated incremental growth and erosion of surrounding structures, including the posterior external auditory canal, stylomastoid foramen, and lateral semicircular canal with near-dehiscence. Twenty-four cases of facial paraganglioma were identified in the extended literature search and are summarized herein. This unique case contributes to the scarce literature surrounding facial paragangliomas by reporting the extended natural history of this disease.


Response properties of neurons in the visual cortex of the rat.
Response properties of neurons in the visual cortex, area 17, of Long Evans pigmented rats were investigated quantitatively with computer-controlled stimuli. Ninety percent of the cells recorded (296/327) were responsive to visual stimulation. The majority (95%, 281/296) responded to moving images and were classified as complex (44%), simple (27%), hypercomplex (13%) and non-oriented (16%) according to criteria previously established for cortical cells in the cat and monkey. The remaining 5% of the neurons responded only to stationary stimuli flashed on-off in their receptive field. Results of this study indicate that neurons of the rat visual cortex have properties similar to those of cells in the striate cortex of more 'visual' mammals.


Stimulation-induced changes at crayfish (Procambarus clarkii) neuromuscular terminals.
The fine structure of neuromuscular terminals of the single excitor axon was examined in the limb stretcher muscle of the crayfish Procambarus clarkii. A morphometric comparison of the neuromuscular terminals of the left and right limbs of a control crayfish showed them to be similiar in qualitative as well as quantitative features. The excitor axon to the stretcher muscle of the right side was stimulated, by backfiring its branches in the adjacent opener muscle, at 20 Hz for 4-5 h per day over 4-5 days. The stretcher muscle on the left side was not stimulated and served as a control. Morphometric analysis of stimulated terminals revealed an increase in the number of dense bars and synaptic vesicles compared to their non-stimulated, contralateral counterparts. Since dense bars are regarded as active sites of transmitter release, changes in their number provide a morphological basis for synaptic plasticity.


FITC-quencher based caspase 3-activatable nanoprobes for effectively sensing caspase 3 in vitro and in cells.
By employing fluorescence resonance energy transfer (FRET) quenching, we rationally designed two new FITC-quencher based nanoprobes for effectively sensing caspase 3 (Casp3) in vitro and in cells. Our nanoprobes hold promise for assessing the chemotherapeutic effect of cancer treatment.


Retainment of membrane binding capacity of non-palmitoylated Gs alpha mutants expressed in COS-1 cells.
Heterotrimeric guanine nucleotide binding regulatory proteins (G proteins) transduce extracellular signals into intracellular signals by coupling receptors and effectors. Because most of the G protein-coupled receptors are integral proteins, the G proteins need to have a membrane binding capacity to receive signals from the receptors. The alpha subunit of G protein binds tightly to the cytoplasmic face of the plasma membrane without any membrane spanning domain. Fatty acylation of G alpha with myristic acid or palmitic acid, in addition to the beta gamma subunits, plays an important role in anchoring the G alpha subunit. The reversible and dynamic palmitoylation of the alpha subunit of stimulatory G protein (Gs alpha) has been suggested as essential for its membrane attachment. However, in our previous experiments, Gs alpha deleted in the amino terminus containing palmitoylation site, retained its binding capacity when expressed in COS cells. Thus, to evaluate the role of palmitoylation in Gs alpha membrane binding, we constructed and expressed non-palmitoylated mutants of Gs alpha and analyzed their subcellular distributions in COS-1 cells. We found that non-palmitoylated mutants of Gs alpha, C3S- and G2A/C3S Gs alpha, retained their membrane binding capacities in COS-1 cells, demonstrating that palmitoylation is not essential for membrane binding of Gs alpha in COS-1 cells. We also found that the palmitoylation did not change significantly the distribution of Gs alpha in Triton X-114 partition. These results suggest that the palmitoylation of Gs alpha may produce different effects on membrane binding depending on cell types.


Interstitial Lung Disease in Firefighters: An Emerging Occupational Hazard.
Occupational risk factors for interstitial lung disease (ILD) are a remediable aspect of this progressive pulmonary disorder. The association between firefighting and ILD is unknown. Our objective was to assess the characteristics of firefighters with ILD from a large single-center ILD registry. The University of Chicago ILD database was reviewed for patients with a history of firefighting. Clinical information was abstracted from the medical record. The prevalence rate ratio of firefighters in the database compared to the baseline prevalence of firefighting in the Chicago metropolitan area was calculated via the Poisson distribution. Nineteen firefighters were identified; all were men. A variety of ILD subtypes were seen across the cohort, including four patients with a diagnosis of connective tissue disease. Patients had mild forced vital capacity (FVC) and moderate diffusing capacity for carbon monoxide (DLCO) decrements on presentation; three patients died and two received lung transplantation over an average follow-up time of 76 months. Firefighters were seen at a greater proportion in the ILD registry than in the general population with a prevalence rate ratio of 3.98. Firefighting was overrepresented in our cohort compared to the general population, suggesting that there may be a causative association between firefighting and the presence of ILD. The wide variety of ILD subtypes observed suggest that all ILD patients should be asked about their occupational history. Further investigation to identify occupational exposures and determine the benefit of remediation is needed.


Reversible coma secondary to cefepime neurotoxicity.
To describe a case of cefepime neurotoxicity associated with acute renal failure that resulted in nonconvulsive status epilepticus. A 66-year-old woman with acute myeloid leukemia had fever on the third day of the initial chemotherapy cycle. Empiric antibiotic treatment with cefepime 2 g every 8 hours was started; fluconazole and vancomycin were subsequently added due to the persistence of fever. Ten days after initiation of cefepime, the patient developed acute renal failure followed by altered consciousness (Glasgow coma scale 6) associated with nonconvulsive status epilepticus. Cefepime was discontinued. Epileptiform activity in the electroencephalogram disappeared with clonazepam, and the patient regained consciousness 48 hours after cefepime withdrawal. Acute renal impairment combined with the use of cefepime may account for nonconvulsive status epilepticus. An objective causality assessment revealed that the adverse event was probably due to cefepime. Cefepime's neurotoxic effects derive from high serum concentrations resulting from decreased renal clearance, increased unbound antibiotic, and blood-brain barrier dysfunction during uremia. The combination of cefepime treatment and acute renal failure may induce drug-related neurotoxicity. Nonconvulsive status epilepticus frequently passes unnoticed in severely ill patients without a history of epilepsy. This disorder should be included in the list of potential causes of coma. In this patient, early detection of nonconvulsive status epilepticus and withdrawal of the antibiotic resulted in full recovery.


Involvement of synovial matrix degradation and angiogenesis in oxidative stress-exposed degenerative rotator cuff tears with osteoarthritis.
Shoulder osteoarthritis is a gradual wearing of the articular cartilage concomitant with degenerative rotator cuff tears (RCTs). This pathologic disorder is related to inflammation, oxidative stress, and angiogenesis. Degenerative alterations may prompt production of cytokines and angiogenesis-related proteins, evoking rotator cuff diseases. This study tested the hypothesis that oxidative stress-responsive mediators can influence joint inflammation of patients with RCT. Twelve healthy RCT patients not suffering shoulder osteoarthritis were categorized as the control group, and 24 patients were allocated to 2 RCT groups (RCTP1 and RCTP2), according to severity of RCT and glenohumeral arthritis. Cytokines, growth factors, and angiogenic biomarkers in synovial fluids, blood, platelet-rich plasma (PRP), and tendon tissues were analyzed with enzyme-linked immunosorbent assay, immunoblotting, and collagen zymography. Induction of interleukin 8, tumor necrosis factor α, and interleukin 1β was considerably elevated in synovial fluids of RCTP groups (P = .0398, P = .0428, P = .0828, respectively). The joint inflammation highly enhanced insulin-like growth factor 1 and transforming growth factor β1 (TGF-β1) in the synovial fluids and serum. Angiogenesis-related angiopoietin (Ang) 1 and 2, Tie-2, and hypoxia-inducible factor 1α were upregulated in reactive oxygen species-exposed RCTP synovium (P < .05). The production of matrix metalloproteinase 1 markedly increased in synovial fluids of the RCTP group (P = .043), whereas tissue collagen type I expression diminished with reduction of connective tissue growth factor expression (P = .032). Although the secretion of platelet-derived growth factor AB and vascular endothelial growth factor was marginal in the circulation (P = .714, P = .335), platelet-derived growth factor AB, TGF-β1, Ang-1, and matrix metalloproteinase 1 were enriched in PRP of the RCTP group (P < .001, P = .002, P = .0389, respectively). Synovial matrix degradation and oxidative stress-triggered angiogenesis may be involved in inducing RCT with joint inflammation. TGF-β1, Ang-1, and Ang-2 are the major components to repair RCT and to alleviate joint inflammation in PRP therapy.


Escherichia coli Strains from Patients with Inflammatory Bowel Diseases have Disease-specific Genomic Adaptations.
Escherichia coli is over-abundant in the gut microbiome of patients with inflammatory bowel disease [IBD]. Here, we aimed to identify IBD-specific genomic functions of diverse E. coli lineages. We investigated E. coli genomes from patients with ulcerative colitis [UC], Crohn's disease [CD] or a pouch, and healthy subjects. The majority of genomes were reconstructed from metagenomic samples, including newly sequenced faecal metagenomes. Clinical metadata were collected. Functional analysis at the gene and mutation level were performed and integrated with IBD phenotypes and biomarkers. Overall, 530 E. coli genomes were analysed. The E. coli B2 lineage was more prevalent in UC compared with other IBD phenotypes. Genomic metabolic capacities varied across E. coli lineages and IBD phenotypes. Host mucin utilisation enzymes were present in a single lineage and depleted in patients with a pouch, whereas those involved in inulin hydrolysis were enriched in patients with a pouch. E. coli strains from patients with UC were twice as likely to encode the genotoxic molecule colibactin than strains from patients with CD or a pouch. Strikingly, patients with a pouch showed the highest inferred E. coli growth rates, even in the presence of antibiotics. Faecal calprotectin did not correlate with the relative abundance of E. coli. Finally, we identified multiple IBD-specific non-synonymous mutations in E. coli genes encoding for bacterial cell envelope components. Comparative genomics indicates that E. coli is a commensal species adapted to the overactive mucosal immune milieu in IBD, rather than causing it. Our results reveal mutations that may lead to attenuated antigenicity in some E. coli strains.


Clinical characteristics and oncological outcomes of testicular cancer patients registered in 2005 and 2008: the first large-scale study from the Cancer Registration Committee of the Japanese Urological Association.
To describe the clinical and pathological characteristics and oncological outcomes of testicular cancer diagnosed in Japan, we report the results of the testicular cancer registration carried out by the Japanese Urological Association. Testicular cancer survey was conducted by the Japanese Urological Association in 2011 to register newly diagnosed testicular cancers in 2005 and 2008. The survey included details such as age, presenting symptoms, physical examination findings, tumor markers, histopathology, clinical stage, initial treatment and clinical outcomes. We analyzed 1121 cases of testicular primary germ cell tumor among 1157 registered patients. The median age was 37.0 years. Seminomas and non-seminomatous germ cell tumors accounted for 61.9% and 38.1%, respectively. Measurements of tumor markers were documented in 98.6% of the patients; however, there was an unsatisfactory uniform measurement of human chorionic gonadotropin, which made it difficult to evaluate the International Germ Cell Consensus Classification in all patients. The 1- and 3-year overall survival rates from the entire cohort were 98.3% and 96.8%, respectively. According to the International Germ Cell Consensus Classification, 3-year overall survival rates in the good, intermediate, and poor prognosis group were 99.1%, 100% and 79.9%, respectively. The present report is the first large-scale study of the characteristics and survival of testicular cancer patients in Japan based on multi-institutional registry data, and showed a good prognosis even in an advanced stage. The improved survival attributed substantially to accurate diagnosis and effective multimodal treatment.


Genomes of fungi and relatives reveal delayed loss of ancestral gene families and evolution of key fungal traits.
Fungi are ecologically important heterotrophs that have radiated into most niches on Earth and fulfil key ecological services. Despite intense interest in their origins, major genomic trends of their evolutionary route from a unicellular opisthokont ancestor to derived multicellular fungi remain poorly known. Here we provide a highly resolved genome-wide catalogue of gene family changes across fungal evolution inferred from the genomes of 123 fungi and relatives. We show that a dominant trend in early fungal evolution has been the gradual shedding of protist genes and the punctuated emergence of innovation by two main gene duplication events. We find that the gene content of non-Dikarya fungi resembles that of unicellular opisthokonts in many respects, owing to the conservation of protist genes in their genomes. The most rapidly duplicating gene groups included extracellular proteins and transcription factors, as well as ones linked to the coordination of nutrient uptake with growth, highlighting the transition to a sessile osmotrophic feeding strategy and subsequent lifestyle evolution as important elements of early fungal history. These results suggest that the genomes of pre-fungal ancestors evolved into the typical filamentous fungal genome by a combination of gradual gene loss, turnover and several large duplication events rather than by abrupt changes. Consequently, the taxonomically defined Fungi represents a genomically non-uniform assemblage of species.


An unusual lipid in the human pathogenic fungus Epidermophyton floccosum.
The dermatophyte Epidermophyton floccosum contains an unusual lipid characterized as 1(3),2-diacylglyceryl-3(1)-O-4'-(N,N,N-trimethyl)homoserine. Its concentration in E. floccosum is approx. 15% of the polar lipids. The role of this lipid in the biosynthesis of polar lipids and fatty acids is not yet known. However, it is interesting from a chemotaxonomic viewpoint that the lipids from two other genera of dermatophyte, Microsporum cookei and Trichophyton rubrum do not contain this novel lipid.


A Quality Control Study of the Adherence to Recommended Physiological Targets for the Management of Brain-Dead Organ Donors in South Australian Intensive Care Units.
The Australian and New Zealand Intensive Care Society and the Australasian Transplant Coordinators Association provide recommendations on the physiological management of brain-dead donors. How often physiological targets are prescribed for brain-dead donors in Australian intensive care units (ICUs), and how well these compare to recommended targets is unknown. It is also unknown how often recommended targets are achieved, irrespective of prescribed targets. We performed a retrospective, observational quality control study in 81 adult (>18 years) brain-dead donors to describe how often physiological targets were prescribed, comparing these to current guidelines. We determined the proportion of observations within the recommended target range, irrespective of any prescribed target. We aimed to identify poor adherence to recommended targets to guide future quality improvement initiatives. Seventy-four (91%) donors had at least 1 prescribed physiological target written on the ICU chart, with a median of 2 (range 2-5), and a maximum of 13 targets. Prescribed targets appeared to adhere well with recommended targets. Most recommended physiological targets were met irrespective of any prescribed target. However, one-quarter of serum sodium observations and one-third of blood glucose levels were above the recommended target. Quality improvement initiatives are required to improve the prescription of physiological targets in brain-dead donors in South Australia. Serum sodium and serum glucose targets were not met. However, this most likely reflects the need for current guidelines to be updated in line with current evidence.


Circadian clock function in Arabidopsis thaliana: time beyond transcription.
The past decade has seen a remarkable advance in our understanding of the plant circadian system, mostly in Arabidopsis thaliana. It is now well established that Arabidopsis clock genes and their protein products operate through autoregulatory feedback loops that promote rhythmic oscillations in cellular, metabolic and physiological activities. This article reviews recent studies that have provided evidence for new mechanisms of clock organization and function. These mechanisms include protein-protein interactions and the regulation of protein stability, which, together, directly connect light signalling to the Arabidopsis circadian system. Evidence of rhythmic changes in chromatin structure has also opened new and exciting ways for regulation of clock gene expression. All of these mechanisms ensure an appropriate synchronization with the environment, which is crucial for successful plant growth and development.


Elastodontic treatment with oral bio-activators in young children.
Elastodontic therapy can correct bad oral habits and malocclusions in young patients by guiding jaw growth, eliminating functional disorders, and improving tooth position. The aim of this study was to assess the effects of bio-activator therapy on the presence of atypical swallowing with tongue thrust in growing patients. A retrospective study was conducted. Data regarding the early orthodontic treatment of 40 consecutive patients with atypical swallowing and tongue thrust (23 males and 17 females) were assembled from January 2019 to January 2020. All patients (≥7 and ≤15 years of age) were monitored for 1 year in a private practice in Isernia, Italy. The mean age at commencement of orthodontic treatment was 8.5 years (range=7.1-14.9 years), and the mean total duration of therapy was 1 year (range=11 months-1 year). Final lateral radiographs demonstrated a mean of improvement of 8° for upper and lower incisor proclination (I/SN) and 3.5° for incisor mandibular plane angle (IMPA) in 36 patients, and 5° of I/SN and 2° of IMPA in the remaining 4 children after 1 year of treatment. Bad oral habits in younger patients must not be ignored. The duration of treatment can differ depending on the severity of the open bite and the patient's cooperation. This study demonstrates the short-term efficacy of these myofunctional appliances in the treatment of atypical swallowing. In order to quickly eliminate factors which endanger healthy development of dento-skeletal structure, it is important to closely monitor patients during their development phase.


Robotic-assisted laparoscopic radical nephrectomy using the Da Vinci Si system: how to improve surgeon autonomy. Our step-by-step technique.
Herein, we describe several steps to improve surgeon autonomy during a Left Robotic-Assisted Laparoscopic Radical Nephrectomy (RALRN), using the Da Vinci Si system. Our kidney cancer program is based on 2 community hospitals. We use the Da Vinci Si system. Access is obtained with the following trocars: Two 8 mm robotic, one 8 mm robotic, bariatric length (arm 3), 15 mm for the assistant and 12 mm for the camera. We use curved monopolar scissors in robotic arm 1, Bipolar Maryland in arm 2, Prograsp Forceps in arm 3, and we alternate throughout the surgery with EndoWrist clip appliers and the vessel sealer. Here, we described three steps and the use of 3 robotic instruments to improve surgeon autonomy. Step 1: the lower pole of the kidney was dissected and this was retracted upwards and laterally. This maneuver was performed using the 3rd robotic arm with the Prograsp Forceps. Step 2: the monopolar scissors was replaced (robotic arm 1) with the robotic EndoWrist clip applier, 10 mm Hem-o-Lok. The renal artery and vein were controlled and transected by the main surgeon. Step 3: the superior, posterolateral dissection and all bleeders were carefully coagulated by the surgeon with the EndoWrist one vessel sealer. We have now performed 15 RALRN following these steps. Our results were: blood loss 300 cc, console time 140 min, operating room time 200 min, anesthesia time 180 min, hospital stay 2.5 days, 1 incisional hernia, pathology: (13) RCC clear cell, (1) chromophobe and (1) papillary type 1. Tumor Stage: (5) T1b, (8) T2a, (2) T2b. We provide a concise, step-by-step technique for radical nephrectomy (RN) using the Da Vinci Si robotic system that may provide more autonomy to the surgeon, while maintaining surgical outcome equivalent to standard laparoscopic RN.


Investigation of spore coat display of Bacillus subtilis β-galactosidase for developing of whole cell biocatalyst.
The production of highly efficient, recyclable and cost-effective enzymes is one of the most important goals in industrial biotechnology. Bacterial spores are highly resistant to harsh environmental conditions, easy to produce and are suitable for manipulation of genetic materials. These features make them a very efficient tool for biotechnology. Here, we show the use bacterial spores for presentation of functional enzyme. Spore coat display was used to produce a biocatalyst, which expresses β-galactiosidase (LacA). This enzyme is commonly used to produce lactose-free milk for lactose intolerant individuals. The lacA gene from Bacillus subtilis strain 168 was expressed on the surface of B. subtilis RH101(ΔcotC) spores using CotC as protein carrier. Presence of LacA protein is verified by western blotting. Results of β-galactiosidase assay show that the expressed enzyme retained its activity in condition of freezing and drying, as well as after recovery from the reaction's mixture.


The comparative study of efficacy between 1064-nm long-pulsed Nd:YAG laser and 595-nm pulsed dye laser for the treatment of acne vulgaris.
The popularity of laser therapy in acne treatment has been increasing recently due to its safety, effectiveness, and convenience. Both 595-nm pulsed dye laser (PDL) and 1064-nm long-pulsed neodymium:yttrium-aluminum-garnet laser (Nd:YAG) have been successful in treating inflammatory acne lesions. However, clinical data from controlled comparative studies are still lacking. To compare the clinical efficacy of 1064-nm Nd:YAG with 595-nm PDL for the treatment of acne vulgaris. Thirty-four participants with mild to moderate facial acne were enrolled and then randomized to receive three, 2-week interval treatments with 1064-nm Nd:YAG on one side of the face and 595-nm PDL on the other side. Clinical assessments including acne lesion counts, acne erythema grading, and erythema index were performed at baseline, 2nd, 4th, and 8th week. Participants' satisfaction, preference, and adverse effects were recorded. As compared with baseline, the significant reduction of mean inflammatory acne lesion counts, acne erythema grading, and erythema index was demonstrated on 595-nm PDL-treated sides and 1064-nm Nd:YAG-treated sides. However, there were no significant differences between both sides. The participants were satisfied with both laser treatments, but the participants preferred 1064-nm Nd:YAG over 595-nm PDL treatment. The adverse effects were less on 1064 nm Nd: YAG-treated sides. 1064-nm Nd:YAG and 595-nm PDL treatments are equally effective in reducing inflammatory acne lesions and acne erythema in mild to moderate facial acne vulgaris.


Circadian oscillation of the multiple unit activity in the guinea pig suprachiasmatic nucleus.
In the guinea pig with chronically implanted electrodes, neuronal multiple unit activity (MUA) was recorded inside and outside the suprachiasmatic nucleus (SCN). Long-term recording of the SCN indicated distinct daily rhythms with a daytime peak in MUA during a 24-h light-dark (LD 12:12) cycle. On the other hand, MUA recorded from adjacent hypothalamic regions outside the SCN showed a phase reversal with a nighttime peak, similarly to the rat. The amplitude of the rhythms recorded outside the SCN was much smaller (one-half to one-quarter) than that inside the SCN. These rhythms persisted during constant darkness indicating characteristics of endogenous circadian rhythmicity. When the external light-dark cycle was delayed abruptly for 12 h, MUA rhythms showed a gradual phase shift taking 7-10 days for complete reentrainment. Overt behavior including sleep-wakefulness did not show significant and consistent daily or circadian rhythms in spite of the distinct oscillation in neuronal activity inside the SCN.


The association between chiropractic integration in an Ontario community health centre and continued prescription opioid use for chronic non-cancer spinal pain: a sequential explanatory mixed methods study.
Emerging evidence suggests that access to chiropractic care may reduce the likelihood of initiating an opioid prescription for spinal pain; however, the impact of chiropractic care for patients already prescribed opioids is uncertain. We undertook a sequential explanatory mixed methods study to evaluate the association between initiating chiropractic care and continued opioid use among adult patients attending an Ontario community health centre (CHC) and receiving opioid therapy for chronic non-cancer spinal pain. We conducted a retrospective cohort study of 210 patient records between January 1, 2014 and December 31, 2020. We used generalized estimating equations, adjusted for patient demographics, co-morbidities, visit frequency, and calendar year, to evaluate the association between receipt versus non-receipt of chiropractic services and continued opioid use (e.g., unique opioid fills, number of refills, and dosages) up to one year following the index chiropractic visit. We also completed follow-up interviews with 14 patients and nine general practitioners from the CHC and integrated these data with our quantitative findings. Over 12-month follow-up, there were lower rates of opioid fills (incidence rate ratio [IRR] = 0.66; 95% confidence interval [CI], 0.52-0.83) and refills (IRR = 0.27; 95% CI, 0.17-0.42) among chiropractic recipients (n = 49) versus non-recipients (n = 161). Although patients who did and did not receive chiropractic care began the study with the same dose of opioids, recipients were less likely to be prescribed higher-dose opioids (i.e., ≥ 50 mg morphine equivalents daily) compared to non-recipients at three months (odds ratio [OR] = 0.14; 95% CI, 0.04-0.47), six months (OR = 0.14; 95% CI, 0.05-0.40), nine months (OR = 0.19; 95% CI, 0.07-0.57), and 12 months (OR = 0.22; 95% CI, 0.08-0.62). Interviews suggested that patient self-efficacy, limited effectiveness of opioids for chronic pain, stigma regarding use of opioids, and access to chiropractic treatment were important influencing factors. We found that continued prescription opioid use among patients with chronic non-cancer spinal pain who received chiropractic care was lower than in patients who did not receive chiropractic care. Four themes emerged in our qualitative interviews to help provide a richer understanding of this association. Randomized controlled trials are needed to establish the effect of chiropractic care on opioid use for chronic spinal pain.


Tensile strength of warm and cool season forage grasses in Florida.
The tensile strength (TS) of four warm-season and three cool-season forage grasses was measured with an Instron Universal machine, along with cell-wall analysis and determination of in vitro organic matter digestibility. The mean TS of the warm-season grasses was significantly higher than that of the cool season grasses (22 vs. 9 kg, respectively, p < .05). The concentrations of neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid detergent lignin (ADL) were significantly greater in the warm- than in the cool-season grasses (p < .05), whereas ash concentration was greater in the cool-season grasses. Among the warm-season grasses that were studied, elephant grass had the highest and bermuda grass had the lowest TS (34.4 and 14.9 kg, respectively, p < .05); Among the cool-season grasses triticale had greater TS than wheat and oats (12.6 vs. 6.8 and 7.5 kg, respectively, p < .05). TS was significantly correlated with NDF, ADF, and ADL, and negatively correlated with in vitro organic matter digestibility (correlation coefficients were 0.64, 0.73. 0.41, and -0.64, respectively). Grass tensile strength may have implications on animal preference and on the energy that animals must spend during grazing, and consequently on animal performance (feed intake, daily weight gain and milk, and meat production). Information on grass TS would help to select and screen improved forage cultivars and enable to improve grassland management with better animal performance.


The decomposition of alpha-aminophosphine oxides to phosphonic acid derivatives (PIII).
Aminophosphine oxides and aminophosphonates are, in general, very stable compounds. However, following phosphorus-carbon bond cleavage in aqueous acidic media these compounds sometimes decompose to phosphonic acids derivatives (P(III)). Despite some controversy in the literature, careful analysis supported by theoretical studies leads to the conclusion that decomposition to P(III) derivatives proceeds via an elimination reaction.


Frequency of ubiquitous connectivity and associated factors among Mexican adolescents.
There is limited information in Mexico - a middle-income country and a digital adopter with an important demographic bonus - regarding the potential use of technology and connectivity in health promotion among adolescent population. Therefore, the objective of this study was to determine the proportion of adolescents connected ubiquitously; and to identify its associated factors for the further development of mobile health interventions. An online survey of adolescents from state of Morelos, Mexico, was conducted in 2016. Explored individual socio-educational and school technological infrastructure characteristics and habits of use of mobile technologies. A logistic regression model was fitted to identify variables associated with ubiquitous connectivity. One thousand three hundred thirty-six students were included and six questionnaires (0.45%) were eliminated due to duplication of information. Fifty-four percent of participants were female, and the mean age was 16.31 ± 0.84 years. In total, 47% of students were ubiquitously connected. Associated factors to ubiquitous connectivity included better academic performance, the need to use Internet-based technologies, engaging in ludic activities on the Web and living in the state capital. Ubiquitous connectivity it's a desirable condition for strengthening health promotion programs focused on young population. Strategies including digital technology tools with potential to increase adolescent engagement should be explored and evaluated. However, it is necessary to recognize that there are additional factors that may influence the success of health promotion interventions.


Possible involvement of inflammatory/reparative processes in the development of uterine fibroids.
Uterine leiomyomas are benign tumors in the smooth muscle layer of the uterus. The most common histological type is the "usual leiomyoma", characterized by overexpression of ECM proteins, whereas the "cellular type" has higher cellular content. Our objective is to investigate the involvement of inflammatory and reparative processes in leiomyoma pathobiology. Using a morphological approach, we investigate the presence of inflammatory cells. Next, we determine the localization of the ECM, the presence/absence of fibrotic cells via α-sma and desmin and the immunohistochemical profile of the mesenchymal cells with respect to CD34. Finally, we explore the effect of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-15, GM-CSF and IFN-γ) on pro-fibrotic factor activin A mRNA expression in vitro. Higher numbers of macrophages were found inside and close to leiomyomas as compared to the more distant myometrium. Cellular leiomyomas showed more macrophages and mast cells than the "usual type". Inside the fibroid tissue, we found cells positive for α-sma, but negative for desmin and a large amount of collagen surrounding the nodule, suggestive of myofibroblasts producing ECM. In the myometrium and leiomyomas of the "usual type", we identified numerous CD34+ fibroblasts, which are known to give rise to myofibroblasts upon loss of CD34 expression. In leiomyomas of the "cellular type", stromal fibroblasts were CD34-negative. Finally, we found that TNF-α increased activin A mRNA in myometrial and leiomyoma cells. In conclusion, this study demonstrates the presence of inflammatory cells in uterine leiomyomas, which may contribute to excessive ECM production, tissue remodeling and leiomyoma growth.


Isolation of a new thermohalophilic Thermus thermophilus strain from hot spring, able to grow on a renewable source of polysaccharide.
A thermohalophilic strain, Samu-Sal, isolated from hot springs of the Mount Grillo (Baia, Naples, Italy) at a depth of 60 m, according to its genotypic analyses is related to Thermus genus and should be classified as a new strain of Thermus thermophilus. Strain Samu-SA1 grew using, as sole carbon source, a polysaccharide extracted from waste industrial tomato process with a yield of 3.5 g l(-1). Strain Samu-SA1 synthesized several alpha- and beta-glycosidases.


Characterization of Salmonella spp. isolated from chickens in Central China.
Salmonella is an important zoonotic pathogen, and chickens are one of its main hosts. Every year, Salmonella infections pose a serious threat to the poultry industry in developing countries, especially China. In this study, a total of 84 Salmonella isolates recovered from sick and healthy-looking chickens in central China were characterized by serotyping, MLST-based strain typing, presence of potential virulence factors, and antimicrobial resistance profiles. Data showed that the main serotypes of Salmonella isolates in central China were Salmonella enterica serovar Gallinarum biovar Pullorum, Salmonella enterica serovar Gallinarum biovar Gallinarum, Salmonella enterica serovar Enteritidis and Salmonella enterica serovar Typhimurium, and among them, S. Pullorum was the dominant type in both sick and healthy-looking chickens, accounting for 43.9 and 46.5%, respectively, while S. Enteritidis was only found in healthy-looking chickens. All isolates exhibited higher resistance rates to ampicillin (97.6%), tetracycline (58.3%) and colistin (51.2%), and among these isolates, 49.5% were resistant to more than three drugs in different combinations. S. Enteritidis was the most severe multidrug-resistant serotype, which showed higher resistance rates to colistin, meropenem and ciprofloxacin. Multilocus sequence typing (MLST) revealed that S. Gallinarum and S. Enteritidis isolates were clustered in clade 1, which belonged to two and one STs, respectively. All S. Typhimurium isolates were clustered in clade 3, and belonged to three STs. However, S. Pullorum were distributed in three clades, which belonged to 7 STs. Twenty-seven virulence-associated genes were detected, and expected cdtB, which was absent in all the isolates, the other 26 genes were conserved in the closely related Salmonella serogroup D (S. Enteritidis, S. Pullorum, and S. Gallinarum). Salmonella serogroup D was the major subgroup, and S. Pullorum was the most common type in sick and healthy-looking chickens in central China. Drug resistance assays showed serious multiple antimicrobial resistances, and S. Enteritidis was the most severe drug-resistant serotype. MLST showed that there was correlation between serotypes and genotypes in most Salmonella isolates, except S. Pullorum, which showed complicated genetic diversity firstly. These results provide important epidemiological information for us to control Salmonella in chickens.


General practice reform in the United Kingdom: moving into the new millennium.
Radical reform of general practice is under way in the United Kingdom, driven by a National Health Service "modernisation" agenda and the promise of additional resources from the Blair Government. Australian GPs can not afford to ignore these changes and should ensure that through their representative bodies they influence any similar changes in Australia.


Transport of brain-derived neurotrophic factor across the blood-brain barrier.
Brain-derived neurotrophic factor (BDNF) is a potential therapeutic agent for degenerative disorders of the central nervous system. In this report, we investigated the ability of BDNF to cross the blood-brain barrier (BBB). BDNF was stable in blood up to 60 min after i.v. injection, with evidence for aggregation, and had an early, rapid influx into brain. By 10 min, most of the BDNF sequestered by the cerebral cortex was associated with the parenchyma rather than with the endothelial cells, demonstrating complete passage across the BBB. A small dose of unlabeled BDNF enhanced the entry of 125I-BDNF from blood to brain after an i.v. bolus injection, whereas larger doses had no effect. In contrast, a large dose of unlabeled BDNF inhibited the influx of 125I-BDNF during in situ brain perfusion. After intracerebroventricular injection, the efflux of BDNF from brain to blood occurred at a rate similar to that for reabsorption of cerebrospinal fluid, and no evidence for self-inhibition was found. Therefore, we conclude that intact BDNF in the peripheral circulation crosses the BBB by a high-capacity, saturable transport system.


Folding and stability of the leucine-rich repeat domain of internalin B from Listeri monocytogenes.
Internalin B (InlB), a surface protein of the human pathogen Listeria monocytogenes, promotes invasion into various host cell types by inducing phagocytosis of the entire bacterium. The N-terminal half of InlB (residues 36-321, InlB321), which is sufficient for this process, contains a central leucine-rich repeat (LRR) domain that is flanked by a small alpha-helical cap and an immunoglobulin (Ig)-like domain. Here we investigated the spectroscopic properties, stability and folding of InlB321 and of a shorter variant lacking the Ig-like domain (InlB248). The circular dichroism spectra of both protein variants in the far ultraviolet region are very similar, with a characteristic minimum found at approximately 200 nm, possibly resulting from the high 3(10)-helical content in the LRR domain. Upon addition of chemical denaturants, both variants unfold in single transitions with unusually high cooperativity that are fully reversible and best described by two-state equilibria. The free energies of GdmCl-induced unfolding determined from transitions at 20 degrees C are 9.9(+/-0.8)kcal/mol for InlB321 and 5.4(+/-0.4)kcal/mol for InlB248. InlB321 is also more stable against thermal denaturation, as observed by scanning calorimetry. This suggests, that the Ig-like domain, which presumably does not directly interact with the host cell receptor during bacterial invasion, plays a critical role for the in vivo stability of InlB.


Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of inflammatory bowel disease.
4-1BB (CDw 137), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a costimulatory receptor primarily expressed on activated T cells. It has been shown that the administration of agonistic anti-4-1BB monoclonal antibody (mAb) enhances tumor immunity and allogenic immune responses. Paradoxically, we found that the administration of anti-4-1BB mAb reduced the incidence and severity of inflammatory bowel disease. In this study, we investigated the effects of anti-4-1BB mAb in a murine intestinal inflammation model, which induced by the hapten reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS) and mimics immunologic characteristics of human Crohn's disease (CD). Colitis was induced by rectal administration of 2mg of TNBS in 35% ethanol using a vinyl catheter positioned 4cm from the anus. All mice were sacrificed 3 and 10 days after the TNBS administration. The disease activity index (DAI), histological changes of the colon and production of cytokines (IL-2, IL-4, IL-10 and IFN-gamma) were evaluated. The surface molecules of T cells in peripheral blood, spleen and mesenteric lymph nodes were analyzed by flow cytometry. When mice were treated with anti-4-1BB mAb, improvement in both wasting and histopathologic signs of colonic inflammation was observed. The increase a number of splenic CD4(+)CD25(+) T cells and decreased synthesis of the Th1 cytokine IL-2 also occurred. Interestingly, increased production of Th1 cytokine IFN-gamma and proportion of CD8(+) T cells were observed in mice treated with anti-4-1BB mAb in comparison to the colitic mice. These studies show, for the first time, that agonistic anti-4-1BB mAb can improve experimental colitis by reduction of IL-2 and augmentation of CD4(+)CD25(+) regulatory T cells. TNBS colitis is Th1-mediated and has similar histologic features and distribution of inflammation to CD. This study suggests that anti-4-1BB mAb therapy could be effective in the treatment of patients with CD.


Surgical management of a giant hepatic metastasis from a cranial meningioma 10 years after resection.
Meningiomas are the most common type of primary brain tumor; they have a low risk for extracranial metastases, which are primarily associated with increased tumor grade. Hepatic metastases from cranial meningiomas are extremely rare, with only a paucity of cases reported in the literature and no standardized approach to management. Herein, we report a case of an incidentally discovered giant (>20 cm) metastatic meningioma to the liver treated with surgical resection 10 years following resection of a low-grade cranial meningioma. This report also highlights the use of (68Ga) DOTATATE PET/CT as the diagnostic imaging modality of choice when evaluating for meningioma metastases. To our knowledge, this report describes the largest hepatic metastasis from a cranial meningioma to undergo surgical resection in the literature.


Molecular changes in thyroid neoplasia.
All authors integrating the known facts into a model of thyroid carcinogenesis concur that two main histotypes of thyroid cancer exhibit different routes of molecular development. RET rearrangements are an initiating event in papillary carcinoma, and simultaneously the most characteristic mutation for this type of cancer. They are followed by further, not well recognized, mutations. RAS mutations are regarded as a crucial event in the development of follicular tumors already at the adenoma step, while in papillary cancer they belong to the spectrum of secondary mutations, enabling tumor progression. Aberrant DNA methylation, causing loss of P16 tumor supressor gene, may be a common event in both types of cancer. Aneuploidy is seen much more frequently in follicular than in papillary cancer, which also exhibits a low rate for loss of heterozygosity and microsatellite instability. Mutations of the P53 tumor supressor gene are a common feature of undifferentiated thyroid cancers and could be responsible for their aggressive phenotype. RET rearrangements have been proposed as identifying fingerprints for irradiation induced thyroid cancer in children. Our own data speak against this hypothesis. We noted a high frequency of RET/PTC3 mutations in a group of Polish children with papillary thyroid carcinoma, regarded as sporadic cancer.


Evaluating the theoretical performance of aircraft wastewater monitoring as a tool for SARS-CoV-2 surveillance.
Air travel plays an important role in the cross-border spread of infectious diseases. During the SARS-CoV-2 pandemic many countries introduced strict border testing protocols to monitor the incursion of the virus. However, high implementation costs and significant inconvenience to passengers have led public health authorities to consider alternative methods of disease surveillance at borders. Aircraft wastewater monitoring has been proposed as one such alternative. In this paper we assess the theoretical limits of aircraft wastewater monitoring and compare its performance to post-arrival border screening approaches. Using an infectious disease model, we simulate an unmitigated SARS-CoV-2 epidemic originating in a seed country and spreading to the United Kingdom (UK) through daily flights. We use a probabilistic approach to estimate the time of first detection in the UK in aircraft wastewater and respiratory swab screening. Across a broad range of model parameters, our analysis indicates that the median time between the first incursion and detection in wastewater would be approximately 17 days (IQR: 7-28 days), resulting in a median of 25 cumulative cases (IQR: 6-84 cases) in the UK at the point of detection. Comparisons to respiratory swab screening suggest that aircraft wastewater monitoring is as effective as random screening of 20% of passengers at the border, using a test with 95% sensitivity. For testing regimes with sensitivity of 85% or less, the required coverage to outperform wastewater monitoring increases to 30%. Analysis of other model parameters suggests that wastewater monitoring is most effective when used on long-haul flights where probability of defecation is above 30%, and when the target pathogen has high faecal shedding rates and reasonable detectability in wastewater. These results demonstrate the potential use cases of aircraft wastewater monitoring and its utility in a wider system of public health surveillance.


Increased densities of binding sites for the 'peripheral-type' benzodiazepine receptor ligand [3H]PK 11195 in rat brain following portacaval anastomosis.
Using quantitative receptor radioautography, binding sites for the 'peripheral-type' benzodiazepine receptor ligand [3H]PK 11195 were studied in rats 4 week after end-to-side portacaval anastomosis and in sham-operated controls. Portacaval anastomosis resulted in region-selective increases in density of [3H]PK 11195 binding sites in cerebellum, pons greater than thalamus, cerebral cortex greater than hippocampus greater than striatum. Possible mechanisms implicated in these changes include (i) the action of endogenous ligands for the mitochondrial benzodiazepine receptor such as octadecaneuropeptide and (ii) neurotoxic actions of ammonia. In view of the proposed role of these receptors as modulators of intermediary metabolism and neurosteroid biosynthesis, such changes could contribute to the neurochemical mechanisms responsible for portal-systemic encephalopathy.


Neuroprotective effect of activated 5'-adenosine monophosphate-activated protein kinase on cone system function during retinal inflammation.
Retinal inflammation can cause retinal neural disorders. In particular, functional disorder in the cone photoreceptor system influences visual acuity. However, the underlying mechanism is not yet fully understood. In this study, we evaluated cone system function and the role of 5'-adenosine monophosphate-activated protein kinase (AMPK) during retinal inflammation. Six to eight-week-old male C57BL/6 mice received an intraperitoneal injection of lipopolysaccharide (LPS) to induce retinal inflammation, and were treated with an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR; 250 mg/kg body weight) or phosphate-buffered saline as vehicle 3 h before the LPS injection. The b-wave of the photopic electroretinogram, which represents cone system function, was decreased 24 h after LPS injection and this reduction was suppressed by AICAR treatment. At this time point, there was no remarkable morphological change in the cone photoreceptor cells. At 1.5 h after LPS injection, the retina mRNA levels of an inflammatory cytokine, Tnf-α, were increased, and those of a regulator of mitochondrial biogenesis, Pgc1-α, were decreased. However, AICAR treatment suppressed these changes in mRNA expression. Immunohistochemistry showed that induction of glial fibrillary acidic protein expression was also suppressed by AICAR 24 h after LPS injection. Furthermore, the mouse cone photoreceptor-derived cell line 661W was treated with AICAR to increase the level of phosphorylated and activated AMPK. After 3 h of AICAR incubation, 661W cells showed decreased Tnf-α mRNA levels and increased Pgc1-α mRNA levels. AMPK activation has a neuroprotective effect on cone system function during inflammation, and the effect may, at least in part, involve the regulation of inflammatory cytokines and mitochondrial condition.


An analysis of the costs and benefits of physiological integration between ramets in the clonal perennial herb Glechoma hederacea.
The costs and benefits, measured in terms of dry weight, of physiological integration between clonal ramets, were analysed in two experiments conducted on the clonal herb Glechoma hederacea. Firstly, integration between consecutively-produced ramets was examined in an experiment in which stolons grew from one set of growing conditions (either unshaded or shaded and either nutrient-rich or nutrient-poor) into conditions in which light or nutrient level was altered. Comparisons were made between the dry weight of the parts of the clones produced before and after growing conditions were changed, and the dry weights of the corresponding part of control clones subjected to constant growing conditions. In a second experiment, integration between two distinct parts of G. hederacea clones was investigated. In this experiment clones were grown from two connected parent ramets and the parts of the clone produced by each parent ramet were subjected independently to either nutrient-rich or nutrient-poor conditions. Ramets in resource-rich conditions provided considerable physiological support to those in resource-poor conditions. This was measured as a dry weight gain compared with the weight of the corresponding part of the control clones growing in resource-poor conditions. However, when stolons grew from resource-poor conditions into resource-rich conditions, there was no similar evidence of the resourcepoor ramtes receiving support from resource-rich ramets. Physiological integration did not result in dry weight gains when this would have necessitated basipetal translocation of resources.Because of the predominantly acropedal direction of movement of translocates in G. hederacea, the structure of the clone was important in determining the effectiveness of integration between ramets. Where physiological integration was effective, the cost to the supporting ramets in terms of dry weight was insignificant. Physiological integration allows clones to maintain a presence in less favourable sites with insignificant cost to ramets in favourable sites, thereby reducing the probability of invasion by other plants, and providing the potential for rapid clonal growth if conditions improve. Integrated support of ramets in unfavourable conditions also enables the clone to grow through unfavourable sites, thus increasing the probability of encountering more favourable conditions by wider foraging.


Home exercise in the dart-throwing motion plane after distal radius fractures: A pilot randomized controlled trial.
During daily functions, our wrist moves through an oblique plane, named the dart-throwing motion (DTM) plane. This plane is considered a more stable plane because the proximal carpal row remains relatively immobile. However, rehabilitation programs that incorporate exercising in the DTM plane have yet to be explored. The purpose of this study was to evaluate the rehabilitation outcomes after treatment in the DTM plane compared with outcomes after treatment in the sagittal plane after distal radius fracture. This is a pilot randomized controlled trial. Subjects after open reduction internal fixation were assigned into a research group (N = 12; ages 48.7 ± 7.3) and a control group (N = 12; ages 50.8 ± 15). The control group activated the wrist in the sagittal plane, whereas the research group activated the wrist in the DTM plane. Range of motion, pain levels, functional hand motor skills tests, and satisfaction from self-training exercise were measured before and after a 12-session intervention. The outcome measures were similar between the treatment groups. The research group reported significantly higher satisfaction rates than the control group on topics such as general satisfaction (research group: 3.4 ± 0.7, control group: 2. 5 ± 1.2, P = .030), motivation to exert oneself (research group: 2.8 ± 1.0, control group: 2.3 ± 1.2, P = .009), progressed function (research group: 3.4 ± 0.7, control group: 2.4 ± 1.1, P = .012), and self-training contribution to the daily function (research group: 3.4 ± 0.7, control group: 2.5 ± 1.2, P = .030). Pilot results do not favor one treatment method over the other. However, exercising in the DTM plane may contribute to the satisfaction of the client and increase self-training motivation.


Small interfering RNA based knock down of acute heat shock and or GGA inducible bovine heat shock protein 70 may interfere invitro expression pattern of TLR2/4 and NOD1/2.
Heat shock protein 70 (Hsp70) is a widely known mammalian stress-inducible protein critical for cytoprotection against different stressors. Despite the chaperone based cytoprotective functions, intracellular Hsp70 also participates in diverse immune modulatory activities. To investigate the immune modulatory effect of inducible bovine Hsp70, we examined the expression profile of four major pattern recognition receptors (PRRs) viz. TLR2/4 and NOD1/2 using two different invitro cell cultured models. We observed that, invitro acute heat stress and Geranylgeranylacetone (GGA) induction increased the level of Hsp70 which upregulated the expression of all the four PRRs in both the cell cultured models. However, the expression level of TLR4 was found to be highest followed by NOD2, TLR2 and NOD1. Conversely, specific siRNA based knockdown of Hsp70 showed a decreased expression level of all the four PRRs. This study may add some references pertaining to the innate immune modulatory effects of bovine heat shock protein 70.


Primary and secondary prevention of drink driving by the use of alcolock device and program: Swedish experiences.
To prevent drinking and driving, alcolock (or alcohol-interlock) devices and programs were introduced in Sweden in 1999. Two types of prevention programs were begun. A primary prevention strategy was initiated to prevent alcohol impaired driving by individuals not pre-selected for having prior DWI offences. This approach was first applied as a pilot project in three commercial transport companies (buses, trucks, taxis). Also a secondary prevention trial was begun as a voluntary 2-year program for DWI offenders involving strict medical requirements, including counseling and regular checkups by a medical doctor. The program did not require a prior period of hard suspension and focused on changing alcohol use habits. Alcolocks in commercial vehicles have been well accepted by professional drivers, their employers, and their passengers, and the number of vehicles with alcolocks as a primary prevention measure is rapidly growing in Sweden. Three of 1000 starts in the primary prevention program were blocked by the alcolock after measuring a BAC higher than the legal limit and lock point of 0.02% (20mg/dl). Only 11% of eligible DWI offenders took part in the voluntary, secondary prevention program. Of these, 60% had diagnoses of alcohol dependence or abuse. During the program, alcohol consumption generally decreased significantly as measured through five biological alcohol markers, and the rate of DWI recidivism fell sharply from a yearly rate of approximately 5% to almost 0. These effects on DWI recidivism are paralleled by reduced rates of police-reported traffic accidents involving injuries and hospital admissions due to road accidents. Successful completion of the program appears to have lasting effects (even 2.5 years later) in terms of far lower rates of DWI recidivism and maybe also lower crash rates. On the other hand those being dismissed from the program appear to rapidly return to previous behaviour. Hard suspension seems almost to have an adverse effect on DWI recidivism, but crashes resulting in injuries may be reduced during revocation.


Lipid lowering effects of Momordica charantia (Bitter Melon) in HIV-1-protease inhibitor-treated human hepatoma cells, HepG2.
1. Hyperlipidemic effects of HIV-1-protease inhibitors (PI) are associated with increased hepatic production of triglyceride (TG)-rich lipoproteins, rather than lipoprotein clearance. PI are known to increase apolipoprotein B (apoB) secretion, apoC-III mRNA expression and decrease apoA-1 secretion. Nutritional therapy remains an important strategy to manage PI-associated hyperlipidemia. 2. This study investigated the in vitro efficacy of Asian vegetable, Momordica charantia or bitter melon (BM) to ameliorate PI-associated apoB and lipid abnormalities in HepG2 cells. 3. Our study demonstrates that bitter melon juice (BMJ) significantly reduced apoB secretion and apoC-III mRNA expression and normalized apoA-I expression in PI-treated HepG2 cells. BMJ also significantly reduced cellular TG and microsomal TG transfer protein, suggesting that lipid bioavailability and lipidation of apoB assembly may play a role in decreased apoB secretion. 4. Identifying molecular targets of BM may offer alternative dietary strategies to decrease PI-associated hyperlipidemia and improve quality of life among HIV-1-infected patients.


The influence of topical corticosteroid therapy upon polymorphonuclear leukocyte distribution, vascular integrity and ascorbate levels in endotoxin-induced inflammation of the rabbit eye.
An acute inflammatory response was initiated in the rabbit eye by an intravitreal injection of bacterial endotoxin. We examined the effect of topical corticosteroid therapy upon polymorphonuclear leukocyte (PMN) infiltration into the eye, protein leakage into aqueous humor and ascorbate level in aqueous humor. Corticosteroid therapy initiated prior to injection of endotoxin suppresses the clinical signs of inflammation, partially prevents the fall in aqueous-humor ascorbate level, has little effect upon protein leakage, but markedly reduces PMN infiltration. Corticosteroid therapy initiated after the injection of endotoxin also suppresses the clinical signs of inflammation, reduces the fall in ascorbate levels and does not influence protein leakage. However, in this case there is a marked persistence of PMN infiltration into ocular tissues. Thus the number of PMNs present in the ocular tissues is little different from that in non-steroid treated control eyes, although the clinical signs of inflammation are reduced. We suggest that in the clinical situation, the initial anti-inflammatory activity of the corticosteroids is related to an inhibitory effect upon the activity of PMNs already within the tissues, which then prevents the ensuing cascade of characteristic inflammatory events.


Epstein-Barr virus negative smooth muscle neoplasm of the stomach in a young woman.
Gastric smooth muscle neoplasms are rare and poorly investigated malignancies. Their importance relies on differential diagnosis with more frequent neoplasms(e.g. GIST), on their often mild and deceitful clinical presentation and on their heterogeneous outcome. Moreover, the pathogenesis of gastric leiomyosarcoma seems to point to some acknowledged oncogenic factors such as radiations or oncogenic viral infections. Herein, we describe a case of metastatic gastric leiomyosarcoma in a young woman, previously diagnosed with acute lymphoblastic leukemia treated with chemoradiotherapy.


Mapping of [3H]vasopressin binding sites in the brain of jerboa (Jaculus orientalis) by an high resolution beta-radio imager.
The distribution of vasopressin receptors in the brain of the jerboa (Jaculus orientalis) was studied using tritiated arginin vasopressin ([3H]vasopressin). beta-Particles emitted from tritiated ligand bound to brain sections were detected by a newly developed beta-radio imager to generate a light spot which was read by a charge coupled device camera. The number and coordinate of the center of gravity of the light spot were recorded. After summation in pixels of the counts collected during 2-20 h, an image was produced representing the distribution of [3H]vasopressin bound to brain sections. Specific vasopressin binding was detected in various brain regions such as the cerebral cortex, islands of Calleja, pallidum, amygdala and the hippocampus as well as in the pituitary gland. The intensity of the binding was quantified directly from the images obtained and expressed in decays/min/surface unit. The linearity of this method of detection allowed a relevant measurement of non-specific binding, therefore its subtraction from images representing the total binding. Three-dimensional reconstructions of labeled structures were also performed. The presence of numerous vasopressin receptors in the jerboa hippocampus suggests a major role for this neuropeptide in this part of the brain.


[Abdominal compartment syndrome and acute intestinal distress syndrome].
Seriously ill patients frequently present intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) as complications, and the associated mortality is very high. This review offers an update on the most controversial aspects of these entities: factors favoring their appearance, the most common causes, prognosis, and methods of measuring intra-abdominal pressure (IAP), physiopathological consequences in relation to the different organs and systems, and the currently accepted treatment measures (medical and/or surgical). Simultaneously to the strictly physical mechanisms of injury, such as direct compression of intra-abdominal organs and vessels, the transmission of IAP to other compartments, and the drop in cardiac output, a series of immune-inflammatory mediators generated in the intestine itself may also intervene. Hypoperfusion, sustained ischemia and the ischemia-reperfusion phenomenon, would act upon the microbiota, intestinal epithelium and intestinal immune system, triggering a systemic inflammatory response and multiorgan dysfunction that appears in the final stages of ACS.


[Diagnostic value of IgG subtypes in membranous nephropathy: A case report].
The study of immunoglobulin G subtypes constituting immune deposits present in membranous nephropathy is useful to guide diagnosis. IgG4 deposits are more often seen in primitive forms of membranous nephropathy due to autoantibody (anti-phospholipase A2 receptor in a majority of cases). These deposits are polytypic. In secondary forms, deposits are constituted of IgG1, IgG2 and IgG3. We report the case of a 52-year-old woman whose renal biopsy, done for glomerular proteinuria, shows membranous nephropathy with monotypic IgG4 deposits with no overt hematologic malignancy and no anti-PLA2R antibodies.


3D morphometrics of craniofacial dysmorphology reveals sex-specific asymmetries in schizophrenia.
Over early fetal life cerebral and craniofacial morphogenesis proceed in embryological intimacy. Therefore, craniofacial shape differences between schizophrenia patients and controls are informative of developmental disturbance(s) in cerebral-craniofacial morphogenesis. 3D craniofacial coordinates were calculated from interlandmark distances for 169 patients with DSM-III-R schizophrenia and 78 matched normal controls. These were analysed using geometric morphometrics with visualisation of the resultant statistical models. Patients of both sexes were characterised by an intricate topography of 3D shape change involving lengthened lower mid-facial height, shortened upper mid-facial height, nasion located posteriorly and a wider face posteriorly; there was sex-specific rotation of the midface such that the base of the nose is more anterior in female patients but more posterior in male patients. Importantly, there were sex-specific asymmetries: in males, controls evidenced marked directional asymmetry while patients showed reduced directional asymmetry; conversely, in females controls evidenced little directional asymmetry while patients showed marked directional asymmetry. In schizophrenia, the topography of craniofacial dysmorphology appears to reflect subtle disruption to a critical 3D trajectory of embryonic-fetal craniofacial growth, particularly along the midline, with disturbance to the establishment of normal asymmetries in a sex-related manner.


Atrovirisidone B, a new prenylated depsidone with cytotoxic property from the roots of Garcinia atroviridis.
A new prenylated depsidone, atrovirisidone B (2), together with naringenin (3) and 3,8"-binaringenin (4) were isolated from the roots of Garcinia atroviridis. Their structures were determined on the basis of spectral data interpretation. Compound 2 showed cytotoxic activity against human breast (MCF-7), human prostate (DU-145) and human lung (H-460) cancer cells.


Analysis of 6-mercaptopurine in human plasma with a high-performance liquid chromatographic method including post-column derivatization and fluorimetric detection.
A relatively simple assay with improved reliability and sensitivity for measuring levels of 6-mercaptopurine in human plasma is presented. After extraction of the compound and the added internal standard with phenyl mercury acetate, samples were separated by ion-pair reversed-phase high-performance liquid chromatography. On-line the analytes were oxidized to fluorescent products and detected in a flow-fluorimeter. The within-day coefficient of variation was 3.8% at a concentration of 25 ng/ml. The lower detection limit was 2 ng/ml when 1.0 ml of plasma was used. Mercaptopurine concentration versus time curves of two subjects after a single oral dose of azathioprine are shown.


[The Difficult Airway with Tracheostomy - Manufacturing of an Individualized Tracheal Tube with Modern Imaging and 3D Printing].
Case discussion of a 51-year-old female patient with ventilator dependency due to Charcot-Marie-Tooth-Hoffmann syndrome (HMSN I) and cervical spinal fusion with complex tracheal canula management. Following 16 years of noninvasive ventilation due to chronic hypercapnic failure with 24 hour dependency on the ventilator, an elective surgical tracheostomy and switch to invasive ventilation was carried out. Because of severe cervical scoliosis, common tracheal canulae could not provide an adequate fit. With development of a 3D model according to the CT scans of the patient, an individualized tracheal tube was customized that provided excellent ventilatory results and the ability to speak during invasive ventilation.


A randomised controlled trial of bag-valve-mask teaching techniques.
Bag-valve-mask (BVM) ventilation is a vital skill in the management of the collapsed patient; however, the quality of BVM ventilation is a cause for concern. Modified techniques, designed to be easier for the novice practitioner, offer an opportunity to improve quality. One such modification is the 'LASOO' (Lift, Apply, Slide, Oppose, Observe) approach, which offers theoretical benefits over the traditionally taught 'CE' (finger shapes) technique. We conducted a randomised controlled trial (RCT) to determine whether LASOO was superior to CE in terms of tidal volume, when taught to novices in the skills-lab setting. We conducted a randomised controlled trial (RCT) to determine whether LASOO was superior to CE in terms of tidal volume, when taught to novices in the skills-lab setting METHODS: A total of 76 undergraduate health care students received a manikin-based teaching session on LASOO or CE. They then delivered 20 breaths (10 with each hand) to a modified airway manikin. The primary outcome was mean tidal volume; secondary outcomes were the proportion of breaths that achieved 150-mL and 400-mL threshold volumes. Subgroup analyses and statistical modelling were conducted for time-point, hand dominance and hand size. The mean tidal volume was 320 mL for CE and 304 mL for LASOO. The median percentage of attempts that exceeded 150 mL was 85 for CE and 82.5 for LASOO. The median percentage of attempts that exceeded 400 mL was 20 for CE and 20 for LASOO. The differences recorded between the techniques were not statistically significant. There was a small, statistically significant increase in tidal volume across both techniques with time-point and holding the mask with the non-dominant hand. LASOO is a viable alternative to CE. Educators may opt to teach either or both techniques, allowing students to choose the technique that they prefer.


Human small intestinal epithelial cells constitutively express the key elements for antigen processing and the production of exosomes.
In humans, the small intestinal epithelial cells (IEC) have a high constitutive expression of MHC class II (MHC II), and contains lysosomes. The IEC also contains MHC II rich multivesicular compartments and has been shown to produce exosomes. This suggests a role for the IEC in antigen processing and presentation either directly or indirectly by the production of exosomes. However, the presence and localisation in the IEC of other key molecules involved in this process has not been studied previously. In the present work, we have investigated small intestinal biopsies from healthy adults and the HT29 IEC cell line with monoclonal antibodies against molecules involved in the antigen processing/presenting systems and molecules typically found on exosomes derived from professional APCs and IECs. Immunohistology was performed to study the expression and localisation of MHC II (HLA-DR), HLA-DM, MHC I (HLA-ABC), CD1d, Invariant chain, Lamp-1, CD68, CD63, B7.1, B7.2, ICAM-1, Cathepsin D/S/L and the IEC specific marker A33 in the IECs. We found that the IECs from the biopsies constitutively express MHC II, HLA-DM, MHC I, Invariant chain, Lamp-1, CD 68, CD63 and A33, and these markers were also found in the IFN-g treated HT-29 cells. All these molecules were found apically in the IECs of the biopsies, localised mainly in vesicular structures. Interestingly, in the baso-latereral area of the IEC, only MHC II, MHC I, Lamp 1, CD68, CD63 and A33 were found and also here with vesicular staining pattern which matches the molecules previously found on exosomes derived professional APCs and human IEC lines. CD1d, B7, ICAM-1, CD9 and cathepsin D and L were absent in the IEC compartment, but cathepsin S showed a relatively weak staining in the apical part of the IEC. The staining pattern and the morphological localisation of these markers suggest a prominent antigen processing/loading and trafficking compartment, and a possible baso-lateral release of exosomes in the normal human IEC.


Systemic Intake of Proton Pump Inhibitors and Selective Serotonin Reuptake Inhibitors May Be Associated With Implant Failure.
Medication-related dental implant failure: Systematic review and meta-analysis. Chappuis V, Avila-Ortiz G, Araújo MG, Monje A. Clin Oral Implants Res 2018;29 Suppl 16:55-68. None. The authors declared no conflict of interest. Systematic review with meta-analysis.


Placement of integrated self-expanding Y-shaped airway stent in management of carinal stenosis.
To investigate the feasibility and effectiveness of integrated self-expanding Y-shaped airway stent placement for patients with carinal stenosis. From May 2010 to March 2015, 12 consecutive patients with carinal stenosis, treated by placement of integrated self-expanding Y-shaped airway stent, were included this retrospective study. Data on technical success, clinical success, and follow-up were analyzed. Technical success was 100 %. Eleven uncovered stents and one covered stent placed in 12 patients. Eleven patients underwent stent insertion under local pharyngeal anesthesia, and one patient underwent stent insertion under general anesthesia. Clinical success was 100 %. The respiratory difficulty improved instantly after treatment. The average Hugh-Jones classification grade and arterial oxygen saturation improved from 4.3 ± 0.6 and 83.0 ± 2.6 % before treatment to 1.4 ± 0.5 (p < 0.001) and 95.4 ± 1.2 % (p < 0.001) after treatment, respectively. During 3-15 months (mean 6.5 ± 3.3 months) of follow-up, two patients experienced the re-stenosis of the stent 75 and 78 days after treatment. All patients died during the follow-up. Survival after stent insertion ranged from 96 to 432 days (median 165 days). The cumulative 6- and 12-month survival rates were 41.7 and 8.3 %, respectively. Placement of integrated self-expanding Y-shaped airway stent is a simple, safe, and effective method for patients with carinal stenosis.


Postoperative pain management in obstetric anesthesia--new challenges and solutions.
The current understanding of pain processing mechanisms, the different pharmacologic drugs, and other nonpharmacologic means that can be used to manage postobstetric operation pain are reviewed.


Myocardial protection during open-heart surgery: intermittent aortic crossclamping versus coronary perfusion.
Twenty-seven patients undergoing open-heart surgery were divided into three groups, i.e., control, intermittent aortic crossclamping and coronary perfusion groups. Myocardial oxygen extraction, lactate extraction, arterial-coronary sinus hydrogen ion difference, potassium difference and glucose difference were determined during the operation, as well as, postoperative stroke and cardiac indices and comparisons were made. When the ascending aorta was not crossclamped, myocardial metabolism was well preserved during and after the perfusion at a flow rate of 2.0 L./min/m2. Intermittent aortic crossclamping for 15 minutes alternating with a period of perfusion for five minutes at 30 degrees C was sufficient to protect the myocardium from ischemia. Perfusion of the left coronary artery alone at a flow rate of six per cent of total body perfusion (150 to 200 ml per minute) at 30 degrees C was sufficient to protect the myocardium when the aorta was opened. Since intermittent perfusion of the left coronary artery may produce myocardial derangement, coronary perfusion should be continuous. Otherwise topical cardiac cooling or other means of myocardial protection should be used.


Decisions under risk in Parkinson's disease: preserved evaluation of probability and magnitude.
Unmedicated Parkinson's disease patients tend to be risk-averse while dopaminergic treatment causes a tendency to take risks. While dopamine agonists may result in clinically apparent impulse control disorders, treatment with levodopa also causes shift in behaviour associated with an enhanced response to rewards. Two important determinants in decision-making are how subjects perceive the magnitude and probability of outcomes. Our objective was to determine if patients with Parkinson's disease on or off levodopa showed differences in their perception of value when making decisions under risk. The Vancouver Gambling task presents subjects with a choice between one prospect with larger outcome and a second with higher probability. Eighteen age-matched controls and eighteen patients with Parkinson's disease before and after levodopa were tested. In the Gain Phase subjects chose between one prospect with higher probability and another with larger reward to maximize their gains. In the Loss Phase, subjects played to minimize their losses. Patients with Parkinson's disease, on or off levodopa, were similar to controls when evaluating gains. However, in the Loss Phase before levodopa, they were more likely to avoid the prospect with lower probability but larger loss, as indicated by the steeper slope of their group psychometric function (t(24) = 2.21, p = 0.04). Modelling with prospect theory suggested that this was attributable to a 28% overestimation of the magnitude of loss, rather than an altered perception of its probability. While pre-medicated patients with Parkinson's disease show risk-aversion for large losses, patients on levodopa have normal perception of magnitude and probability for both loss and gain. The finding of accurate and normally biased decisions under risk in medicated patients with PD is important because it indicates that, if there is indeed anomalous risk-seeking behaviour in such a cohort, it may derive from abnormalities in components of decision making that are separate from evaluations of size and probability.


Determination of 2,4-Dichlorophenoxyacetic acid in food and water samples using a modified graphene oxide sorbent and high-performance liquid chromatography.
In the present work, dispersive micro-solid phase extraction (D-μ-SPE) method using magnetic graphene oxide tert-butylamine (GO/Fe3O4/TBA) nanocomposite, as an efficient sorbent, was applied for determining 2,4-dichlorophenoxyacetic acid (2,4-D) in water and food samples. Detection was carried out using high-performance liquid chromatography (HPLC) instrument. Influential parameters of D-μ-SPE such as sorbent and its amount, elution solvent and its volume, adsorption and desorption times and pH of sample solution were investigated and optimized. Under the optimized conditions, limit of detection and quantitation values were 0.007 and 0.02 μg/mL, respectively. Recovery data for several real samples were obtained within the range of 88.0-94.0% with a relative standard deviation (RSD) less than 7.5%. The proposed method was successfully applied to quantitative determination of 2,4-D in several vegetables and water samples.


Timely disclosure of progress in long-term cancer survival: the boomerang method substantially improved estimates in a comparative study.
Monitoring cancer survival is a key task of cancer registries, but timely disclosure of progress in long-term survival remains a challenge. We introduce and evaluate a novel method, denoted "boomerang method," for deriving more up-to-date estimates of long-term survival. We applied three established methods (cohort, complete, and period analysis) and the boomerang method to derive up-to-date 10-year relative survival of patients diagnosed with common solid cancers and hematological malignancies in the United States. Using the Surveillance, Epidemiology and End Results 9 database, we compared the most up-to-date age-specific estimates that might have been obtained with the database including patients diagnosed up to 2001 with 10-year survival later observed for patients diagnosed in 1997-2001. For cancers with little or no increase in survival over time, the various estimates of 10-year relative survival potentially available by the end of 2001 were generally rather similar. For malignancies with strongly increasing survival over time, including breast and prostate cancer and all hematological malignancies, the boomerang method provided estimates that were closest to later observed 10-year relative survival in 23 of the 34 groups assessed. The boomerang method can substantially improve up-to-dateness of long-term cancer survival estimates in times of ongoing improvement in prognosis.


Risk factors for depression, anxiety, and PTSD symptoms in perinatal women during the COVID-19 Pandemic.
Pregnant women and women who recently gave birth are vulnerable to COVID-19-related psychosocial stresses. We assessed COVID-19-related health worries and grief, and current mental health symptoms (depression, generalized anxiety, and PTSD) in 1,123 U.S. women during the COVID-19 pandemic (May 21 to August 17, 2020) through a cross-sectional study design. Among our respondents, 36.4% reported clinically significant levels of depression, 22.7% for generalized anxiety, and 10.3% for PTSD. Women with pre-existing mental health diagnoses based on their self-reported history were 1.6-to-3.7 more likely to score at clinically significant levels of depression, generalized anxiety, and PTSD. Approximately 18% reported high levels of COVID-19-related health worries and were 2.6-to-4.2 times more likely to score above the clinical threshold for mental health symptoms. Approximately 9% reported high levels of grief and were 4.8-to-5.5 times more likely to score above the clinical threshold for mental health symptoms. Perinatal women with pre-existing mental health diagnoses show elevated symptoms during the COVID-19 pandemic. Although causation cannot be inferred, COVID-19-related health worries and grief experiences may increase the likelihood of mental health symptoms among those without pre-existing mental health concerns. Providers should develop strategies for addressing health-related worry and grief within their practice.


Continuous deep sea salt layer along North Atlantic margins related to early phase of rifting.
Deep seismic reflexion surveys have revealed diapiric structures in deep water off Labrador, Newfoundland, Mauritania, Morocco, Portugal, Spain and Ireland as well as in the Mediterranean. Many of these diapirs are similar to the Gulf of Mexico salt domes, and it is suggested that there is a continuous deep sea salt layer, off the continental margin, which is related to the early phase of rifting.


Use of optical flow to estimate continuous changes in muscle thickness from ultrasound image sequences.
Muscle thickness is one of the most widely used parameters for quantifying muscle function. Ultrasonography is frequently used to estimate changes in muscle thickness in both static and dynamic contractions. Conventionally, most such measurements are conducted by manual analysis of ultrasound images. This manual approach is time consuming, subjective, susceptible to error and not suitable for measuring dynamic change. In this study, we developed an automated tracking method based on an optical flow algorithm using an affine motion model. The goal of the study was to evaluate the performance of the proposed method by comparing it with the manual approach and by determining its repeatability. Real-time B-mode ultrasound was used to examine the rectus femoris during voluntary contraction. The coefficient of multiple correlation (CMC) was used to quantify the level of agreement between the two methods and the repeatability of the proposed method. The two methods were also compared by linear regression and Bland-Altman analysis. The findings indicated that the results obtained using the proposed method were in good agreement with those obtained using the manual approach (CMC = 0.97 ± 0.02, difference = -0.06 ± 0.22 mm) and were highly repeatable (CMC = 0.91 ± 0.07). In conclusion, the automated method proposed here provides an accurate, highly repeatable and efficient approach to the estimation of muscle thickness during muscle contraction.


Influence of cadmium on antioxidant capacity and four microelement concentrations in tomato seedlings (Lycopersicon esculentum).
Tomato (Lycopersicon esculentum) seedlings were grown in four cadmium (Cd) levels of 0-10 microM in a hydroponic system to analyze the antioxidative enzymes, Cd concentration in the plants, and the interaction between Cd and four microelements. The results showed that there was a significant increase in malondialdehyde (MDA) concentration, and superoxide dismutase (SOD) and peroxidase (POD) activities in the plants subjected to 1-10 microM Cd. This indicates that Cd stress induces an oxidative stress response in tomato plants, characterized by an accumulation of MDA and increase in activities of SOD and POD. Root, stem and leaf Cd concentrations increased with its exposure Cd level, and the highest Cd concentration occurred in roots, followed by leaves and stems. A concentration- and tissue-dependent response was found in the four microelement concentrations to Cd stress in the tomato leaves, stems and roots. Regression analysis showed that there was a significantly negative correlation between Cd and Mn, implying the antagonistic effect of Cd on Mn absorption and translocation. The correlation between Cd and Zn, Cu and Fe were inconsistent among leaves, stems and roots.


MRI of lumbar trunk muscles in patients with Parkinson's disease and camptocormia.
Camptocormia in Parkinson's disease (PD) is an axial postural disorder usually accompanied by histopathological changes in the paravertebral muscles of unknown etiology. The diagnostic potential of magnetic resonance imaging (MRI) of back muscles in camptocormia has not been systematically assessed. Our objective was to characterize pathological muscle changes with MRI and to develop radiological criteria for camptocormia. The criteria edema, swelling and fatty degeneration in 20 idiopathic PD patients with camptocormia were assessed using MRI (T1w and short tau inversion recovery (STIR) sequences) of the lumbar trunk muscles and compared with 20 group-matched PD patients without camptocormia. Edema and fatty degeneration of the paravertebral muscles were significantly more frequent in camptocormia. Edema correlated negatively and fatty degeneration positively with the duration of camptocormia and not PD. Swelling of the paravertebral muscles, edema and swelling of the quadratus lumborum muscle and rare edema of the psoas muscle were only found in camptocormia patients. In this case-control study the defined MRI criteria distinguish the group of PD patients with camptocormia versus those without. Our findings suggest dynamic changes in the MRI signals over time in the paravertebral muscles: edema and swelling are found initially, followed by fatty atrophic degeneration 2-3 years after the beginning of camptocormia. Muscle MRI qualifies as a tool for categorizing phases of camptocormia as acute or chronic, with potential consequences for therapeutic approaches. The involvement of muscles beyond an isolated impairment of the paravertebral muscles implies a more systemic view with a deregulation of lumbar trunk muscles.