Fluorescence and image guided resection in high grade glioma.
The extent of resection in high grade glioma is increasingly been shown to positively effect survival. Nevertheless, heterogeneity and migratory behavior of glioma cells make gross total resection very challenging. Several techniques were used in order to improve the detection of residual tumor. Aim of this study was to analyze advantages and limitations of fluorescence and image guided resection. A multicentric prospective study was designed to evaluate the accuracy of each method. Furthermore, the role of 5-aminolevulinc acid and neuronavigation were reviewed. Twenty-three patients harboring suspected high grade glioma, amenable to complete resection, were enrolled. Fluorescence and image guides were used to perform surgery. Multiple samples were obtained from the resection cavity of each lesion according to 5-ALA staining positivity and boundaries as delineated by neuronavigation. All samples were analyzed by a pathologist blinded to the intra-operative labeling. Decision-making based on fluorescence showed a sensitivity of 91.1% and a specificity of 89.4% (p<0.001). On the other hand, the image-guided resection accuracy was low (sensitivity: 57.8%; specificity: 57.4%; p=0.346). We observed that the sensitivity of 5-ALA can be improved by the combined use of neuronavigation, but this leads to a significant reduction in specificity. Thus, the use of auxiliary techniques should always be subject to critical skills of the surgeon. We advocate a large-scale study to further improve the assessment of multimodal approaches.


What's Luck Got to Do with It: Single Cells, Multiple Fates, and Biological Nondeterminism.
The field of single-cell biology has morphed from a philosophical digression at its inception, to a playground for quantitative biologists, to a major area of biomedical research. The last several years have witnessed an explosion of new technologies, allowing us to apply even more of the modern molecular biology toolkit to single cells. Conceptual progress, however, has been comparatively slow. Here, we provide a framework for classifying both the origins of the differences between individual cells and the consequences of those differences. We discuss how the concept of "random" differences is context dependent, and propose that rigorous definitions of inputs and outputs may bring clarity to the discussion. We also categorize ways in which probabilistic behavior may influence cellular function, highlighting studies that point to exciting future directions in the field.


Luteotrophic and luteolytic effects of nitric oxide in sheep are dose-dependent in vivo.
It has been suggested that nitric oxide (NO) acts in either an anti-luteolytic or in a luteolytic manner, but the mechanism for these opposing roles is unclear. We hypothesized that NO may act in a dose-dependent manner to regulate luteal function, whereby low concentrations of NO might stimulate luteal progesterone production (i.e. luteotrophic) and high concentrations of NO might reduce concentrations of plasma progesterone (i.e. luteolytic). To test this hypothesis we infused increasing concentrations of the fast-acting NO donor, dipropylenetriamine NONOate (DPTA), into the arterial supply of sheep with ovarian transplants bearing a corpus luteum (CL). Infusions were performed on sheep with CL 11 days of age (n=9) or over 30 days of age (n=15). We measured changes in the concentration of progesterone in ovarian venous plasma during the 1-h infusion and for 24h after the infusion, and then compared the mean concentration of progesterone between treatment groups for effects by dose and dose by period interactions. Compared with saline-treated controls (n=6), the highest dose of 1000 microg/min DPTA (n=6) reduced (P<or=0.05) the mean concentration of progesterone after the infusion. In sheep bearing a CL over 30 days of age, the 10 microg/min DPTA dose (n=3) markedly increased (P<or=0.05) the mean concentration of progesterone both during and after the infusion, whereas the 100 microg/min DPTA dose (n=3) increased (P<or=0.05) the mean concentration of progesterone only during the 1-h infusion. The mean concentration of progesterone was not different (P>0.05) in sheep infused with the lowest dose of 1 microg/min DPTA (n=6) compared with controls. We conclude that NO regulates luteal function in a dose-dependent manner in sheep in vivo.


Changes in the acoustic startle response and prepulse inhibition of acoustic startle in rats after local injection of pertussis toxin into the ventral tegmental area.
The effect of local injection of pertussis toxin (PTX) into the ventral tegmental area (VTA) on acoustic startle in rats was investigated. The PTX treatment caused only minor effects of its own on the acoustic startle response (ASR) or prepulse inhibition (PPI) of acoustic startle. However, systemic treatment with the indirect DA receptor agonist, amphetamine (2 mg/kg, SC) caused a significant increase in ASR magnitude and a significant disruption of PPI in PTX-treated rats while no such effects were observed in sham-treated rats. Treatment with the direct DA receptor agonist, apomorphine (2 mg/kg, SC), caused a significant disruption of PPI, an effect that was observed in both PTX- and sham-treated rats. Treatment with the 5-HT1A receptor agonist, 8-OH-DPAT (0.5 mg/kg, SC), did not affect PPI in either group but caused a marked increase in ASR magnitude in sham-treated rats. Interestingly, this effect was blocked in PTX-treated rats. The present results suggest that local injection of PTX into the VTA causes an increased sensitivity to the behavioural effects of psychostimulants on acoustic startle and may also suggest that intact midbrain 5-HT1A receptors are essential for the effect of 5-HT1A agonists on acoustic startle.


Large bowel obstruction secondary to a cecal bascule with internal herniation through the foramen of Winslow: A case report.
Internal hernias are a rare phenomenon, and even rarer is a herniation through the foramen of Winslow. The clinical presentation of patients with an internal hernia is often vague and difficult to diagnose clinically. If internal hernias go undiagnosed and untreated, patients can develop bowel compromise leading to a high morbidity and potential mortality. Radiologic imaging is helpful in bringing the diagnosis to the forefront of the clinicians mind, but the diagnosis is often made intra-operatively. An eighty-one year old female presenting with a few months of vague abdominal symptoms who was found to have a cecal bascule internally herniating through the foramen of Winslow was treated successfully with surgical intervention. Internal hernias occur when there is a protrusion of a viscera through the peritoneum or mesentery and confined within the abdominal cavity. Internal hernias are classified according to location and vary from paraduodenal, transmesenteric, and pelvic to name a few. Hernias through the foramen of Winslow are a rare subset, and were the internal hernia found in our patient intra-operatively. Our patient's clinical presentation was vague with generic abdominal complaints and radiologic imaging was inconclusive for a definitive diagnosis. However, prompt surgical intervention resulted in a good outcome for our patient. Internal hernias, to be diagnosed and treated promptly, require a high index of suspicion from a clinician based on clinical presentation and radiologic imaging. These patients belong in the operating room, and interventions are directed based on the anatomical findings intra-operatively.


Gender differences in sleep patterns for early adolescents.
To describe gender differences in self-reported sleep disturbances and daytime sleepiness in an urban sample of early adolescents (11-14 years of age). One hundred and forty-four racially diverse sixth- to eighth-grade students responded to an investigator-developed sleep questionnaire. Variables included school night and weekend sleep patterns as well as factors that influence sleep and daytime sleepiness, such as sleep/wake routine and alcohol and caffeine consumption. Boys consumed significantly more caffeinated beverages than girls, but this did not correlate with self-reports of waking after sleep onset. Caffeine intake was significantly related to self-reported parasomnias. Significant gender differences were found for self-reports of daytime sleepiness. There were also large variations between weekday and weekend sleep schedules. Weekday wakeup time for boys was significantly later compared to girls. Those who reported consumption of alcohol during the past week were likely to fall asleep in the classroom before lunch. Girls, who awakened earlier than boys on school days, were more likely to report falling asleep on the way home from school. These descriptive data support the need for further investigation into the relationship between caffeine intake and parasomnias, as well as into the observed gender differences.


[Sports-related fractures of the facial skull in Austria].
Details of injuries to the maxillo-facial region have been collected over a five year period. 635 fractures in this region were registered resulting from 24 different sports. Soccer was found as the most dangerous individual sport. There is no absolute safe kind of sport but we suggest that the number of fractures depends too on a local factor.


In ovo vaccination technology.
More than 80% of the U.S. broiler industry has converted to the in ovo vaccination process for control of Marek's disease. Providing certain criteria are met, including timing and site of vaccine placement, vaccine mixing, machine sanitization, and hatchery management specifications, this has proven to be an efficacious and convenient method of vaccination. Efforts to extend the technology for other viral vaccines including Newcastle, bronchitis and bursal disease, and bacterial and parasitic vaccines are in progress. Collectively, these studies demonstrate that in ovo vaccination technology using approved vaccine is a safe, efficacious, and convenient method for vaccination of poultry.


Notching is less, if femoral component sagittal positioning is planned perpendicular to distal femur anterior cortex axis, in navigated TKA.
In navigated TKA, the risk of notching is high if femoral component sagittal positioning is planned perpendicular to the sagittal mechanical axis of femur (SMX). We intended to determine if, by opting to place the femoral component perpendicular to distal femur anterior cortex axis (DCX), notching can be reduced in navigated TKA. We studied 171 patients who underwent simultaneous bilateral computer-assisted TKA. Femoral component sagittal positioning was planned perpendicular to SMX in one knee (Femur Anterior Bowing Registration Disabled, i.e. FBRD group) and perpendicular to DCX in the opposite knee (Femur Anterior Bowing Registration Enabled, i.e. FBRE group). Incidence and depth of notching were recorded in both groups. For FBRE knees, distal anterior cortex angle (DCA), which is the angle between SMX and DCX, was calculated by the computer. Incidence and mean depth of notching was less (p = 0.0007 and 0.009) in FBRE versus FBRD group, i.e. 7% versus 19.9% and 0.98 mm versus 1.53 mm, respectively. Notching was very high (61.8%) in FBRD limbs when the anterior bowing was severe (DCA > 3°) in the contralateral (FBRE) limbs. Notching was less when femoral component sagittal positioning was planned perpendicular to DCX, in navigated TKA. Therapeutic level II.


Ethnopharmacology of Rubus idaeus Linnaeus: A critical review on ethnobotany, processing methods, phytochemicals, pharmacology and quality control.
Rubus idaeus Linnaeus (RI) is a Chinese herbal medicine that has been widely used in China for a long time to reinforce the kidney, nourish the liver, improve vision, and arrest polyuria. This work aims to evaluate the recent progress of the chemical composition, pharmacological activity, pharmacokinetics, metabolism, and quality control and of Rubus idaeus, which focuses on the insufficiency of existing research and will shed light on future studies of Rubus idaeus. Literatures about "Rubus idaeus","Red raspberry" and "Fupenzi"are retrieved by browsing the database, such as Web of Science (http://www.webofknowledge.com/wos), Pubmed (https://pubmed.ncbi.nlm.nih.gov/), CNKI (http://www.cnki.net/), and Wanfang Data (http://www.wanfangdata.com.cn). In addition, related textbooks and digital documents are interrogated to provide a holistic and critical review of the topic. The period of the literature covered from 1981 to 2022. Approximately 194 compounds have been isolated from Rubus idaeus, which is rich in phenols, terpenoids, alkaloids, steroids, and fatty acids. Numerous investigations have demonstrated that Rubus idaeus exhibits many pharmacological activities, including hypoglycemic and hypolipidemic, anti-Alzheimer effect, anti-osteoporosis, hepatoprotective, anti-cancer, neuroprotective, anti-bacteria and skin care, etc. However, it is worth noting that most of the research is not associated with the conventional effect, such as reducing urination and treating opacity of the cornea. The effectiveness of Rubus idaeus has been proved by its long-term clinical application. The research on the pharmacological activity of Rubus idaeus has flourished. In many pharmacological experiments, only the high-dose group can achieve the corresponding efficacy, so the efficacy of Rubus idaeus needs to be further interrogated. Meanwhile, the relationship between pharmacological activity and specific compounds of Rubus idaeus has not been clarified yet. Last but not least, studies involving toxicology and pharmacokinetics are very limited. Knowledge of bioavailability and toxicological behavior of Rubus idaeus can help understand the herb's pharmacodynamic and safety profile.


Improvement of the butyl methacrylate-paraffin embedment.
The excellent butyl methacrylate-paraffin method as an embedment for light microscopy has been technically improved. More uniform and reproducible polymerization has been obtained by using a vacuum oven to degas the polymerizing mixture and to replace the air with nitrogen at 650 Torr. The amount of benzoyl peroxide required must be determined for each batch of butyl methacrylate. A teflon lined, reusable metal mold and a method of one-step blocking of tissues in preparation for sectioning are also described.


Sustainability and Climate Protection in Radiology - An Overview.
Sustainability is becoming increasingly important in radiology. Besides climate protection - economic, ecological, and social aspects are integral elements of sustainability. An overview of the scientific background of the sustainability and environmental impact of radiology as well as possibilities for future concepts for more sustainable diagnostic and interventional radiology are presented below.The three elements of sustainability:1. EcologyWith an annually increasing number of tomographic images, Germany is in one of the leading positions worldwide in a per capita comparison. The energy consumption of an MRI system is comparable to 26 four-person households annually. CT and MRI together make a significant contribution to the overall energy consumption of a hospital. In particular, the energy consumption in the idle or inactive state is responsible for a relevant proportion.2. EconomyA critical assessment of the indications for radiological imaging is important not only because of radiation protection, but also in terms of sustainability and "value-based radiology". As part of the "Choosing Wisely" initiative, a total of 600 recommendations for avoiding unnecessary examinations were compiled from various medical societies, including specific indications in radiological diagnostics.3. Social SustainabilityThe alignment of radiology to the needs of patients and referring physicians is a core aspect of the social component of sustainability. Likewise, ensuring employee loyalty by supporting and maintaining motivation, well-being, and job satisfaction is an essential aspect of social sustainability. In addition, sustainable concepts are of relevance in teaching and research, such as the educational curriculum for residents in radiology, RADUCATION or the recommendations of the International Committee of Medical Journal Editors. · Sustainability comprises three pillars: economy, ecology and the social component.. · Radiologies have a high optimization potential due to a significant demand of these resources.. · A dialogue between medicine, politics and industry is necessary for a sustainable radiology.. · The discourse, knowledge transfer and public communication of recommendations are part of the sustainability network of the German Roentgen Society (DRG).. · Palm V, Heye T, Molwitz I et al. Sustainability and Climate Protection in Radiology - An Overview. Fortschr Röntgenstr 2023; 195: 981 - 988.


Severe cat flea infestation of dairy calves in Brazil.
An investigation was conducted into a severe flea infestation on dairy calves. Inspection of the dairy revealed a high infestation of Ctenocephalides felis felis on four calves and thousands of fleas in the stable where cows and calves were brought in for milking. A 3-month-old female calf was highly infested with fleas. The animal showed an evident lethargy, weight loss, as well as pale mucous membranes and dehydration. Hematological analysis revealed anemia, with 10% packed cell volume and a 1.72 x 10(6) microl(-1) erythrocyte count. Blood transfusions were performed and the flea infestation was controlled with 1% fipronil pour-on (1 ml/10 kg). The farmer was advised to treat the other calves with fipronil, remove the manure from the stable and spread 1% propoxur powder (100 g/m2) onto the floor of the stable.


Is treatment too late: what ten years of evaluative research tell us.
Since 1974, the U.S. federal government has funded four major multiyear evaluation studies to determine the relative effectiveness of different approaches to the treatment of child abuse and neglect. A total of 89 different demonstration treatment programs were studied, and data on 3,253 families experiencing difficulties with abuse and neglect were gathered. Collectively, the studies document treatment approaches which improve clients' functioning (notably lay counseling and various group services including Parents Anonymous, group therapy, and parent evaluation) and suggest greater success with clients experiencing difficulty with sexual abuse than other forms of maltreatment. However, overall the studies show that one-third or more of the parents served by these intensive demonstration efforts maltreated their children while in treatment, and over one-half of the families served continued to be judged likely to mistreat their children following termination.


Alpinetin inhibits breast cancer growth by ROS/NF-κB/HIF-1α axis.
Alpinetin, the main active ingredient in the Chinese medicinal herb Alpinia katsumadai Hayata, has been found to have anticancer activity. However, the therapeutic efficacy of signalling cascades modulated by alpinetin remains unknown. Here, we showed that alpinetin provoked mitochondria-associated apoptosis in a dose-dependent manner in breast cancer cells. Mechanistic investigations revealed that alpinetin dampens hypoxia-inducible factor-1α (HIF-1α) signalling due to a lack of NF-κB activation through reduced mitochondrial reactive oxygen species (ROS) production, decreasing HIF-1α transcription. In vivo, we also found alpinetin led to significant tumour regression by inhibiting NF-κB pathway. Overall, our work uncovers a ROS/NF-κB/HIF-1α axis-dependent mechanism underlying the anticancer effects of alpinetin and suggests that alpinetin could act as a novel therapeutic agent against breast cancer.


Gallbladder carcinoma.
Although it is the most common cancer of the biliary tree, gallbladder carcinoma remains an uncommon disease. As a result, many clinicians rarely encounter it and there is uncertainty regarding proper management. Resection is the most effective and only potentially curative treatment. Early stage tumors are often curable with a proper resection; however, many patients present late in the course of the disease when surgical intervention is no longer effective. While other treatment modalities are used in patients with advanced disease, there is limited data on efficacy. In many cases, the diagnosis is made after a cholecystectomy has been performed and an incidental tumor is identified in the specimen. In such cases, reoperation and definitive resection is appropriate and effective for patients with invasive lesions.


Effect of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) with Hydroxyapatite Carrier in Induced Membrane Technique: A Retrospective Propensity Score-Matched Study.
To determine the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) with hydroxyapatite (HA) carrier augmentation in managing critical-sized bone defect (CSBD) with induced membrane technique (IMT). Retrospective comparative study. Academic level I trauma center. The study included 14 patients who underwent rhBMP-2 with HA carrier (rhBMP-2/HA) augmentation in IMT for managing CSBD (BMP group). Moreover, 14 patients who underwent IMT without rhBMP-2 augmentation were matched by propensity score analysis (non-BMP group). IMT with or without rhBMP-2/HA augmentation. Changes in quality and quantity measurements of grafted bone to regenerated bone using serial computed tomography. In the BMP and non-BMP groups, the changes in densities from grafted bone to regenerated bone were +379.63 Hounsfield unit and +248.55 Hounsfield unit (P = 0.034), changes in dense bone percentage were +37.52% and +23.31% (P = 0.027), corticalization rates under the plate were 79.70% and 39.30% (P = 0.007), changes in volume were -20.77% and -23.35% (P = 0.812), union rates were 85.71% and 78.57% (P = 0.622), numbers of patients requiring additional procedures were 4 and 3 (P = 0.663), and time to union were 316.3 and 585.45 days (P = 0.040), respectively. RhBMP-2/HA augmentation increases the density of regenerated bone, enhances corticalization under the plate, and shortens the time to union while managing CSBD with IMT. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Antihyperalgesic activity of the methanol extract and some constituents obtained from Polygala cyparissias (Polygalaceae).
Polygala cyparissias, used in folk medicine as an anaesthetic, has already demonstrated antinociceptive activity against acute pain. In this study, we investigated the antihyperalgesic activity of the P. cyparissias methanol extract (PCME) from which the following compounds were isolated: α-spinasterol (PC1), 1,3-dihydroxy-7-methoxyxanthone (PC2), 1,7-dihydroxy-2,3-methylenedioxyxanthone (PC3) and 1,3,6,8-tetrahydroxy-2,7-dimethoxyxanthone (PC4). The antihyperalgesic effect was evaluated using experimental models of persistent pain induced by carrageenan, lipopolysaccharide (LPS), Freund's Complete Adjuvant (CFA), PGE(2) or epinephrine. The partial ligation of the sciatic nerve (PLSN) model was also used. In inflammatory hyperalgesia induced by carrageenan, LPS, CFA or PGE(2), the inhibition values obtained with the PCME treatment were 68 ± 3%, 89 ± 5%, 43 ± 3% and 40 ± 4%, respectively. In epinephrine-induced hyperalgesia, the extract was effective, reducing 99 ± 11% of response frequency, while in PLSN, 54 ± 4% of inhibition was obtained. These results allow to suggest that the antihyperalgesic activity of PCME is, at least in part, related to its capability to inhibit the hypersensitization induced by pro-inflammatory mediators, such as LPS, carrageenan and CFA, without interfering with locomotor activity or motor performance. Furthermore, compounds PC1, PC3 and PC4 inhibited the carrageenan-induced hyperalgesia with inhibition of 42 ± 6%, 48 ± 5% and 64 ± 4%, respectively. In summary, our data demonstrate that PCME has relevant antihyperalgesic activity and that the isolated PC1, PC3 and PC4 seem to be responsible, at least in part, for this important effect.


Spinal alignment in low back pain patients and age-related side effects: a multivariate cross-sectional analysis of video rasterstereography back shape reconstruction data.
Spinal form in the sagittal plane and asymmetries of spinal alignment in the frontal plane were identified earlier to be associated with low back pain. This study was aiming at investigating whether age was influencing the significance of these findings. Spinal alignment of 155 older and 58 younger low back pain patients was investigated using non-invasive video rasterstereography and compared to 192 pain free controls. Trunk inclination and imbalance, pelvis tilt and torsion, and the thoracic kyphosis and lumbar lordosis angle served as dependent variables, which were analyzed using multivariate procedures. Frontal plane parameters-trunk imbalance (λ > 0.60) in combination with pelvis tilt (λ > 0.64)-constituted an independent component in a factor analysis model of spine shape parameters in younger and older patients, but not in pain free controls. Trunk imbalance (frontal), trunk inclination (sagittal) and partially thoracic kyphosis angle (sagittal) were extracted to separate patients from controls (discriminant coefficients >0.50). Age could not be excluded as interfering variable for the lumbar lordosis angle. Significant univariate analyses revealed higher effect sizes for trunk imbalance and inclination (η (2) > 0.07) than for lordosis, kyphosis or pelvic parameters (η (2) < 0.06). In line with corresponding findings trunk imbalance remained a low back pain-associated parameter not depending on age. Over all, sagittal trunk inclination and the thoracic kyphosis angle could not be established as being completely free from age influences, while the lumbar lordosis angle played a minor role and seemed to be influenced more by age than by low back pain in this rasterstereography study.


Immunomodulatory properties of MSC-derived exosomes armed with high affinity aptamer toward mylein as a platform for reducing multiple sclerosis clinical score.
Mesenchymal stem cell-derived exosome is a safe and effective delivery platform with a potential capacity to exert immunomodulation effect and peripheral tolerance toward auto-reactive cells via bearing regulatory and tolerogenic molecules. Inflammation and neurodegeneration are the clinical manifestation of multiple sclerosis (MS). In order to fight against MS, the efficient choices are the ones, which prevent inflammation and induce remyelination. In this regard, the previously reported LJM-3064 aptamer which showed considerable affinity toward myelin and demonstrated remyelination induction was employed as both targeting ligand and therapeutic agent. Thus, in the current study, the carboxylic acid-functionalized LJM-3064 aptamer was covalently conjugated to the amine groups on the exosome surface through EDC/NHS chemistry. The obtained results showed that the aptamer-exosome bioconjugate could promote the proliferation of oligodendroglia cell line (OLN93) in vitro. Moreover, in vivo administration of the prepared aptamer-exosome bioconjugate in female C57BL/6 mice as a prophylactic measure produced a robust suppression of inflammatory response as well as lowered demyelination lesion region in CNS, resulting in reduced in vivo severity of the disease. The prepared platform employing exosome-based nanomedicine as a novel approach for managing MS would hopefully pave the way to introduce a versatile approach toward an effective clinical reality.


Evaluation of Mitochondrial Function in the CNS of Rodent Models of Alzheimer's Disease - High Resolution Respirometry Applied to Acute Hippocampal Slices.
Alzheimer's disease (AD) is a multifactorial disease characterized by extracellular deposits of amyloid plaques and intracellular neurofibrillary tangles. These hallmark alterations are preceded by synaptic deterioration, changes in neuromolecular plasticity phenomena, mitochondrial dysfunction, increase in oxidative damage to cellular constituents and decreased energy metabolism. The hippocampus is a structure of the temporal medial lobe implicated in specific forms of memory processes. It is also one of the first and most affected regions of the CNS in AD. Here we present a novel approach to the study if mitochondrial function/disfunction in 2 rodent models of AD: an acute rat model obtained by intracerebroventricular injection of the toxin streptozotocin (STZ) and a progressive triple transgenic mouse model (3TgAD) harboring PS1M146V, APPSwe, and tauP301L transgenes. Mitochondrial dysfunction has classically been assessed in such models by isolating mitochondria, synaptossoms or working with cell cultures. Anyone of these approaches destroys the intricate intercellular connectivity and cytoarchitecture of neuronal tissue. We used acute hippocampal slices obtained from the 2 models of AD and evaluated changes in mitochondrial function as a function of disease and/or age. Mitochondrial stress test were performed on the high resolution respirometry (Oroboros 2K Oxymeter). Upon analysis of oxygen consumption rates (OCR) we observed significant decreases in basal OCR, maximal respiratory capacity, ATP turnover and a tendency for decrease in sparing capacity in the STZ rat model compared to shame injected animals. Regarding the 3TgAD model we observed an age-dependent decrease in all parameters evaluated in the mitochondrial stress test, in both 3TgAD and NTg animals. However, although a tendency towards decreased OCR was observed when comparing 3TgAD and age-matched NTg animals, no statistically significant difference was observed.


Intermediate filaments in Merkel cell tumors.
A series of ten Merkel cell tumors is described, with special emphasis on intermediate filament expression. The presence of cytoskeletal proteins was studied with a polyclonal antiserum directed against cytokeratin and with monoclonal antibodies against cytokeratin, neurofilament, and vimentin by the immunoperoxidase technique. Cytokeratin was demonstrated in nine of ten tumors. Neurofilament was observed in the two snap-frozen tissues tested and in three of the eight formalin-fixed, paraffin-embedded tissues. No reactivity for vimentin was found. By electron microscopy desmosomes were found to be present in all cases, while tonofilaments were found in only a few cases. neurosecretory granules, although seen in all tumors, were generally present in low numbers. The results of this study indicate that the Merkel cell tumor is a poorly differentiated small cell carcinoma that has the ability to express some neuroendocrine features.


Association of Undernutrition and Early Childhood Dental Caries.
To determine the association between early childhood caries and nutritional status in preschool children. Cross-sectional study among preschool children (N=550, age 8-60 mo) were selected in tribal, rural and urban health care units of Kerala. An oral examination for early childhood caries status was done using Deft index. The anthropometric measurements were recorded. Multiple logistic regression with other covariates was used to determine the association between the early childhood caries and nutritional status. The mean (SD) Deft scores were 0.93 (1.73), 2.22 (2.92) and 3.40 (3.23) for children with normal nutritional status, borderline undernutrition and undernutrition, respectively. Children with borderline undernutrition (adjusted OR 2.05, 95% CI 1.20, 3.49) or undernutrition (adjusted OR 3.46, 95% CI 1.93, 6.29) had higher odds of dental caries in comparison to those with normal nutritional status. Undernutrition is associated with early childhood caries among preschool children.


Sternalis is muscle: An anatomic variation and its clinical implications.
This report presents a case description of sternalis muscle which is an accessory muscle of anterior thoracic wall. A 56-year-old woman underwent mastectomy for breast cancer along with free flap reconstruction, revealing the presence of aberrant sternalis muscle. It was divided transversely during partial rib resection to expose internal mammary vessels. The case proceeded with successful flap transfer. Clinical implications of this anatomic variation is discussed. The authors conclude that plastic surgeons should be aware of this muscular anomaly.


SurgGrip: a compliant 3D printed gripper for vision-based grasping of surgical thin instruments.
This paper presents a conceptual design and implementation of a soft, compliant 3D printed gripper (SurgGrip), conceived for automated grasping of various surgery-based thin-flat instruments. The proposed solution includes (1) a gripper with a resilient mechanism to increase safety and better adaptation to the unstructured environment; (2) flat fingertips with mortise and tenon joint to facilitate pinching and enveloping based grasping of thin and random shape tools; (3) a soft pad on the fingertips to enable the high surface area to maintain stable grasping of the surgical instruments; (4) a four-bar linkage with a leadscrew mechanism to provide a precise finger movement; (5) enable automated manipulation of surgical tools using computer vision. Our gripper model is designed and fabricated by integrating soft and rigid components through a hybrid approach. The SurgGrip shows passive adaptation through inherent compliance of linear and torsional spring. The four-bar linkage mechanism controlled by a motor-leadscrew-nut drive provides precise gripper opening and closing movements. The experimental results show that the SurgGrip can detect, segment through a camera, and grasp surgical instruments (maximum 606.73 gs), with a 67% success rate (grasped 10 out of 12 selected tools) at 3.21 mm/s grasping speed and 15.81 s object grasping time autonomously. Besides, we demonstrated the pick and place abilities of SurgGrip on flat and nonflat surfaces in real-time. The online version contains supplementary material available at 10.1007/s11012-022-01594-6.


[To the controversy of the priority about the conservation of mother's milk in the german-speaking territory (author's transl)].
The differing opinions of Prof. Dr. med. E. Mayerhofer (Vienna-Zagreb) and Dr. M.-E. Kayser (Magdeburg-Erfurt) on the conservation of mother's milk and the characteristics of a mother's milk bank are discussed and the relevant achievements of the two physicians are evaluated.


Obesity Modifies the Performance of Fibrosis Biomarkers in Nonalcoholic Fatty Liver Disease.
Guidelines recommend blood-based fibrosis biomarkers to identify advanced nonalcoholic fatty liver disease (NAFLD), which is particularly prevalent in patients with obesity. To study whether the degree of obesity affects the performance of liver fibrosis biomarkers in NAFLD. Cross-sectional cohort study comparing simple fibrosis scores [Fibrosis-4 Index (FIB-4); NAFLD Fibrosis Score (NFS); aspartate aminotransferase to platelet ratio index; BARD (body mass index, aspartate-to-alanine aminotransferase ratio, diabetes); Hepamet Fibrosis Score (HFS)] and newer scores incorporating neo-epitope biomarkers PRO-C3 (ADAPT, FIBC3) or cytokeratin 18 (MACK-3). Tertiary referral center. We recruited overweight/obese patients from endocrinology (n = 307) and hepatology (n = 71) clinics undergoing a liver biopsy [median body mass index (BMI) 40.3 (interquartile range 36.0-44.7) kg/m2]. Additionally, we studied 859 less obese patients with biopsy-proven NAFLD to derive BMI-adjusted cutoffs for NFS. Biomarker area under the receiver operating characteristic (AUROC), sensitivity, specificity, and predictive values to identify histological stage ≥F3 fibrosis or nonalcoholic steatohepatitis with ≥F2 fibrosis [fibrotic nonalcoholic steatohepatitis (NASH)]. The scores with an AUROC ≥0.85 to identify ≥F3 fibrosis were ADAPT, FIB-4, FIBC3, and HFS. For fibrotic NASH, the best predictors were MACK-3 and ADAPT. The specificities of NFS, BARD, and FIBC3 deteriorated as a function of BMI. We derived and validated new cutoffs for NFS to rule in/out ≥F3 fibrosis in groups with BMIs <30.0, 30.0 to 39.9, and ≥40.0 kg/m2. This optimized its performance at all levels of BMI. Sequentially combining FIB-4 with ADAPT or FIBC3 increased specificity to diagnose ≥F3 fibrosis. In obese patients, the best-performing fibrosis biomarkers are ADAPT and the inexpensive FIB-4, which are unaffected by BMI. The widely used NFS loses specificity in obese individuals, which may be corrected with BMI-adjusted cutoffs.


[The prepyloric Finsterer-Operation; technique and results (author's transl)].
Between 1963 and 1971 47 Patients with not resectable duodenal ulcer who underwent this type of operation were followed up. The complication rate was low, the long term results were good.


Cyclodextrin as a magic switch in covalent and non-covalent anticancer drug release systems.
Cancer has been a threat to human health, so its treatment is a huge challenge to the present medical field. One of commonly used methods is the controlled release of anticancer drug to reduce the dose for patients, increase the stability of drug treatment and minimize side effects. Cyclodextrin is a kind of cyclic oligosaccharide produced by amylase hydrolysis. Because cyclodextrin contains a cavity structure and active hydroxyl groups, it has a positive effect on the study of the controlled release of anticancer drugs. This article reviews the controlled release of current anticancer drugs based on cyclodextrins as a "flexible switch", and discusses the classification of different types of release systems, highlighting their role in cancer treatment. Moreover, the opportunities and challenges of cyclodextrin as a magic switch in the controlled release of anticancer drugs are discussed.


Molecular biology of somatostatin receptors.
The neuropeptide somatostatin (SRIF) has diverse physiological actions in the brain and endocrine organs. A family of SRIF receptors has recently been cloned that may mediate the distinct biological effects of SRIF. These receptors have a high degree of amino acid sequence similarity among themselves, but their sequences are different from any other receptors, indicating that they represent a distinct neurotransmitter receptor subfamily. The availability of the cloned receptors will now allow for detailed structure-function analysis of SRIF receptors and will facilitate development of subtype-selective agonists and antagonists that could be useful in the treatment of central nervous system and endocrine disorders.


[Maximal androgen blockade in the treatment of patients with disseminated cancer of the prostate].
Up-to-date approaches to treatment of disseminated prostatic cancer are discussed, including the experience of the use of maximum androgen blockade in 120 patients. The procedure may be recommended to start hormonal therapy in such patients with.


Genetic diversity of culturable bacteria in oil-contaminated rhizosphere of Galega orientalis.
A collection of 50 indigenous meta-toluate tolerating bacteria isolated from oil-contaminated rhizosphere of Galega orientalis on selective medium was characterized and identified by classical and molecular methods. 16S rDNA partial sequencing showed the presence of five major lineages of the Bacteria domain. Gram-positive Rhodococcus, Bacillus and Arthrobacter and gram-negative Pseudomonas were the most abundant genera. Only one-fifth of the strains that tolerated m-toluate also degraded m-toluate. The inoculum Pseudomonas putida PaW85 was not found in the rhizosphere samples. The ability to degrade m-toluate by the TOL plasmid was detected only in species of the genus Pseudomonas. However, a few Rhodococcus erythropolis strains were found which were able to degrade m-toluate. A new finding was that Pseudomonas migulae strains and a few P. oryzihabitans strains were able to grow on m-toluate and most likely contained the TOL plasmid. Because strain specific differences in degradation abilities were found for P. oryzihabitans, separation at the strain level was important. For strain specific separation (GTG)5 fingerprinting was the best method. A combination of the single locus ribotyping and the whole genomic fingerprinting techniques with the selective partial sequencing formed a practical molecular toolbox for studying genetic diversity of culturable bacteria in oil-contaminated rhizosphere.


Resting-state EEG and MEG biomarkers of pathological fatigue - A transdiagnostic systematic review.
Fatigue is a highly prevalent and disabling symptom of many disorders and syndromes, resulting from different pathomechanisms. However, whether and how different mechanisms converge and result in similar symptomatology is only partially understood, and transdiagnostic biomarkers that could further the diagnosis and treatment of fatigue are lacking. We, therefore, performed a transdiagnostic systematic review (PROSPERO: CRD42022330113) of quantitative resting-state electroencephalography (EEG) and magnetoencephalography (MEG) studies in adult patients suffering from pathological fatigue in different disorders. Studies investigating fatigue in healthy participants were excluded. The risk of bias was assessed using a modified Newcastle-Ottawa Scale. Semi-quantitative data synthesis was conducted using modified albatross plots. After searching MEDLINE, Web of Science Core Collection, and EMBASE, 26 studies were included. Cross-sectional studies revealed increased brain activity at theta frequencies and decreased activity at alpha frequencies as potential diagnostic biomarkers. However, the risk of bias was high in many studies and domains. Together, this transdiagnostic systematic review synthesizes evidence on how resting-state M/EEG might serve as a diagnostic biomarker of pathological fatigue. Beyond, this review might help to guide future M/EEG studies on the development of fatigue biomarkers.


(±)-Heterocageflavone, anti-inflammatory isoprenylated flavonoids with a tricyclo[5.3.1.03,8]undecane moiety from Artocarpus heterophyllus.
(±)-Heterocageflavone (1), a pair of enantiomeric isoprenylated flavonoids, were isolated from Artocarpus heterophyllus. Compound 1 incorporates an unusual tricyclo[5.3.1.03,8]undecane moiety, forming a unique caged polycyclic system. The structures of the pair were determined by spectroscopic analysis, ECD calculations, and single-crystal X-ray diffraction. Compound 1 showed significant inhibitory activity against LPS-induced NO production in RAW264.7 cells with an IC50 value of 49.2 μM.


Exiguobacterium mediated arsenic removal and its protective effect against arsenic induced toxicity and oxidative damage in freshwater fish, Channa striata.
Arsenic is a toxic metalloid existing widely in the environment, and its removal from contaminated water has become a global challenge. The use of bacteria in this regard finds a promising solution. In the present study, Exiguobacterium sp. As-9, which is an arsenic resistant bacterium, was selected with respect to its arsenic removal efficiency. Quantification of arsenic in the water treated with bacterium showed that Exiguobacterium efficiently removed up to 99% of arsenic in less than 20 h. In order to reveal the possible effect of this bacterium in removal of arsenic from water and protecting fishes from the detrimental effects of arsenic, we initiated a range of studies on fresh water fish, Channa striata. It was observed that the fishes introduced into bacteria treated water displayed no symptoms of arsenic toxicity which was marked by a decreased oxidative damage, whereas the fishes exposed to arsenic revealed a significant (p < 0.05) increase in the oxidative stress together with the elevated levels of malondialdehyde. Determination of the bioaccumulation of arsenic in the liver tissues of C. striata using hydride generation atomic absorption spectrophotometry (HG-AAS) revealed an increased As(III) accumulation in the fishes exposed to arsenic whereas the arsenic level in the control and bacteria treated fishes were found below the detectable limit. In conclusion, this study presents the strategies of bacterial arsenic removal with possible directions for future research.


Francisella-Like Endosymbiont Detected in Haemaphysalis Ticks (Acari: Ixodidae) From the Republic of Korea.
A total of 6,255 ticks belonging to three genera and six species (Haemaphysalis flava Neumann, Haemaphysalis longicornis Neumann, Haemaphysalis phasiana Saito, Ixodes nipponensis Kitaoka & Saito, Ixodes persulcatus Schulze, and Amblyomma testudinarium Koch) collected from May-August, 2013, at four southwestern provinces in the Republic of Korea (ROK) were submitted to the Armed Forces Research Institute of Medical Sciences and assayed for selected tick-borne pathogens. One pool each of H. flava and H. phasiana was positive by PCR and sequencing for a Francisella-like endosymbiont, while all pools were negative for Francisella tularensis, the causative agent of tularemia.


Fungicide Resistance of Alternaria alternata and A. arborescens Isolates from Mandarin Fruit and Its Influence on Control of Postharvest Alternaria Rot.
Alternaria rot, caused by Alternaria alternata and A. arborescens, is one of the common postharvest diseases affecting mandarin fruit in California. Fungicide resistance profilings of A. alternata and A. arborescens to quinone outside inhibitors (QoIs), fludioxonil, pyrimethanil, imazalil, and propiconazole were examined in this study. Of the 100 isolates of A. alternata and A. arborescens, 40 were identified as resistant to QoI fungicides according to a PCR-restriction fragment length polymorphism based on a cytochrome b partial gene. Effective concentrations of fludioxonil that caused a 50% reduction in fungal growth relative to the control (EC50) were 0.089 ± 0.020 and 0.101 ± 0.032 µg/ml for 43 A. alternata and 19 A. arborescens isolates, respectively. EC50 values of pyrimethanil, imazalil, and propiconazole for the 70 A. alternata isolates tested were 0.373 ± 0.161, 0.492 ± 0.133, and 1.135 ± 0.407 µg/ml, respectively. EC50 values of pyrimethanil, imazalil, and propiconazole for 30 A. arborescens isolates were 0.428 ± 0.190, 0.327 ± 0.180, and 0.669 ± 0.452 µg/ml, respectively. Control tests on mandarin fruit inoculated with representative isolates of both species showed that fludioxonil, pyrimethanil, imazalil and propiconazole significantly reduced disease incidence and severity. Azoxystrobin significantly reduced Alternaria rot severity and incidence on mandarin fruit inoculated with sensitive isolates but not with resistant isolates, regardless of Alternaria spp. There were no significant differences in Alternaria rot control effectiveness if treatment with any of the fungicides tested was delayed after inoculation by 6 or 12 h. These results could help in the development of postharvest fungicide programs to control Alternaria rot on mandarin fruit during storage.


On H-antimagic coverings for m-shadow and closed m-shadow of connected graphs.
An ( a , d ) -H-antimagic total labeling of a simple graph G admitting an H-covering is a bijection φ : V ( G ) ∪ E ( G ) → { 1 , 2 , … , | V ( G ) | + | E ( G ) | } such that for all subgraphs H ' of G isomorphic to H, the set of H ' -weights given by w t φ ( H ' ) = ∑ v ∈ V ( H ' ) φ ( v ) + ∑ e ∈ E ( H ' ) φ ( e ) forms an arithmetic sequence a , a + d , … , a + ( t - 1 ) d where a > 0 , d ⩾ 0 are two fixed integers and t is the number of all subgraphs of G isomorphic to H. Moreover, such a labeling φ is called super if the smallest possible labels appear on the vertices. A (super) ( a , d ) -H-antimagic graph is a graph that admits a (super) ( a , d ) -H-antimagic total labeling. In this paper the existence of super ( a , d ) -H-antimagic total labelings for the m-shadow and the closed m-shadow of a connected G for several values of d is proved.


Effect of leukocyte hydrolases on bacteria. XIII. Role played by leukocyte extracts, lysolecithin, phospholipase a2, lysozyme, cationic proteins, and detergents in the solubilization of lipids from Staphylococcus aureus and group A streptococci: relation to bactericidal and bacteriolytic reactions in inflammatory sites.
The bactericidal and bacteriolytic effects of lysolecithin (LL) and egg-white lysozyme (LYZ) on Staph. aureus and group A streptococci and the solubilization of phospholipids from the bacterial membranes by these agents was studied. Low concentrations of lysolecithin (1--10 microgrames/ml) are highly bactericidal for Steph. aureus and group A streptococci, but induce neither bacteriolysis nor solubilization of a substantial amount of membrane phospholipids. On the other hand, while LL at greater than 50 micrograms/ml causes substantial lipid release, a combination of LL and LYZ is absolutely needed to solubilize lipids from streptococci. This combination is, however, not bacteriolytic for this microrganism. The solubilization of lipids from staphylococci by LL is much faster than that induced in streptococci by LL + LYZ. The solubilization of the bulk of membrane lipids from staphylococci can also be achieved by Triton X-100 and by sodium lauryl sulfate and from group A streptococci by Triton X-100 plus LYZ. A variety of other detergents (e.g., Cetavlon, sodium taurocholate, cetyl pyrdinium chloride) have no lipid-releasing properties even in the presence of LYZ. The release of lipids by LYZ (in the presence of LL) from group A streptococci is related to its enzymatic activity, on a still unknown substrate, but not to its cationic nature as this muramidase cannot be replaced by a variety of cation substances (histone, polylysin, leukocyte cationic proteins, polymyxin B, and spermidine). The release of lipids from staphylococci by LL is not inhibited by a variety of anionic and cationic polyelectrocytes (heparin, liquoid, chondroitin sulfate, DNA histone, and polylysine) which markedly inhibit the release of lipids from group A streptococci by LL and LYZ. Streptococci that had been cultivated in the presence of subinhibitory concentrations of penicillin G lose their membrane phospholipids to a larger extent and by much smaller concentrations of LL and LYZ, as compared to controls, suggesting that the interference with the synthesis of the peptidoglycan increases the accessibility of the cell membrane to the lipid-releasing agents. The mechanism by which LL collaborates with LYZ in lipid release is still not known. The possible role of bacterial lipids and lyso compounds in the control of bacterial survival in inflammatory sites is briefly discussed.


New once-daily formulation for trospium in overactive bladder.
AIMS We examined the relative efficacy and safety of trospium 20 mg bid and 60 mg extended release formulations and position this drug against other antimuscarinic agents. Data were identified on the pharmacology and pharmacokinetics of trospium chloride. Key publications on trospium 20-mg and 60-mg clinical studies in patients with overactive bladder (OAB) were identified and efficacy and safety compared between these formulations as well as other antimuscarinic agents. Trospium offers the principal advantage over other antimuscarinic agents that, as it is a quaternary amine, it does not cross the blood-brain barrier and is therefore less likely to cause central nervous system effects observed with several other agents. Moreover, with its minimal liver metabolisation, independent of the main cytochrome pathways, trospium has a low risk of drug-drug interaction in patients taking multiple pharmacological agents. Trospium 60 mg ER is as effective as trospium 20 mg bid in improving the key outcome parameters associated with OAB, but with a lower rate of dry mouth, the most common side effect of these agents. Trospium has comparable efficacy and safety to the other antimuscarinic agents currently marketed. Good patient persistence with treatment has been reported with trospium. There are currently a large number of antimuscarinic drugs on the market without clear evidence to distinguish one agent from another in terms of efficacy, provided that an adequate dose is used in the clinical setting. The new formulation of trospium is certainly worth considering as a pharmacological treatment of patients with OAB, particularly in the elderly, in whom one wants to avoid the potential for cognitive dysfunction.


The effect of emergency department pharmacists on drug overuse and drug underuse in patients with an ADE-related hospitalisation: a controlled intervention study.
Drug overuse or drug underuse are the most common causes of adverse drug events and can lead to hospital admissions. Using clinical pharmacists in the emergency department may improve patient safety as they are specialised in recognising of adverse drug events and tackling drug overuse and drug underuse. This study tested the effect of an emergency department pharmacist on the number of medication changes for drug overuse and drug underuse taking place in patients with an adverse drug event-related hospitalisation following an emergency department visit. A multicenter prospective non-randomized controlled intervention study was conducted in a university hospital and a general teaching hospital. Trained emergency department pharmacists included patients in the intervention group with a hospital admission related to an adverse drug event. The interdisciplinary intervention consisted of a pharmacist-led medication review, patient counselling regarding medication, and information transmission to general practitioners and community pharmacies after discharge. The control patients were also admitted after an emergency department visit and received the usual care. The primary outcome was the number of medication changes for drug overuse and drug underuse that took place during hospital admission and persisted 6 months thereafter. Poisson regression analysis was used to estimate the difference in these medication changes between the intervention group and the control group. A total of 216 patients were included (intervention group 104, control group 112). In the intervention group, 156 medication changes for drug overuse and drug underuse persisted 6 months after admission compared to 59 in the control group (adjusted rate ratio 1.22 [95%CI 1.01-1.49] p = 0.039). Emergency department pharmacists do contribute to reduction of drug overuse and drug underuse of medication in patients with a hospitalisation related to adverse drug events after an emergency department visit.


Photothermal treatment of glioblastoma cells based on plasmonic nanoparticles.
Photothermal therapy based on plasmonic gold nanoparticles is considered a promising approach for cancer treatment. Here, we investigate the in vitro photothermal effect of 30-nm gold nanoparticles, optically excited with a 532-nm continuous laser, on the U87MG malignant glioblastoma cells, and demonstrate the role of nanoparticle concentration and exposure power density in achieving its optimum performance. Laser-induced collective oscillation of electrons in plasmonic gold nanoparticles is employed to generate localized heat to denature tumor cells. Optical spectroscopy is used to measure the plasmonic band of nanoparticles and select the excitation laser light. The MTT assay for the IC50 viability assessment is performed to evaluate the live and metabolically active cells after treatment with plasmonic nanoparticles. The quantitative data is statistically analyzed using analysis of variance followed by Tukey's post hoc test. The viability test demonstrates that the metabolic activity of treated U87MG was decreased compared with untreated cells, leading to the determination of the IC50 as 92 [Formula: see text]. A 532-nm laser light was selected for the excitation of gold nanoparticles since the maximum plasmonic band is at 524 nm. The viability tests show that although cells have natural photothermal agents, their absorption efficiency is very low; therefore, the laser-induced plasmonic effect is necessary to observe photothermal effects. The optimal condition was achieved when the nanoparticle concentration was 92 [Formula: see text], and the exposure power density was 96 [Formula: see text]. Thus, it is demonstrated that plasmonic nanoparticle concentration and laser exposure power density are among the key parameters in the photothermal treatment of cancer cells, and higher concentrations of Au-NPs and laser power density lead to less cell viability in the selected range due to the excitation of gold nanoparticles' localized surface plasmon resonance.


[Osteogenesis imperfecta].
The paper describes patients with osteogenesis imperfecta (oi). It gives the causes of oi, shows types according to Sillence. Discuss clinical and radiological appearance of the patients. It provides the latest information about rehabilitation and surgical treatment (multilevel osteotomies and rodding), and supplementation of osteoporosis connecting with oi.


Nurses' and preschool teachers' experiences of taking part in a participatory intervention project in communication-intense working environments.
Noise is a common workplace problem that can affect health and performance. High sound levels have been found in sectors that largely has been overlooked in noise research such as health care and education. In these communication-intense environments the work requires speech communication, thus making it difficult to wear hearing protection. To explore nurses' and preschool teachers' experiences of taking part in a participatory intervention project aiming to improve the sound environment and the psychosocial work environment. One preschool and one obstetrics ward took part in the study, and a qualitative design was used to evaluate the experience of the participatory intervention approach. Five main themes were found in the analysis: Awareness; Taking control of the sound environment; Influence of the building and interior design; Circumstances influencing the intervention process; and Motivation to maintain change. Despite demanding working situations and lack of financial resources, preschool and obstetrics staff described being creative in planning and implementing several different solutions to improve the sound environment at their workplaces, while interventions specifically improving the psychosocial work environment were fewer. Hence, our study suggest that a participatory intervention approach may facilitate participation and motivation, but resources and support are needed for a comprehensive and effective implementation.


Structural characterization of oligosaccharides in recombinant soluble human interferon receptor 2 using fluorophore-assisted carbohydrate electrophoresis.
The N-linked oligosaccharide profiles (banding patterns in gels) and structures of recombinant soluble human interferon receptor 2 (r-shIFNAR2) were determined using fluorophore-assisted carbohydrate electrophoresis (FACE, Glyko, Novato, CA). The method involves releasing N-linked oligosaccharide moieties from a glycoprotein by digestion with peptide-N glycanase (PNGase F), labeling the released oligosaccharides with the fluorescent dye 8-aminonaphthalene-1,3,6-trisulfonate (ANTS), and separating the labeled oligosaccharides by gel electrophoresis. The isolated oligosaccharides in the bands from the profiling gels can then be sequenced using exoglycosidases to reveal the oligosaccharide structures. The oligosaccharide profile of r-shIFNAR2 consists of at least nine oligosaccharide bands. The relative amount of oligosaccharide in each band can vary, depending on the culture conditions of the source cells. FACE structural analysis shows that r-shIFNAR2 contains only core-fucosylated N-linked oligosaccharides, most of which are fully sialylated (approximately 92%). The major types and relative amounts of the oligosaccharides from a representative sample are: disialylated, galactosylated, biantennary (15%); trisialylated, galactosylated, triantennary (19%), tetrasialylated, galactosylated, tetraantennary (30%), and N-acetyllactosamine-containing higher-order oligosaccharides including tri-, tetra-, and pentaantennary (28%). The remaining oligosaccharides are not fully sialylated and/or not fully galactosylated di-, tri-, and tetraantennary structures (approximately 5%) and unidentified structures (approximately 3%). A method for determining the types and structures of the N-acetyllactosamine containing oligosaccharides is also reported in this study.


Insertional translocation into the X chromosome of a 46,XY male.
A baby boy with multiple congenital anomalies and low birth weight has an apparent de novo insertional translocation into the long arm of his only X chromosome. The origin of the translocated material is not evident and both cytogenetic and X-linked marker studies do not indicate any loss of genetic material from the X chromosome. His findings are compared with other males who have X-translocations, none of which appear to be insertional translocations.


Frequent horizontal and mother-to-child transmission may contribute to high prevalence of STLV-1 infection in Japanese macaques.
Simian T-cell leukemia virus type 1 (STLV-1) is disseminated among various non-human primate species and is closely related to human T-cell leukemia virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Notably, the prevalence of STLV-1 infection in Japanese macaques (JMs) is estimated to be > 60%, much greater than that in other non-human primates; however, the mechanism and mode of STLV-1 transmission remain unknown. The aim of this study is to examine the epidemiological background by which STLV-1 infection is highly prevalent in JMs. The prevalence of STLV-1 in the JMs rearing in our free-range facility reached up to 64% (180/280 JMs) with variation from 55 to 77% among five independent troops. Anti-STLV-1 antibody titers (ABTs) and STLV-1 proviral loads (PVLs) were normally distributed with mean values of 4076 and 0.62%, respectively, which were mostly comparable to those of HTLV-1-infected humans. Our initial hypothesis that some of the macaques might contribute to frequent horizontal STLV-1 transmission as viral super-spreaders was unlikely because of the absence of the macaques exhibiting abnormally high PVLs but poor ABTs. Rather, ABTs and PVLs were statistically correlated (p < 0.0001), indicating that the increasing PVLs led to the greater humoral immune response. Further analyses demonstrated that the STLV-1 prevalence as determined by detection of the proviral DNA was dramatically increased with age; 11%, 31%, and 58% at 0, 1, and 2 years of age, respectively, which was generally consistent with the result of seroprevalence and suggested the frequent incidence of mother-to-child transmission. Moreover, our longitudinal follow-up study indicated that 24 of 28 seronegative JMs during the periods from 2011 to 2012 converted to seropositive (86%) 4 years later; among them, the seroconversion rates of sexually matured (4 years of age and older) macaques and immature macaques (3 years of age and younger) at the beginning of study were comparably high (80% and 89%, respectively), suggesting the frequent incidence of horizontal transmission. Together with the fact that almost all of the full-adult JMs older than 9 years old were infected with STLV-1, our results of this study demonstrated for the first time that frequent horizontal and mother-to-child transmission may contribute to high prevalence of STLV-1 infection in JMs.


Clinical aspects in the surgical treatment of varicocele in subfertile men. II. The role of the epididymal factor.
Ninety-six couples, consulting for primary (n = 73) or secondary (n = 23) infertility, and thought to be infertile due to a varicocele in the husband associated with sperm abnormalities, were subjected to a follow-up study. Of these, 57 were surgically corrected and 39 were not, depending only on the patient's choice. All women were intensively treated where necessary. All patients who were corrected were subjected to scrotal exploration in a search for epididymal anomalies. From our data we conclude that (1) on a statistical basis, comparing observed with expected pregnancy rates, varicocelectomy is useful in primary infertility and unnecessary in secondary infertility and (2) on an individual basis, patients with primary infertility and 'pure' varicoceles have a better prognosis than patients with concomitant epididymal dysfunction.


Cutting Edge: Unconventional CD8+ T Cell Recognition of a Naturally Occurring HLA-A*02:01-Restricted 20mer Epitope.
Unconventional HLA class I-restricted CD8+ T cell epitopes, longer than 10 aa, have been implicated to play a role in human immunity against viruses and cancer. T cell recognition of long peptides, centrally bulging from the HLA cleft, has been described previously. Alternatively, long peptides can contain a linear HLA-bound core peptide, with a N- or C-terminal peptide "tail" extending from the HLA peptide binding groove. The role of such a peptide "tail" in CD8+ T cell recognition remains unclear. In this study, we identified a 20mer peptide (FLPTPEELGLLGPPRPQVLA [FLP]) derived from the IL-27R subunit α gene restricted to HLA-A*02:01, for which we solved the crystal structure and demonstrated a long C-terminal "tail" extension. FLP-specific T cell clones demonstrated various recognition modes, some T cells recognized the FLP core peptide, while for other T cells the peptide tail was essential for recognition. These results demonstrate a crucial role for a C-terminal peptide tail in immunogenicity.


Wooded Semi-Natural Habitats Complement Permanent Grasslands in Supporting Wild Bee Diversity in Agricultural Landscapes.
Loss of semi-natural habitats (SNH) in agricultural landscapes affects wild bees, often negatively. However, how bee communities respond varies and is still unclear. To date, few studies have used precise descriptors to understand these effects. Our aim was to understand the respective and complementary influences of different wooded and herbaceous habitats on wild bee communities. We selected thirty 500-m radius landscapes on a gradient of a percentage of wooded SNH in south-western France. At each landscape, we sampled wild bees in spring 2016 and plants in spring 2015 and 2016 at the forest edge, in a hedgerow, and in a permanent grassland. Pollen carried by the most abundant bee species was collected and identified. Using beta diversity indices, we showed that wild bee community composition differs between the three SNH types, and especially between herbaceous and wooded SNH. Based on Jacobs' selection index, we showed that pollen of some plant species recorded in wooded SNH are preferentially selected by wild bees. Studying the impact of the loss of each SNH type on the global bee-pollen interaction network, we found that wooded SNH contributed to its resilience, enabling specific plant-bee interactions. Overall, our results underline the non-negligible contribution of wooded SNH to the diversity of wild bees in agricultural landscapes, and thus the importance of maintaining different types of SNH.


Localized increases in corticotropin-releasing factor receptors in pulp after dental injury.
Corticotropin-releasing factor (CRF) binds to membrane-bound CRF receptors (CRF-Rs). Among the actions mediated by activated CRF-Rs is beta-endorphin (END) release from immune cells, increasing peripheral antinociception. For assessment of inflammatory regulation of CRF-R expression, rats underwent pulp exposure of left, first mandibular molars and recovered for 6 days. Control pulpal tissue consisted of contralateral, uninjured molars and left, first mandibular molars of uninjured animals. Pulp tissue specimens were incubated with antibodies directed against CRF-R (both isoforms), neurofilament, CD45, and END. We observed (1) increases in pulp CRF-R immunoreactivity after injury, (2) increased CRF-R immunoreactivity expressed in 3 distinct zones in relation to the injury, and (3) increased CD45 and END immunoreactivity in regions surrounding the pulpal abscess. CRF-Rs might provide an additional target for novel analgesics to treat pulpal pain.


The 6pi, phosphide-stabilised stannylene dianion [C6H4P2Sn]2-; the first member of a new class of Arduengo-type carbene analogues.
Dilithiation of 1,2-(PH2)2C6H4 with nBuLi followed by reaction with Sn(NMe2)2 in the presence of the Lewis base donor tmeda [Me2NCH2CH2NMe2] gives [(C6H4P2Sn)(Li.tmeda)2] , containing the phosphide-stabilised, 6pi stannylene dianion [C6H4P2Sn]2-.


Bioalkylation of nucleic acids in mice by insecticides. I. Alkylation of liver RNA and DNA by chlorpyrifos.
Male mice were i.p. injected with two doses (5 & 15 mg/kg body weight) of [1-14C]ethyl-labelled chlorpyrifos. The radioactivity in liver, fat, kidney and urine was measured 6, 24, 48, and 192 h after treatment. Liver RNA and DNA were isolated and hydrolyzed and the bases separated by ion-exchange chromatography. Radioactivity resulting from incorporation and alkylation of RNA and DNA was measured. Labelled 7-ethylguanine was found in RNA hydrolysate which amounted 5.5 X 10(-3) calculated as fraction of the applied dose. In DNA hydrolysate [14C]7-ethylguanine was missing and the major radioactivity was found in two unknown peaks, one of which corresponds to 3 X 10(-2) of the applied dose. The results indicate that the extent of alkylation obtained with chlorpyrifos is high as compared with other organophosphates with methyl esters.


High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis.
An active stroma is important for cancer cell invasion and metastasis. We investigated the expression of fibroblast activation protein (FAP) in relation to patient prognosis in colorectal cancer. Colorectal cancer specimens from 449 patients were immunohistochemically stained with a FAP antibody and evaluated in the tumor center and tumor front using a semiquantitative four-level scale. FAP was expressed by fibroblasts in 85-90 % of the tumors examined. High versus no/low expression in the tumor center was associated with poor prognosis (multivariate hazard ratio, HR = 1.72; 95 % CI 1.07-2.77, p = 0.025). FAP expression in the tumor front, though more frequent than in the tumor center, was not associated with prognosis. FAP expression in the tumor center was more common in specimens with positive microsatellite instability (MSI) screening status and in patients with high CpG island methylator phenotype (CIMP) status. However, inclusion of MSI screening status and CIMP status in the multivariate analysis strengthened the risk estimates for high FAP expression in the tumor center (HR = 1.89; 95 % CI 1.13-3.14; p = 0.014), emphasizing the role of FAP as an independent prognostic factor. Stromal FAP expression is common in colorectal cancer, and we conclude that high FAP expression in the tumor center, but not the tumor front, is an independent negative prognostic factor.


Mask-related costs in measuring preview benefit: Evidence from a distributional analysis based on target word reading times.
Skilled reading involves processing the upcoming word in parafoveal vision before it is fixated, leading to shorter fixations on that word. This phenomenon, parafoveal preview benefit, is a key component of theoretical models of reading; it is measured using the invisible boundary paradigm, in which reading times on a target word are compared for instances when preview is accurate and when the target word is masked while in the parafovea. However, parafoveal masks have been shown to induce unintentional processing costs, thereby inflating measures of preview benefit. The degraded mask has been explored as a potential solution to this problem, leading to mixed results. While previous work has analyzed the preview effect by comparing mean reading times on the target word, the present study provides a more comprehensive analysis by examining the distribution of the preview effect across target word fixation times for unrelated and degraded masks. Participants read sentences containing target words whose preview was either identical, unrelated, or degraded, and their eye movements were recorded. Analyses revealed that although there were no mean differences between reading times for the unrelated and degraded conditions, the pattern of the effects varied as a function of target word fixation times. Unrelated masks resulted in positively sloped generally linear delta plots, while degraded masks resulted in relatively flat delta plots for fixations longer than 200 ms. These differences suggest that different cognitive mechanisms are involved in the processing of the two mask types. Implications for understanding and measuring preview benefit are discussed.


Untapped Neuroimaging Tools for Neuro-Oncology: Connectomics and Spatial Transcriptomics.
Neuro-oncology research is broad and includes several branches, one of which is neuroimaging. Magnetic resonance imaging (MRI) is instrumental for the diagnosis and treatment monitoring of patients with brain tumors. Most commonly, structural and perfusion MRI sequences are acquired to characterize tumors and understand their behaviors. Thanks to technological advances, structural brain MRI can now be transformed into a so-called average brain accounting for individual morphological differences, which enables retrospective group analysis. These normative analyses are uncommonly used in neuro-oncology research. Once the data have been normalized, voxel-wise analyses and spatial mapping can be performed. Additionally, investigations of underlying connectomics can be performed using functional and structural templates. Additionally, a recently available template of spatial transcriptomics has enabled the assessment of associated gene expression. The few published normative analyses have shown relationships between tumor characteristics and spatial localization, as well as insights into the circuitry associated with epileptogenic tumors and depression after cingulate tumor resection. The wide breadth of possibilities with normative analyses remain largely unexplored, specifically in terms of connectomics and imaging transcriptomics. We provide a framework for performing normative analyses in oncology while also highlighting their limitations. Normative analyses are an opportunity to address neuro-oncology questions from a different perspective.


Fate of silver nanoparticles in constructed wetlands and its influence on performance and microbiome in the ecosystems after a 450-day exposure.
Great controversy still exists on the ecological effects of silver nanoparticles (AgNPs) especially at relatively low concentrations. The performance, fate of AgNPs and microbiome in CWs were evaluated under a long-term exposure to AgNPs (0, 50 and 200 µg/L) for 450 days. Results showed that AgNPs (50, 200 µg/L) caused no obviously negative effects on COD removal whereas nitrogen and phosphorus removals were slightly stimulated. AgNPs could be removed efficiently from wastewater attributed to the accumulations of soil and plant tissues. Mass balance of AgNPs was analysed and soil layer of CWs was the major sink of nanoparticles. High-throughput sequencing further revealed the impact of AgNPs on the ecological structure of CWs. Moreover, the presence of AgNPs altered the relative abundances of key functional bacteria. The ecological risks of persistent exposure to low concentrations AgNPs should not be ignored, even though it did not result in deterioration of the CWs' operating performance in our studies.


The complexity of the serine glycine one-carbon pathway in cancer.
The serine glycine and one-carbon pathway (SGOCP) is a crucially important metabolic network for tumorigenesis, of unanticipated complexity, and with implications in the clinic. Solving how this network is regulated is key to understanding the underlying mechanisms of tumor heterogeneity and therapy resistance. Here, we review its role in cancer by focusing on key enzymes with tumor-promoting functions and important products of the SGOCP that are of physiological relevance for tumorigenesis. We discuss the regulatory mechanisms that coordinate the metabolic flux through the SGOCP and their deregulation, as well as how the actions of this metabolic network affect other cells in the tumor microenvironment, including endothelial and immune cells.


Development of insulated isothermal PCR for rapid on-site malaria detection.
Detection of Plasmodium spp. is sometimes inconvenient especially in rural areas that are distant from a laboratory. In this study a portable diagnostic test of Plasmodium spp. was developed using insulated isothermal polymerase chain reaction (iiPCR) as an alternative approach to improve this situation. A pair of universal primers and probe were designed to amplify and detect gene encoding 18S small sub-unit rRNA of Plasmodium spp using iiPCR method in a portable device, POCKIT™. The efficiency and detection limit of the assay were evaluated using quantitative real-time polymerase chain reaction (qPCR) approach before being subjected to testing in POCKIT™. Detection results of POCKIT™ were displayed as '+', '-' or '?' based on the fluorescence ratio after/before reaction. A total of 55 and 35 samples from malaria patients and healthy subjects, respectively, were screened to evaluate the feasibility of this newly designed iiPCR assay. The iiPCR assay allowed the detection of various species of Plasmodium, including those infecting humans (Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae, P. ovale), monkeys, birds, and rodents. Efficiency of the assay achieved 96.9 % while the lower detection limit was ≥100 copies of plasmodial DNA. Specificity of the assay was assured as it could not detect human, bacterial and other parasitic DNA. Among the 55 clinical samples tested, 47 (85.4 %) of them were detected as positive by POCKIT™. Four (7.3 %) samples with fluorescence ratio after/before reaction of <1.2 were reported as negative while another four (7.3 %) were ambiguously detected as they had fluorescence ratios between 1.2 and 1.3. The fluorescence ratio was not found to be associated with the copy number of plasmodial DNA. This approach can only be considered as a qualitative method. The portable iiPCR system may serve as an alternative approach for preliminary screening of malaria in endemic rural areas. The system may also be useful for detecting animal malaria in the field. Although it is not as quantitative as qPCR method, it is comparatively fast and easy to handle. It is believed that the POCKIT-iiPCR assay is able to achieve 100 % sensitivity if increased amount of DNA from each sample is used. The iiPCR assay can also be upgraded in future to detect multiple Plasmodium spp. at the same time by designing the specific primers and probes.


Enough is enough: feedback control of specialized metabolism.
Recent advances in our understanding of plant metabolism have highlighted the significance of specialized metabolites in the regulation of gene expression associated with biosynthetic networks. This opinion article focuses on the molecular mechanisms of small-molecule-mediated feedback regulation at the transcriptional level and its potential modes of action, including metabolite signal perception, the nature of the sensor, and the signaling transduction mechanisms leading to transcriptional and post-transcriptional regulation, based on evidence available from plants and other kingdoms of life. We also discuss the challenges associated with identifying the occurrences, effects, and localization of small molecule-protein interactions. Further understanding of small-molecule-controlled metabolic fluxes will enable rational design of transcriptional regulation systems in metabolic engineering to produce high-value specialized metabolites.


The use of adhesively retained gold onlays in the management of dental erosion in a child: a 4-year case report.
Tooth erosion, particularly in young people, presents a considerable challenge to restorative dentistry. A case of a 12-year-old is described where the use of minimal tooth preparation, precious metal onlays and a 4-META bonding system, together with dietary counselling, have provided a satisfactory result over 4 years.


Effects of orexin A on PTGS2, PTGES, CBR1 and PGFS mRNA transcript abundances and prostaglandin E2 and F2α concentrations in culture medium of pig uterine explants collected during early gestation and the estrogenic cycle.
In this study, aims were to evaluate orexin A (OXA) effects on mRNA abundance of important enzymes involved in prostaglandin production, such as cyclooxygenase 2 (PTGS2), microsomal PGE2 synthase-1 (PTGES), PGF2α synthase (PGFS) and carbonyl reductase 1 (CBR1), as well as prostaglandin E2 (PGE2) and F2α (PGF2α) culture medium concentrations for endometrial and myometrial explants. Tissues were collected from gilts during specific phases of the estrogenic cycle or early gestational period. There were greater concentrations of PGE2 with OXA treatments of endometrial tissues collected on days 12-13 and 27-28, as well as PGF2α on days 10-11 of the gestational period. The PGF2α concentrations were less in tissues collected on days 27-28 of the gestational period. The OXA treatments resulted in lesser concentrations of PGE2 from myometrial tissues collected on days 10-11 and greater PGF2α on days 10-11 of the gestational period and 10-11 of the estrogenic cycle. Effects of OXA may occur due to actions at PTGS2, PTGES, PGFS and CBR1 genes because mRNA abundances for proteins encoded by these genes were affected by OXA. Results indicate there is an OXA effect on mRNA abundances and prostaglandin culture medium concentrations of uterine tissue collected at different stages of the gestational period or estrogenic cycle using different doses of OXA. It, therefore, is concluded OXA may affect de novo synthesis and secretion of PGE2 and PGF2α in the uterus of pigs.


Synergistic Catalysis of Ionic Brønsted Acid and Photosensitizer for a Redox Neutral Asymmetric α-Coupling of N-Arylaminomethanes with Aldimines.
A redox neutral, highly enantioselective coupling between N-arylaminomethanes and N-sulfonyl aldimines was developed by harnessing the efficient catalysis of P-spiro chiral arylaminophosphonium barfate and a transition-metal photosensitizer under visible light irradiation. This mode of synergistic catalysis provides a powerful strategy for controlling the bond-forming processes of reactive radical intermediates.


Association Between Personality Traits and Onabotulinumtoxin A Response in Patients With Chronic Migraine.
The aim of this study was to analyze the potential association between personality traits and onabotulinumtoxin A (onabotA) response in patients with chronic migraine (CM). Previous studies from a categorial perspective show that patients with CM have anxious or obsessive personality according to the Salamanca screening test. However, the influence of personality traits in onabotA response in patients with CM has not yet been studied. We hypothesize that cluster C personality traits may be associated with non-response to onabotA. This case-control observational study includes patients with CM who received at least 2 treatment cycles of onabotA in 2 headache units between January and May 2018. onabotA response was defined as a reduction of at least 50% in the number of monthly migraine days. Personality traits were evaluated using the Salamanca questionnaire, a validated categorial inventory assessing 11 personality traits. One hundred and twelve patients, 100/112 (89.6%) females, mean age (standard deviation): 43 (11) years, were recruited. 96/112 (85.7%) achieved response to onabotA. Dependent trait was significantly associated with non-response to onabotA (P = .008; OR: 0.223 [95%CI: 0.074 to 0.675]). Significant association with other personality traits or confounders was not found. To the best of our knowledge, this is the first study showing personality traits may predict onabotA response in patients with CM. The presence of dependent personality trait in patients with CM is associated with non-response to onabotA.


Reduced expression of the μ opioid receptor in some, but not all, brain regions in mice with OPRM1 A112G.
OPRM1 A118G is a common single nucleotide polymorphism (SNP) in the coding region of the human mu opioid receptor (MOPR) gene OPRM1. This SNP is associated with higher morphine doses required for postoperative analgesia as well as a variety of drug addiction phenotypes. A mouse model possessing the equivalent substitution (A112G) in the Oprm1 gene was generated to facilitate mechanistic studies. Mice homozygous for the G112 allele (G/G) displayed lower antinociception to morphine compared with those homozygous for A112 allele (A/A), similar to humans, suggesting that the mice are a good model to further characterize underlying factors contributing to phenotypes associated with this SNP. Here, we compared [³H]DAMGO binding to the MOPR in the brains of A/A and G/G mice using quantitative in vitro autoradiography. A/A mice exhibited higher [³H]DAMGO binding than G/G in the cingulate, motor, and insular cortices, nucleus accumbens core and shell, hypothalamus, thalamus, amygdala, periaqueductal gray, superficial gray of superior colliculus, and ventral tegmental area. No genotype differences were observed in somatosensory cortex, caudate putamen, and hippocampus. When males and females were examined separately, A/A mice showed higher [³H]DAMGO binding than G/G mice in more brain regions in males than in females. Radioligand binding using brain membranes also showed higher [³H]DAMGO binding in the cortex and thalamus in A/A mice than G/G mice but no genotype differences in the caudate putamen or hippocampus. Thus, the A112G SNP is associated with reduced MOPR expression in some, but not all, brain regions, and appears to have some sex differences. The elevated MOPR expression in periaqueductal gray and thalamus in A/A mice are consistent with their higher antinociceptive responses to morphine. The higher MOPR levels in nucleus accumbens and/or ventral tegmental area of A/A mice is consistent with the higher morphine-induced hyperactivity and locomotor sensitization observed in these mice. Thus, these results provide some insights into the observed decreased clinical opioid potency in humans with the A118G SNP.


Prenatal nicotine exposure increases apnoea and reduces nicotinic potentiation of hypoglossal inspiratory output in mice.
We examined the effects of in utero nicotine exposure on postnatal development of breathing pattern and ventilatory responses to hypoxia (7.4 % O2) using whole-body plethysmography in mice at postnatal day 0 (P0), P3, P9, P19 and P42. Nicotine delayed early postnatal changes in breathing pattern. During normoxia, control and nicotine-exposed P0 mice exhibited a high frequency of apnoea (f(A)) which declined by P3 in control animals (from 6.7 +/- 0.7 to 2.2 +/- 0.7 min(-1)) but persisted in P3 nicotine-exposed animals (5.4 +/- 1.3 min(-1)). Hypoxia induced a rapid and sustained reduction in f(A) except in P0 nicotine-exposed animals where it fell initially and then increased throughout the hypoxic period. During recovery, f(A) increased above control levels in both groups at P0. By P3 this increase was reduced in control but persisted in nicotine-exposed animals. To examine the origin of differences in respiratory behaviour, we compared the activity of hypoglossal (XII) nerves and motoneurons in medullary slice preparations. The frequency and variability of the respiratory rhythm and the envelope of inspiratory activity in XII nerves and motoneurons were indistinguishable between control and nicotine-exposed animals. Activation of postsynaptic nicotine receptors caused an inward current in XII motoneurons that potentiated XII nerve burst amplitude by 25 +/- 5 % in control but only 14 +/- 3 % in nicotine-exposed animals. Increased apnoea following nicotine exposure does not appear to reflect changes in basal activity of rhythm or pattern-generating networks, but may result, in part, from reduced nicotinic modulation of XII motoneurons.


An alternative posterior ascending pulmonary artery treatment in lobectomy with inflammatory lymph node infiltration.
Lobectomy may be a challenging treatment option in lung cancer with inflammatory lymph node infiltration. Moreover, the en-masse lobectomy technique, which involves the simultaneous ligation or stapling of pulmonary vessels and bronchi at the hilar area, is controversial. We report the case of a 75-year-old woman who presented with lung cancer and lymph node infiltration from the posterior ascending pulmonary artery (A2) to the superior pulmonary artery (A6). A nodule was observed in her right upper lobe on chest computed tomography while treating her for a myocardial infarction 3 months prior; hence, a radical lobectomy was planned. Her main pulmonary artery could be constricted using surgical tape, but this was not possible in the peripheral pulmonary artery of the ascending A2 due to widespread lymph node infiltration. Intraoperative frozen sections confirmed the absence of metastases in the hilar lymph nodes. Pulmonary angioplasty was aborted because the cardiac function had not fully recovered from the previous procedure. The ascending A2 and upper lobe bronchus were collectively treated using an auto-stapler. Two months postoperatively, computed tomography showed no pulmonary artery aneurysm. This report highlights that the en-masse technique may be recommended as an alternative for A2 treatment during lobectomy in cases with inflammatory lymph node infiltration. Surgeons should consider switching to thoracotomy, in such cases, to avoid fatal intraoperative complications.


[Influence of plasmatic testosterone during natural history of prostate cancer: a review].
Prostate cancer (PCa) is the most common disease in male patients and it has the particularity to be androgen dependent. The aim of the current study was to provide an overview about the interest of testosterone dosage during the management of PCa regardless of the stage of the disease. PATIENTS ET METHODS: A systematic review of the literature was done from the PubMed database by searching the following key words alone or in combination: prostate cancer; testosterone; risk; aggressiveness; hormonotherapy; active surveillance; prognosis; androgen; cardiovascular risk; biochemical recurrence. The level of plasmatic testosterone depends on the moment of the day with a peak between the end of the night and in the morning. We can test either the whole testosterone level, the free testosterone level or the bioavailable testosterone. The bioavailable testosterone is more representative of the presence of androgen in tissues but a specialized laboratory is mandatory. The testosterone plasmatic rate is potentially useful during several steps of the PCa management: in localized prostate cancer cases, men with low testosterone levels are more likely to have an aggressive disease and are therefore not good candidates for active surveillance. An extensive radical prostatectomy should be considered in case of young men since these patients are more likely to recur subsequently; in advanced prostate cancer cases, a testosterone level has to be less or equal to 0.2 ng/mL to guarantee an appropriate castration when a patient is undergoing an androgen deprivation treatment. A dissociation between the trend of PSA and testosterone levels can be the starting point of the castration-resistant period of the disease. The testosterone level can bring useful information regarding the profile of PCa and its ability to evolve during the whole natural history of the disease.


Centrosome repositioning in T cells is biphasic and driven by microtubule end-on capture-shrinkage.
T cells rapidly reposition their centrosome to the center of the immunological synapse (IS) to drive polarized secretion in the direction of the bound target cell. Using an optical trap for spatial and temporal control over target presentation, we show that centrosome repositioning in Jurkat T cells exhibited kinetically distinct polarization and docking phases and required calcium flux and signaling through both the T cell receptor and integrin to be robust. In "frustrated" conjugates where the centrosome is stuck behind the nucleus, the center of the IS invaginated dramatically to approach the centrosome. Consistently, imaging of microtubules during normal repositioning revealed a microtubule end-on capture-shrinkage mechanism operating at the center of the IS. In agreement with this mechanism, centrosome repositioning was impaired by inhibiting microtubule depolymerization or dynein. We conclude that dynein drives centrosome repositioning in T cells via microtubule end-on capture-shrinkage operating at the center of the IS and not cortical sliding at the IS periphery, as previously thought.


Conserved chromosomal location and genomic structure of human and mouse fatty-acid amide hydrolase genes and evaluation of clasper as a candidate neurological mutation.
Fatty-acid amide hydrolase (FAAH) is a membrane-bound enzyme that degrades neuromodulatory fatty acid amides, such as oleamide and anandamide, and is expressed in the mammalian central nervous system. To evaluate FAAH genes as candidates for neurogenetic diseases in humans and mice, we have mapped the loci in both species and have determined their intron-exon structures. The human FAAH gene was mapped to region 1p34-p35, closely linked to D1S197 and D1S443, by using PCR analysis of somatic cell hybrid (SCH) and radiation hybrid mapping panels. Analysis of an SCH mapping panel and a mouse interspecific backcross panel has localized the Faah gene to the conserved syntenic region on mouse chromosome 4, close to the neurological mutation clasper. Faah gene rearrangements were excluded by Southern blot analysis of clasper DNA. No sequence abnormality was detected in PCR products containing the 15 exons and splice junctions of the mouse Faah gene. FAAH protein levels were normal in clasper mouse tissues as determined by enzyme activity assays and Western blotting.


Out-of-focus background subtraction for fast structured illumination super-resolution microscopy of optically thick samples.
We propose a structured illumination microscopy method to combine super resolution and optical sectioning in three-dimensional (3D) samples that allows the use of two-dimensional (2D) data processing. Indeed, obtaining super-resolution images of thick samples is a difficult task if low spatial frequencies are present in the in-focus section of the sample, as these frequencies have to be distinguished from the out-of-focus background. A rigorous treatment would require a 3D reconstruction of the whole sample using a 3D point spread function and a 3D stack of structured illumination data. The number of raw images required, 15 per optical section in this case, limits the rate at which high-resolution images can be obtained. We show that by a succession of two different treatments of structured illumination data we can estimate the contrast of the illumination pattern and remove the out-of-focus content from the raw images. After this cleaning step, we can obtain super-resolution images of optical sections in thick samples using a two-beam harmonic illumination pattern and a limited number of raw images. This two-step processing makes it possible to obtain super resolved optical sections in thick samples as fast as if the sample was two-dimensional.


Telothelepodidae, Thelepodidae and Trichobranchidae (Annelida, Terebelliformia) from Lizard Island, Great Barrier Reef, Australia.
In a survey of the polychaetes of the Lizard Island region, six species of polychaetes belonging to the families Telothelepodidae Nogueira, Fitzhugh & Hutchings, 2013, Thelepodidae Hessle, 1917 and Trichobranchidae Malmgren, 1866 were found, from material collected during the Lizard Island Polychaete Taxonomic Workshop, and material collected by previous projects undertaken by the Australian Museum. This material includes one new species of Rhinothelepus Hutchings, 1974 (Telothelepodidae); one new species of each of the genera, Euthelepus McIntosh, 1885, Streblosoma Sars, 1872, and Thelepus Leuckart, 1849 (Thelepodidae); and one new species of Terebellides Sars, 1835 and another of Trichobranchus Malmgren, 1866 (Trichobranchidae). Keys for identification of these species are provided, together with full descriptions for all species, as well as comparisons with the morphologically most similar congeners.


Spectrophotometric determination of L-cysteine by using polyvinylpyrrolidone-stabilized silver nanoparticles in the presence of barium ions.
In this article a simple and selective colorimetric probe for cysteine determination using silver nano particles (AgNPS) is described. The determination process was based upon the surface plasmon resonance properties of polyvinylpyrrolidone-stabilized AgNPS. Interaction of AgNPS with cysteine molecules in the presence of barium ions induced a red shift in the surface plasmon resonance (SPR) maximum of AgNPs, as a result of nanoparticle aggregation. Consequently, yellow color of AgNP solution was changed to pink. The linear range for the determination of cysteine was 3.2-8.2 μM (R=0.9965) with a limit of detection equal to 2.8 μM (3σ). The proposed method was successfully applied to the determination of cysteine in human plasma samples. Acceptable recovery results of the spiked samples confirmed the validity of the proposed method.