Tumor necrosis factor receptor-associated factor 3 is a critical regulator of B cell homeostasis in secondary lymphoid organs.
Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an adaptor protein that directly binds to a number of receptors of the tumor necrosis factor receptor (TNF-R) superfamily. Despite in vitro evidence that TRAF3 plays diverse roles in different cell types, little is known about the in vivo functions of TRAF3. To address this gap in knowledge and to circumvent the early lethal effect of TRAF3 null mutations, we generated conditional TRAF3-deficient mice. B-cell-specific Traf3(-/-) mice displayed severe peripheral B cell hyperplasia, which culminated in hyperimmunoglobulinemia and increased T-independent antibody responses, splenomegaly and lymphadenopathy. Resting splenic B cells from these mice exhibited remarkably prolonged survival ex vivo independent of B cell activating factor and showed increased amounts of active nuclear factor-kappaB2 but decreased amounts of nuclear protein kinase Cdelta. Furthermore, these mice developed autoimmune manifestations as they aged. These findings indicate that TRAF3 is a critical regulator of peripheral B cell homeostasis and may be implicated in the regulation of peripheral self-tolerance induction.


Friedman and Quade tests: BASIC computer program to perform nonparametric two-way analysis of variance and multiple comparisons on ranks of several related samples.
Friedman and Quade tests are nonparametric two-way analyses of variance which may be used to compare several related samples. The Friedman test is a multisample extension of the sign test while the Quade test is an extension of the Wilcoxon signed-rank for paired samples to the case of several related samples. The Quade test may be more powerful for a small number of treatments while the Friedman test may be more powerful when the number of treatments is five or more. The present program is written in an elementary subset of BASIC and will perform the Friedman and Quade tests quickly on practically every computer programmable in BASIC. It may i.e. be used to analyze biomedical data where the response of experimental subjects to a stimulus is monitored at time intervals.


Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health.
Maintenance of glycolytic metabolism is postulated to be required for health of the spinal column. In the hypoxic tissues of the intervertebral disc and glycolytic cells of vertebral bone, glucose is metabolized into pyruvate for ATP generation and reduced to lactate to sustain redox balance. The rise in intracellular H+ /lactate concentrations are balanced by plasma-membrane monocarboxylate transporters (MCTs). Using MCT4 null mice and human tissue samples, complemented with genetic and metabolic approaches, we determine that H+ /lactate efflux is critical for maintenance of disc and vertebral bone health. Mechanistically, MCT4 maintains glycolytic and tricarboxylic acid (TCA) cycle flux and intracellular pH homeostasis in the nucleus pulposus compartment of the disc, where hypoxia-inducible factor 1α (HIF-1α) directly activates an intronic enhancer in SLC16A3. Ultimately, our results provide support for research into lactate as a diagnostic biomarker for chronic, painful, disc degeneration. © 2019 American Society for Bone and Mineral Research.


Changes in the concentrations of trace elements in human milk during lactation.
Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine 18 trace elements (Ba, Be, Bi, Cd, Co, Cs, Cu, La, Li, Mn, Mo, Pb, Rb, Sb, Sn, Sr, Tl, and Zn) in 55 human milk samples from 46 healthy mothers collected during lactation periods extending to 293 days after birth. Se was quantified by hydride generation atomic absorption spectrometry (HG-AAS). To test the accuracy and the precision of the analytical procedure, milk powder reference materials (BCR 063 and BCR 150) were analyzed. The results obtained by ICP-MS and HG-AAS showed good agreement with the certified values. Whenever available, trace element concentrations determined in the human milk samples were compared to reliable literature data. The concentrations of Be (< 0.05 to 0.9 microgram/kg), Bi (< 0.09 to 2.0 micrograms/kg), Cs (1.7 to 7.7 micrograms/kg), La (< 0.05 to 3.7 micrograms/kg), Rb (440 to 1,620 micrograms/kg), and Tl (< 0.08 to 0.5 microgram/kg) are the first to be reported for human milk. The concentrations of the essential trace elements Cu (p < 0.005), Mn (p < 0.05), Mo (p < 0.0005), Se (p < 0.001), and Zn (p < 0.0005) significantly decreased and the concentrations of cobalt significantly increased (p < 0.005) in human milk during the course of lactation. All concentrations for the essential trace element tin in the human milk samples were below the method detection limit of 0.3 microgram/kg. Among the not essential and toxic elements-with the exception of Ba, Pb, and Tl-the trend toward lower concentrations with continuing lactation is much less pronounced than for the essential trace elements. With the exception of Se, the daily intakes of essential trace elements of fully breast-fed infants are considerably lower than dietary recommendations.


SOCS5 knockdown suppresses metastasis of hepatocellular carcinoma by ameliorating HIF-1α-dependent mitochondrial damage.
The Pringle maneuver (PM) is widely used during hepatocellular carcinoma (HCC) resection. However, it inevitably leads to ischemia and hypoxia, which promotes tumor metastasis. In this study, immunohistochemical staining of specimens from 130 HCC patients revealed that long-time PM significantly affected the prognosis of patients with high expression of suppressor of cytokine signaling 5 (SOCS5), but did not affect the prognosis of patients with low expression of SOCS5. The TCGA database showed that patients with high expression of SOCS5 had higher hypoxia scores, and it was proved that SOCS5 could promote the expression of hypoxia-inducible factor 1 subunit alpha (HIF-1α) protein by clinical tissue samples, cell experiments, lung metastases, and subcutaneous tumorigenesis experiments. Then, we used CoCl2 to construct a hypoxia model, and confirmed that SOCS5 knockdown resisted hypoxia-induced mitochondrial damage by inhibiting the expression of HIF-1α, thereby inhibiting the invasion and migration of HCC cells by immunofluorescence, electron microscopy, migration, invasion, and other experiments. We performed rescue experiments using LY294002 and rapamycin and confirmed that the knockdown of SOCS5-inhibited HCC cell invasion and migration by inhibiting the PI3K/Akt/mTOR/HIF-1α signaling axis. More importantly, we obtained consistent conclusions from clinical, cellular, and animal studies that the hypoxia-induced invasion and migration ability of SOCS5-inhibited HCC were weaker than that of normal HCC. In conclusion, we identified a novel role for SOCS5 in regulating HIF-1α-dependent mitochondrial damage and metastasis through the PI3K/Akt/mTOR pathway. The development of a SOCS5-specific inhibitor, an indirect inhibitor of HIF-1α, might be effective at controlling PM-induced tumor micrometastases during HCC resection.


Short-term colonization of fouling communities within the port of Livorno (Northern Tyrrhenian Sea, Western Mediterranean): Influence of substrate three-dimensional complexity on non-indigenous species establishment.
The influence of substrate morphology on early stages of fouling development was assessed through submerged experimental substrates with different morphological complexity. The experiment was carried out within commercial and touristic harbours of the port of Livorno (Italy), analysing the communities at three steps of colonization (14, 28, 42 days). We assessed the effect of substrate complexity on recruitment of non-indigenous species (NIS), combined with the influence of port use destinations. NIS were recorded in both use destination areas since the first step of colonization. Substrate morphological complexity significantly affected fouling colonization and particularly NIS assemblages. We found that high-complexity substrates are particularly suitable for NIS establishment in comparison with less complex ones. The touristic harbour exhibited a potential for fouling colonization higher than the commercial harbour. These results contributed to the understanding of factors involved in NIS establishment and spread, as well as in their spatial-temporal dynamics within port environments.


Attenuated alpha-gamma coupling in emotional dual pathways with right-Amygdala predicting ineffective antidepressant response.
The diversity of treatment outcomes for major depressive disorder (MDD) remains uncertain in neuropathology. The current study aimed at exploring electrophysiological biomarkers associated with treatment response. The present study recruited 130 subjects including 100 MDD patients and 30 healthy controls. All subjects participated in a sad expression recognition task while their magnetoencephalography data were recorded. Patients who had a reduction of at least 50% in disorder severity at endpoint (>2 weeks) were considered as responders. Within-frequency power and phase-amplitude coupling were measured for the brain regions involved in the emotional visual information processing pathways. The significant alpha-gamma decoupling from the right thalamus to the right amygdala in unconscious processing and from right orbital frontal cortices to the right amygdala in conscious processing was found in non-responders relative to responders and healthy controls. These kinds of dysregulation could also predict the potential treatment response. The attenuated alpha-gamma coupling in dual pathways indicated increased sensitivity to the negative emotional information and reduced moderated effect of the amygdala, which might cause insensitivity to antidepressant treatment and could be regarded as potential neural mechanisms for treatment response prediction.


[TEAM®-G (Trauma Evaluation and Management Germany). Serves as a basis for an interdisciplinary training in the emergency room].
The implementation of ATLS® in the daily routine of trauma management in the emergency department is a challenge. This goal cannot be reached by educating ATLS® to a few team members only. In order to enforce the implementation of ATLS® in a level I trauma centre, a generic in-house training was introduced in 2009 with inter-professional integration of all specialists of the trauma team. The TEAM® course (trauma evaluation and management concept of the American College of Surgeons) was the theoretical basis of the training. This educational program was developed for medical students and multidisciplinary team members. Prior training, a questionnaire for self-assessment was completed by n=84 team members to assess their knowledge about ATLS® principles. The hands-on training time was 90 min. N=10 members of the trauma team worked out three scenarios of multiple injured patients. These were provided as near-reality manikin simulations by a specialist trainer. After the training participants re-evaluated and analysed improvement by the training. Duration of trauma management and the number of missed injuries were analysed one year prior and one year after the training and served as a marker of the process and outcome quality of trauma care. Prior the training, 57% of trainees specified their knowledge related to the ATLS® can be improved. Their expectations were generally satisfied by the training. The mean time of trauma management in the ED could not be reduced one year after the training (36±16 min) compared to one year prior the training (39±18 min), however, the detection of missed injuries (5.6% vs. 3.2%, p<0.05) was significantly diminished after the training. Apart form education of ATLS® providers the inauguration of an interdisciplinary and interprofessionel team training may enhance implementation of ATLS- algorithms into daily routine.


Next-generation sequencing technology for detecting pulmonary fungal infection in bronchoalveolar lavage fluid of a patient with dermatomyositis: a case report and literature review.
Invasive fungal pneumonia is a severe infectious disease with high mortality in immunocompromised patients. However, the clinical diagnosis of the pathogen(s) remains difficult since microbiological evidence is difficult to acquire. Here, we report a case of pulmonary fungal infection detected by next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF) in a 61-year-old male with corticosteroid-treated dermatomyositis. Cytomegalovirus and influenza A virus infections were confirmed by nucleic acid detection and treated with antiviral medicine. The patient had been diagnosed with severe pneumonia and treated with empiric broad-spectrum antibacterial and antifungal drugs before bronchoscopy was performed. The patient responded poorly to those empiric treatments. Three fungi were found by NGS in the BALF, namely, Pneumocystis jirovecii, Aspergillus fumigatus and Rhizopus oryzae. After adjusting the patient's treatment plan according to the NGS results, he improved significantly. This case highlights the combined application of NGS and traditional tests in the clinical diagnosis of pulmonary invasive fungal disease. NGS is proposed as an important adjunctive diagnostic approach for identifying uncommon pathogens.


Dynamic impact of social stratification and social influence on smoking prevalence by gender: An agent-based model.
Smoking behavior is tightly related to socioeconomic status and gender, though the dynamic and non-linear association of smoking prevalence across socioeconomic status and gender groups has not been fully examined. With a special focus on gender-bound differences in the susceptibility to social influence of surrounding others' behaviors, we developed an agent-based model to explore how socioeconomic disparity between and within gender groups affects changes in smoking prevalence. Our developed base model reasonably reproduced the actual trend changes by gender groups over the past 5 years in Japan. Counterfactual experiments with the developed model revealed that closing within- and between-gender disparities in socioeconomic status had a limited impact on reducing smoking prevalence. To the contrary, greater socioeconomic disparity facilitated the reduction in prevalence among males, but it impeded that reduction in females. The counterfactual scenario with equalizing gender-bound susceptibility to social influence among women to men's level showed a dramatic reduction in female prevalence without changing the reduction in male prevalence. Simulation results may provide alternative explanation of the growing disparity in smoking prevalence despite improved welfare equality observed in many developed countries, and suggest that redistribution policies may have side effects of widening health gap. Instead, social policy to reduce social pressures to smoking and support interventions to enhance resilience to the pressure targeting the vulnerable population (in this study, women) would be a more effective strategy in combating the tobacco epidemic and closing the health gap.


Cerebral arteriovenous malformation presenting with polycythemia vera: A case report and literature review.
Cerebral arteriovenous malformations (AVM) usually present with headache, hemorrhage, or seizure. Erythropoietin (EPO) has demonstrated protective effects against ischemia within the CNS. The authors report a patient with a cerebral AVM and concurrent polycythemia associated with elevated serum EPO. Systemic EPO levels declined acutely after resection of the patient's AVM, and the polycythemia resolved in the following months. Polycythemia secondary to a cerebral AVM, in the absence of extra-cerebral vascular lesions, has not been described in the literature. The authors explore the mechanisms by which this patient's cerebral AVM could have induced EPO production within the brain, manifesting as polycythemia.


Plasma-activated water: A cutting-edge technology driving innovation in the food industry.
Innovation regarding food production and processing is required to meet the emerging challenges of ensuring worldwide food security and meeting consumer demands for high-quality, safe and nutritious food products. This review provides insights into the current state-of-the-art of the emerging applications of Plasma Activated Water (PAW) in the food industry. PAW antimicrobial properties, inactivation mechanisms and the critical factors determining the lethal effect, as well as the bases for other technological applications are discussed. Overall, this review article describes the degree of success achieved by PAW technology in different applications and illustrates its feasibility and applicability in the food-processing industry.


Granulocyte/macrophage-colony stimulating factor in allergen-induced rhinitis: cellular localization, relation to tissue eosinophilia and influence of topical corticosteroid.
Allergen-induced late nasal responses are associated with recruitment of T lymphocytes and eosinophils, and preferential messenger RNA (mRNA) expression of 'TH2-type' cytokines. We previously showed that topical steroid inhibited the late response and associated tissue eosinophilia. In this study we tested the hypothesis that granulocyte/macrophage-colony stimulating factor (GM-CSF) may contribute to late-responses and tissue eosinophilia and is inhibitable by topical corticosteroid. Nasal biopsies were taken before and 24 h after nasal allergen provocation following 6 weeks of treatment with either a nasal corticosteroid spray (fluticasone propionate) or a matched placebo nasal spray twice daily. Cryostat sections were processed by immunohistochemistry and in situ hybridization to assess cytokine mRNA expression for GM-CSF. Increases in T lymphocytes and eosinophils were seen in the nasal mucosa after allergen challenge (p = 0.01) which were accompanied by a 5-fold increase in cells expressing mRNA for GM-CSF (p = 0.01). Double immunohistochemistry/in situ hybridization demonstrated that the majority of GM-CSF mRNA+ cells were co-localized to CD68+ (40%), or T cells (40%) with a lesser contribution from eosinophils (<20%). Topical steroid treatment was accompanied by a decrease in both the CD3+ and major basic protein (MBP+) cells expressing GM-CSF mRNA (p = 0.01) with a corresponding proportionate increase in the % of macrophages expressing GM-CSF. The results indicate that after allergen provocation, eosinophils are recruited to the nasal mucosa and that, at least in part, this may be due to GM-CSF. Topical nasal corticosteroid inhibits late responses and the associated eosinophilia, possibly indirectly by decreasing GM-CSF from T lymphocytes or reducing autocrine production of GM-CSF from eosinophils.


5TH International Ancient DNA Conference. Divining diet and disease from DNA.
Some 110 scientists from a range of disciplines gathered in the overcast British midlands for the 5th International Ancient DNA Conference, held here from 12 to 14 July. Among the attractions were new insights into the diets of early Americans gleaned from ancient human coprolites and intriguing reports of nuclear DNA and ancient viral sequences extracted from mammoth bones.


Interactive effect of orthostatic hypotension on gray matter atrophy associated with hyposmia and RBD in de novo Parkinson's disease.
Orthostatic hypotension (OH) is a potential modifiable risk factor for cognitive impairment in patients with Parkinson's disease (PD). Although other risk factors for dementia, hyposmia and REM sleep behavior disorder (RBD), are closely associated with autonomic dysfunction in PD, little is known about how these risk factors influence cognitive function and cerebral pathology. We investigated how these three factors contribute to gray matter atrophy by considering the interaction of OH with hyposmia and RBD. We analyzed cortical thickness, subcortical gray matter volume, and cognitive measures from 78 patients with de novo PD who underwent the head-up tilt test for the diagnosis of OH. Whole-brain analyses with Monte Carlo corrections revealed that hyposmia was associated with decreased cortical thickness in a marginal branch of the cingulate sulcus among patients with OH, and cortical thickness in this area correlated with cognitive functioning only in patients with OH. Subcortical gray matter volume analysis indicated that severe RBD was associated with decreased volume in the left hippocampus and bilateral amygdala among patients with OH. Even in early PD, OH exerts effects on gray matter atrophy and cognitive dysfunction by interacting with RBD and hyposmia. OH might exacerbate cerebral pathology induced by hyposmia or RBD.


Nanoclay Promotes Mouse Cranial Bone Regeneration Mainly through Modulating Drug Binding and Sustained Release.
Nanoclay (Nanosilicates, NS) is appearing as an intriguing 2D nanomaterial for bone tissue engineering with multiple proposed functions, e.g., intrinsic osteoinductivity, improving mechanical properties, and drug release capacity. However, the mechanism of NS for in vivo bone regeneration has been hardly defined so far. This knowledge gap will significantly affect the design/application of NS-based biomaterials. To determine the role of NS in osteoblastic differentiation and bone formation, we used the mouse calvarial-derived pre-osteoblasts (MC3T3-E1) and a clinically-relevant mouse cranial bone defect model. Instead of a hydrogel, we prepared biomimetic 3D gelatin nanofibrous scaffolds (GF) and NS-blended composite scaffolds (GF/NS) to determine the essential role of NS in critical low-dose (0.5 μg per scaffold) of BMP2-induced cranial bone regeneration. In contrast to "osteoinductivity", our data indicated that NS could enable single-dose of BMP2, promoting significant osteoblastic differentiation while multiple-dose of BMP2 (without NS) was required to achieve similar efficacy. Moreover, our release study revealed that direct binding to NS in GF scaffolds provided stronger protection to BMP2 and sustained release compared to GF/NS composite scaffolds. Consistently, our in vivo data indicated that only BMP2/NS direct binding treatment was able to repair the large mouse cranial bone defects after 6 weeks of transplantation while neither BMP2, NS alone, nor BMP2 released from GF/NS scaffolds was sufficient to induce significant cranial bone defect repair. Therefore, we concluded that direct nanoclay-drug binding enabled sustained release is the most critical contribution to the significantly improved bone regeneration compared to other possible mechanisms based on our study.


Ubiquitin-based pathway acts inside chloroplasts to regulate photosynthesis.
Photosynthesis is the energetic basis for most life on Earth, and in plants it operates inside double membrane-bound organelles called chloroplasts. The photosynthetic apparatus comprises numerous proteins encoded by the nuclear and organellar genomes. Maintenance of this apparatus requires the action of internal chloroplast proteases, but a role for the nucleocytosolic ubiquitin-proteasome system (UPS) was not expected, owing to the barrier presented by the double-membrane envelope. Here, we show that photosynthesis proteins (including those encoded internally by chloroplast genes) are ubiquitinated and processed via the CHLORAD pathway: They are degraded by the 26S proteasome following CDC48-dependent retrotranslocation to the cytosol. This demonstrates that the reach of the UPS extends to the interior of endosymbiotically derived chloroplasts, where it acts to regulate photosynthesis, arguably the most fundamental process of life.


Comparison of radical-driven technologies applied for paraben mixture degradation: mechanism, biodegradability, toxicity and cost assessment.
Parabens (esters of p-hydroxybenzoic acid) are xenobiosis belonging to endocrine disruptors and commonly used as a preservative in cosmetics, food, pharmaceutical, and personal care products. Their wide use is leading to their appearance in water and wastewater in the range from ng/L to mg/L. In fact, the toxicity of benzylparaben is comparable to bisphenol A. Therefore, it is important to find not only effective but also ecofriendly methods for their removal from aqueous environment since the traditional wastewater treatment approaches are ineffective. Herein, for the first time, such extended comparison of several radical-driven technologies for paraben mixture degradation is presented. The detailed evaluation included (1) comparison of ozone and hydroxyl peroxide processes; (2) comparison of catalytic and photocatalytic processes (including photocatalytic ozonation); (3) characterisation of catalysts using SEM, XRD, DRS, XPS techniques and BET isotherm; (4) mineralisation, biodegradability and toxicity assessment; and (5) cost assessment. O3, H2O2/Fe2+, H2O2/UVC, O3/H2O2, O3/UVA, O3/H2O2/UVA, UVA/catalyst, O3/catalyst and O3/UVA/catalyst were selected from advanced oxidation processes to degrade parabens as well as to decrease its toxicity towards Aliivibrio fischeri, Corbicula fluminea and Lepidium sativum. Research was focused on the photocatalytic process involving visible light (UVA and natural sunlight) and TiO2 catalysts modified by different metals (Ag, Pt, Pd, Au). Photocatalytic oxidation showed the lowest efficiency, while in combining ozone with catalysis and photocatalysis process, degradation efficiency and toxicity removal were improved. Photocatalytic ozonation slightly improved degradation efficiency but appreciably decreased transferred ozone dose (TOD). Results indicate that the degradation pathway is different, or different transformation products (TPs) could be formed, despite that the hydroxyl radicals are the main oxidant. Graphical abstract.


Evidence-based clicker use: Audience Response Systems for rehabilitation nurses.
An Audience Response System (ARS) commonly used in schools and universities was studied for its benefit in rehabilitation. Audience response systems or "clickers" are technological tools for promoting interactive learning. Clickers were studied for their applicability to clinical settings as well. Current literature shows evidence-based research and best practices for clicker use within schools. This study expanded ARS into the rehabilitation milieu and then analyzed learner opinions and outcomes. Qualitative data was obtained from both professional and patient groups. Clickers were used while presenting research findings at conferences, when conducting staff seminars, and during client support groups and subsequent educational sessions. Response graphs and decision trees illustrate the flexibility of ARS for helping educators match presentation content to audience feedback. Clickers narrowed the gap between those with expertise and those with minimal experience, since immediate clarification was given according to clicker results. ARS helped to engage listeners, which is consistent with clicker research conducted in academic environments. With clickers, the knowledge and viewpoints of participants can be instantly graphed and displayed, and pertinent information can be provided in real-time. Examples from rehabilitation scenarios depict benefits of Audience Response Systems beyond academia.


Cancer immunotherapy and immune-related response assessment: The role of radiologists in the new arena of cancer treatment.
The recent advances in the clinical application of anti-cancer immunotherapeutic agents have opened a new arena for the treatment of advanced cancers. Cancer immunotherapy is associated with a variety of important radiographic features in the assessments of tumor response and immune-related adverse events, which calls for radiologists' awareness and in-depth knowledge on the topic. This article will provide the state-of-the art review and perspectives of cancer immunotherapy, including its molecular mechanisms, the strategies for immune-related response assessment on imaging and their pitfalls, and the emerging knowledge of radiologic manifestations of immune-related adverse events. The cutting edge clinical and radiologic investigations are presented to provide future directions.


A comparison of ranitidine, droperidol or placebo in the prevention of nausea and vomiting after hysterectomy.
The effect of ranitidine on postoperative nausea and vomiting (PONV) was assessed when compared with droperidol and with placebo. Three groups of sixty patients were studied in a double-blind randomized manner. The first group received ranitidine tablets 300 mg on the night before and on the following morning, one hour before induction of anaesthesia. Thirty minutes before surgery ended they were given isotonic saline 0.3 ml iv. The second group had placebo in place of ranitidine while before the operation ended, droperidol 0.75 mg (0.3 ml) was injected. The third group received placebos rather than the study drugs. The immediate two-hour postoperative recovery room period and that on the ward were evaluated until the next morning. PONV information was gathered from complaints by the patients and from direct questioning by the nursing staff. Droperidol 0.75 mg iv served as the "rescue drug." Less PONV occurred in patients who received anti-emetics than those given placebo: recovery room, P = 0.0109; ward, P = 0.007. Droperidol better suppressed PONV in the recovery room (P = 0.005) with no statistical significance seen between ranitidine and placebo. On the ward, both anti-emetics were more effective than placebo (ranitidine, P = 0.01; droperidol, P = 0.003). "Rescue drug" requirements throughout the study periods were not statistically significant. Although both anti-emetics were associated with a smaller incidence of PONV than was placebo, droperidol was superior to ranitidine in preventing sickness during the immediate postoperative period. The need for the "rescue drug" was similar in all groups.


Two-dimensional and three-dimensional multiple object tracking learning performance in adolescent female soccer players: The role of flow experience reflected by heart rate variability.
Three-dimensional multiple object tracking (3D-MOT) has been used in various fields to mimic real-life tracking, especially in perceptual-cognitive skills training for soccer. Yet, the learning efficiency in 3D-MOT tasks has not been compared with 2D-MOT. Further, whether the advantage can be reflected by heart rate variability (HRV) based on the neurovisceral integration model should also be examined. Therefore, we used both 2D- and 3D-MOT in a brief adaptive task procedure for adolescent female soccer players with HRV measurement. A faster tracking speed threshold of participants was found in the 3D- compared to 2D-MOT, as well as average tracking speed in the last training period of 3D-MOT. Moreover, lower low frequency (LF) components of HRV in the 3D-MOT indicated a flow experience, demonstrating the provision of more attentional resources. Therefore, we observed that adolescent female soccer players demonstrated higher learning efficiency in 3D-MOT tasks in virtual reality (VR) through a higher flow experience. This study examined the learning efficiency between the two MOT tasks in the soccer domain using evidence from HRV and highlighted the utility and applicability of 3D-MOT application.


Urethroperineal-rectal fistula in Crohn's disease.
A 19-year-old white male with Crohn's disease, who complained of passing urine per rectum and having retrograde ejaculations, was noted to have a urethroperineal-rectal fistula. The fistulous communication remained patent despite pharmacologic therapy, a diversion ileostomy, and a total proctocolectomy. A fistulectomy and definitive urethral repair finally resulted in resolution of the problem.


Changes in the down colour of chicks during a population decline in red grouse.
Difficulties in using genetic markers to demonstrate that changes in gene frequency cause fluctuations in the density of animal populations are illustrated. The frequency of chicks with light-coloured down increased during 4 years when population density of red grouse declined and the inherent level of aggressive behaviour of adults increased. Variations in aggressive behaviour and down colour of individuals within years, however, were not related.


[Diagnostic workup of brain-dead organ donors and organ retrieval].
Renal transplantation is well established as the best and often the only treatment for many patients with end-stage kidney failure. Because of an increasing shortfall between the diminishing number of deceased donor organs available and the increasing waiting list of patients in need of transplantation the shortage of suitable donors remains one of the most pressing challenges. The success of organ transplantation can be attributed to many factors but ultimately depends upon retrieval and preservation techniques to maintain the quality of an organ. Although the literature on organ retrieval is extensive, the level of evidence provided is mainly low. But as techniques and treatments improve, it may be possible to use organs from donors who were previously thought to be unsuitable. This article provides the reader an overview on the topic of organ donation.


Effect of chemical composition of coal ash used to prepare granulated coal ash on the removal of hydrogen sulfide from water.
Granulated coal ash was prepared by mixing coal ash derived from a coal electric power plant and blast furnace cement, to remove hydrogen sulfide from aquatic environment. In this study, we investigate the effects of the composition of the coal ash used to prepare the granulated coal ash on its hydrogen sulfide removal performance. Manganese, magnesium, and calcium contents in the granulated coal ash were found to be the major factors in controlling the rate of hydrogen sulfide removal. The kinetics of hydrogen sulfide removal by the granulated coal ash were expressed as a first-order equation with a rate constant of 0.0081-0.080 h-1 . The rate constant for hydrogen sulfide removal obtained in this study correlated well with the manganese content in the granulated coal ash. The increasing surface pH attributed to the hydrolysis of calcium and magnesium on the surface of the granulated coal ash slightly increased the hydrogen sulfide removal rate. PRACTITIONER POINTS: Adsorbents for H2 S are prepared by coal ash from different coal blend and coal electric power generation processes. Adsorbents tested in this study could remove hydrogen sulfide effectively. Manganese oxide in the adsorbents enhanced the removal rate of hydrogen sulfide. Adsorbents tested in this study contribute to sustainable development goals in terms of coal fly ash recycling.


Gastrointestinal manifestations of scleroderma.
Gastrointestinal involvement is commonly found in scleroderma. Gastrointestinal symptoms may be the presenting symptoms for the diagnosis and may precede the actual diagnosis by months to years. The esophagus is the most frequently affected, but functional problems of the anorectum, small bowel, colon, and stomach may occur. The pathophysiologic mechanism appears to be one of smooth muscle atrophy and, to a lesser degree, fibrosis. These changes result in gastrointestinal motility disturbances and may cause GERD, pseudo-obstruction, bacterial overgrowth, and defecatory disorders. Malnutrition may be a serious consequence. The evaluation of a particular symptom in a patient with scleroderma may lead to treatment strategies that improve the patient's sense of well-being and quality of life.


Functions and mechanisms of protein lysine butyrylation (Kbu): Therapeutic implications in human diseases.
Post-translational modifications (PTM) are covalent modifications of proteins or peptides caused by proteolytic cleavage or the attachment of moieties to one or more amino acids. PTMs play essential roles in biological function and regulation and have been linked with several diseases. Modifications of protein acylation (Kac), a type of PTM, are known to induce epigenetic regulatory processes that promote various diseases. Thus, an increasing number of studies focusing on acylation modifications are being undertaken. Butyrylation (Kbu) is a new acylation process found in animals and plants. Kbu has been recently linked to the onset and progression of several diseases, such as cancer, cardiovascular diseases, diabetes, and vascular dementia. Moreover, the mode of action of certain drugs used in the treatment of lymphoma and colon cancer is based on the regulation of butyrylation levels, suggesting that butyrylation may play a therapeutic role in these diseases. In addition, butyrylation is also commonly involved in rice gene expression and thus plays an important role in the growth, development, and metabolism of rice. The tools and analytical methods that could be utilized for the prediction and detection of lysine butyrylation have also been investigated. This study reviews the potential role of histone Kbu, as well as the mechanisms underlying this process. It also summarizes various enzymes and analytical methods associated with Kbu, with the goal of providing new insights into the role of Kbu in gene regulation and diseases.


Enabling Secure Data sharing with data deduplication and sensitive information hiding in cloud-assisted Electronic Medical Systems.
Data sharing is very important for medical researchers to do research on certain diseases in cloud-assisted electronic medical systems. Nonetheless, there are large amounts of duplicate data in shared electronic medical records, which incurs redundant storage. In addition, data sharing of electronic medical records might expose the sensitive information of patients. In order to address above problems, we propose a secure data sharing scheme with data deduplication and sensitive information hiding in cloud-assisted electronic medical systems in this paper. In order to protect the sensitive information privacy and enhance the deduplication efficiency, we replace the patient's sensitive information of electronic medical records by wildcards before encrypting the whole electronic medical records. The authorized researcher can decrypt and obtain the electronic medical records under the condition that the sensitive information of shared electronic medical records is hidden. Moreover, we clarify the diagnose information of the electronic medical records into different types according to the duplicate ratio. The authorized researchers can selectively download data according to the duplicate ratio of diagnostic information. Our proposed scheme can resist brute-force attacks and single-point-of-failure attack. The experimental results show our proposed scheme is more efficient than the existing schemes.


Symptomatic nonparasitic liver cysts.
Based on our experience with four cases of liver cysts and review of the literature, the following conclusions are reached: (1) Diagnosis can be established with routine and special radiologic studies. (2) Laparotomy is indicated for patients with symptoms or uncertain diagnosis. (3) Surgical management should be guided by cyst size, location, and content. (4) Definitive surgical treatment is indicated only for cysts larger than 10 cm.


Complementary and alternative medicine in patients with inflammatory bowel disease: A survey performed in a tertiary center in Chile.
The aim of this study was to assess the type and prevalence of complementary and alternative medicine (CAM) use in patients with inflammatory bowel disease (IBD) who are treated at our center. Observational, cross-sectional questionnaire-based study that included patients from the IBD program of our center. Tertiary clinical center in Santiago, Chile. Types of CAM being used by patients with IBD. A total of 200 patients were included, 68% ulcerative colitis, 29% Crohn's disease, and 3% non-classifiable IBD. Overall, 25% of the patients reported current use of CAM, 30% reported using in it the past, and 45% indicated that they had never used it before. The use of CAM was recommended in 20% of the patients by other healthcare professionals and in 10% of the patients by the gastroenterologist. Forty-nine percent of the patients informed the gastroenterologist that they were using CAM. Overall, 86% of the patients did not modify the conventional medical treatment (CMT). None of the patients who were using curcumin, homeopathic medicine, acupuncture or biomagnetism modified the CMT. The type of CAM being used plays an important role when the patient makes the decision to inform the gastroenterologist. Other healthcare professionals play an important role in providing the advice to start CAM. Gastroenterologists must be aware of the high prevalence of CAM use in IBD patients, actively ask about CAM use and guide the patients who want to use CAM in a responsible and safe manner.


The role of capsule aperture size on the dispersion of carrier-based formulation at different air flowrates.
The effect of capsule aperture size on the aerosol performance of lactose blend formulation was studied using Foradil® (containing 12 μg of formoterol fumarate (FF1) and 24 mg of lactose) dispersed with a powder inhaler Aerolizer® at increasing air flowrates. Apertures sizes of 0.4, 1.0, 1.5, 2.5, and 4.0 mm were introduced at the opposite ends of the capsule. The formulation was dispersed into a Next Generation Impactor (NGI) at 30, 60 and 90 L/min, with the fine particle fractions (FPFrec and FPFem) measured by chemical assay of FF and lactose using high-performance liquid chromatography. Particle size distribution (PSD) of FF particles dispersed in wet media was also characterized by laser diffraction. FPFrec showed a stronger dependency on the flowrate than the capsule aperture size. The most efficient dispersion was achieved at 90 L/min. At a given flowrate, FPFem remained broadly constant across different aperture sizes. The laser diffraction studies demonstrated the presence of large agglomerates.


Behavioral responses by bumble bees to variation in pollen availability.
Pollen-collecting bumble bees (Bombus spp.) detect differences between individual flowers in pollen availability and alter their behavior to capitalize on rewarding flowers. Specific responses by bees to increased pollen availability included: longer visits to flowers; visits to more flowers within an inflorescence, including an increased frequency of revisits; an increased likelihood of grooming while the bee flow between flowers within the inflorescence; and more protracted inter-flower flights, probably because of longer grooming bouts. The particular suite of responses that a bee adopted depended on the pollen-dispensing mechanism of the plant species involved. Bees buzzed previously-unvisited Dode-catheon flowers longer than empty flowers. In contrast, pollen availability did not significantly affect the duration of visits to Lupinus flowers, which control the amount of pollen that can be removed during a single visit. Simulation results indicate that the observed movement patterns of bumble bees on Lupinus inflorescences would return the most pollen per unit of expended energy. The increased foraging efficiency resulting from facultative responses by bees to variation in pollen availability, especially changes in the frequency and intensity of grooming, could correspondingly decrease pollen dispersal between plants.


The preferred magnetic resonance imaging planes in quantifying visceral adipose tissue and evaluating cardiovascular risk.
Magnetic Resonance Imaging (MRI) is a well-accepted non-invasive method in the quantification of visceral adipose tissue. However, a standard method of measurement has not yet been universally agreed. The objectives of the present study were 2-fold, firstly, to identify the imaging plane in the Chinese population which gives the best correlation with total visceral adipose tissue volume and cardiovascular risk factors; and secondly to compare the correlations between single-slice and multiple-slice approach with cardiovascular risk factors. Thirty-seven Chinese subjects with no known medical history underwent MRI examination for quantifying total visceral adipose tissue volume. The visceral adipose tissue area at five axial imaging levels within abdomen and pelvis were determined. All subjects had blood pressure measured and fasting blood taken for analysis of cardiovascular risk factors. Framingham risk score for each subject was calculated. The imaging plane at the level of 'lower costal margin' (LCM) in both men and women had the highest correlation with total visceral adipose tissue volume (r = 0.97 and 0.99 respectively). The visceral adipose tissue area at specific imaging levels showed higher correlations with various cardiovascular risk factors and Framingham risk score than total visceral adipose tissue volume. The visceral adipose tissue area at 'umbilicus' (UMB) level in men (r = 0.88) and LCM level in women (r = 0.70) showed the best correlation with Framingham risk score. The imaging plane at the level of LCM is preferred for reflecting total visceral adipose tissue volume in Chinese subjects. For investigating the association of cardiovascular risk with visceral adipose tissue in MRI-obesity research, the single-slice approach is superior to the multiple-slice approach, with the level of UMB in men and LCM in women as the preferred imaging planes.


Rupture of flexor digitorum profundus to the index finger after a distal radial fracture.
Attrition ruptures of flexor tendons to the fingers following Colles' fractures are very rare. In the case reported here, a protruding bony fragment caused a delayed rupture of the flexor digitorum profundus tendon to the index finger one year after a fracture of the distal end of the radius. Suture of the distal end of the tendon to the adjacent profundus tendon two years after the fracture produced a successful result.


Thalassemia and pregnancy: results of an antenatal screening program.
A thalassemia screening program was implemented at our institution using the finding of a mean corpuscular volume less than 80 fl as the index of abnormality. Further evaluation using hemoglobin (Hb) electrophoresis and serum iron studies was carried out according to the scheme detailed below. A diagnosis of thalassemia was made in 33 women (42 pregnancies). Eight patients had alpha-thalassemia trait, 23 beta-thalassemia trait, and two Hb H disease. Thalassemia trait did not have any adverse effect on pregnancy outcome. In two couples the fetuses were at risk for homozygous disease and in one couple the fetus was at risk for sickle cell beta-thalassemia. The screening program described is an effective and inexpensive means of detecting thalassemia in an antenatal population and is applicable to most every clinic or office setting.


Intertrochanteric fractures of the femur: a prospective study comparing the use of the Küntscher-Y nail and a sliding hip screw.
This prospective randomized study has compared the use of the Küntscher-Y nail and a sliding hip screw in the treatment of intertrochanteric fractures of the femur. For patients whose general health was good, the use of the sliding hip screw was associated with a significantly lower 1-year mortality rate. The use of the sliding screw also resulted in a higher proportion of 1-year survivors regaining their prefracture level of mobility. There was no difference in the rates of cutting-out of the two implants but use of the Küntscher-Y nail was associated with a greater incidence of shortening.


The varieties of depressive experience: diagnosing mood disorders.
Biopsychosocial eclecticism has led, the authors believe, to a simplistic acceptance of a unitary view of MDD with little scientific solidity. The authors propose a return to careful psychopathology as the basis of all nosology, which has led to identifying four main types of depressive illness, and a method-based, existential approach to understanding depression.


A large-scale study of microplastic abundance in sediment cores from the UK continental shelf and slope.
To inform risk assessments, reliable, time efficient and affordable quantification methods are required for creating a microplastic (MP) pollution baseline in the world's oceans. To facilitate this, MP abundance was investigated in sediments of three contrasting areas of the UK continental shelf: North West of Jones Bank, the Canyons in the Celtic Sea and Dogger Bank in the North Sea, utilising the Nile Red tagging method to assess its time efficiency and cost. Average MP abundance in the top 10 cm was 1050-2700 MP kg-1. MP abundance decreased with increasing sediment depth and increased with increasing water depth. The findings emphasise the extent of MP pollution and illustrate the value of Nile Red for large scale mapping at relatively low cost.


Associations between obesity and asthma in a low-income, urban, minority population.
Community-based studies of obesity, asthma, biomarkers of oxidative stress, and adipokines among low-income, urban, minority populations are lacking. Oxidative stress, perhaps modulated by adipokines, may increase airway inflammation in obese individuals. To characterize associations between obesity and asthma in a low-income, urban, minority community and evaluate adipokines, biomarkers of inflammation, and oxidant-antioxidant balance in association with asthma and obesity. A door-to-door evaluation of asthma and obesity prevalence was performed in a low-income housing development. Nonsmoking adults and children underwent additional evaluation, including allergy skin testing, and measures of serum adipokines, and indicators of oxidative stress in blood and exhaled breath. The prevalences of current asthma and a body mass index in the 85th percentile or higher were 15.8% and 35.3%, respectively, among 350 nonsmokers older than 4 years. Asthma and obesity were not associated with one another (odds ratio, 1.0; 95% confidence interval, 0.55-1.84). Among 116 nonsmoking participants who underwent biomarker evaluation, obesity was not associated with exhaled nitric oxide. In multivariate logistic models that adjusted for age category, sex, and a body mass index in 85th percentile or higher, leptin concentrations in the highest quartile were associated with asthma (odds ratio, 8.34; 95% confidence interval, 1.29-50.2) but not with atopy. Adiponectin was associated with total antioxidant capacity in exhaled breath. Asthma and obesity, although both common in a low-income, minority community, were not associated with one another. Nevertheless, adipokines were associated with asthma status and with markers of oxidative stress in the lungs, providing some support for an adipokine-inflammatory mechanistic link between the two conditions.


Rare royal families in honeybees, Apis mellifera.
The queen is the dominant female in the honeybee colony, Apis mellifera, and controls reproduction. Queen larvae are selected by the workers and are fed a special diet (royal jelly), which determines caste. Because queens mate with many males a large number of subfamilies coexist in the colony. As a consequence, there is a considerable potential for conflict among the subfamilies over queen rearing. Here we show that honeybee queens are not reared at random but are preferentially reared from rare "royal" subfamilies, which have extremely low frequencies in the colony's worker force but a high frequency in the queens reared.


Acetazolamide Attenuates Thrombin-Induced Hydrocephalus.
Our previous studies demonstrated that thrombin is an important factor in brain injury after intracerebral and intraventricular hemorrhage. This study examined the effect of acetazolamide, a carbonic anhydrase inhibitor, on thrombin-induced hydrocephalus. There were two parts in this study. First, rats had an injection of either 50 μl saline or 3 U thrombin into the right lateral ventricle. Second, rats had an injection of 3 U thrombin into the right lateral ventricle and were treated with either vehicle or acetazolamide (30 mg/kg, intraperitoneally (IP)) at 1 h after thrombin infusion. Lateral ventricle volumes were measured in magnetic resonance imaging T2 images and the brains were used for histology analysis at 24 h later. Intraventricular injection of thrombin induced significantly larger ventricle volume (27.8 ± 3.7 vs 8.5 ± 1.3 mm(3), n = 6, p < 0.01) and more ventricular wall damage (the breakdown of the ependymal layer, 20.2 ± 3.1 vs 2.4 ± 0.8 %, n = 6, p < 0.01) compared with saline injection. Acetazolamide treatment (30 mg/kg, IP) markedly attenuated thrombin-induced hydrocephalus (16.1 ± 4.2 mm(3) vs 29.5 ± 5.3 mm(3), n = 6, p < 0.01). These results suggest decreasing CSF production by acetazolamide attenuated thrombin-induced hydrocephalus in rats.


[Ureter drugs].
Many improvements have been made recently in the field of the ureteral smooth muscle pharmacology. After a brief summary on physiological basis, we review what is known about effects on ureter of different drugs class. In a second part, we review clinical applications for renal colic analgesia, calculi expulsive medical therapy, ESWL adjuvant treatment and preoperative treatment before retrograde access. There are now sufficient data on NSAID and alpha-blockers. beta-agonists, especially for beta3 selective ones, and topical drugs before retrograde access are interesting and should be further evaluated.


Efficacy and safety of scalp acupuncture for poststroke depression: A meta-analysis and systematic review.
Poststroke depression (PSD) is a common clinical poststroke complication that adversely affects cognitive and physical function rehabilitation. Scalp acupuncture (SA) can significantly improve somatic dysfunction and emotional disorder in stroke patients. This meta-analysis aims to evaluate the effectiveness and safety of SA in the treatment of PSD. We conducted a comprehensive search of multiple electronic databases, including PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Internet, China Science and Technology Journal Database, Wan Fang Data Knowledge Service Platform, and China Biology Medicine databases until December 20, 2022, to identify randomized controlled trials investigating the efficacy of SA in the treatment of PSD. Two independent researchers screened the literature, extracted data, and assessed the risk of bias in the included studies based on the inclusion and exclusion criteria. We performed a meta-analysis of the eligible literature using RevMan 5.4.1 and Stata 15.0 software. This study comprised a total of 14 randomized controlled trials, 10 of which used SA and 4 of which used SA in combination with electroacupuncture therapy. The results of the meta-analysis revealed that the effective rate of the SA group was significantly higher than that of the Western medicine group (relative risk = 1.09, 95% confidence interval (CI) [1.02, 1.16], P = .008). Moreover, compared to the Western medicine group, the SA group demonstrated significant improvements in Hamilton depression scale scores (mean difference = -2.29, 95% CI [-3.88, -0.70], P = .005) and neurological function deficit scores (mean difference = -3.06, 95% CI [-5.91, -0.21], P = .04). Additionally, the SA group has a lower incidence of adverse events than the western medicine group (relative risk = 0.12, 95% CI [0.05, 0.29], P < .00001). SA has superior efficacy and safety compared to Western medicine for PSD. These findings suggest that SA could be a promising alternative treatment for the assessed condition. Due to the limited number and quality of the included literature, the above conclusions must be confirmed by additional high-quality research.


New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma.
The use of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) as a positron emission tomography (PET) tracer for brain tumor imaging might have some limitations because of the relatively low affinity for the L-type amino acid transporter 1 (LAT1). To assess the stereospecificity and evaluate the influence of aromatic ring modification of phenylalanine LAT1 targeting tracers, six different fluoroalkylated phenylalanine analogues were synthesized. After in vitro Ki determination, the most promising compound, 2-[18F]-2-fluoroethyl-L-phenylalanine (2-[18F]FELP), was selected for further evaluation and in vitro comparison with [18F]FET. Subsequently, 2-[18F]FELP was assessed in vivo and compared with [18F]FET and [18F]FDG in a F98 glioblastoma rat model. 2-[18F]FELP showed improved in vitro characteristics over [18F]FET, especially when the affinity and specificity for system L is concerned. Based on our results, 2-[18F]FELP is a promising new PET tracer for brain tumor imaging.


A short account of forensic dentistry in France.
The earliest records and more recent cases where forensic dentistry has been used to identify bodies in France are described. The establishment of the French Society of Forensic Odontology is detailed.


Transcription, structure, and organoids translate time across the lifespan of humans and great apes.
How the neural structures supporting human cognition developed and arose in evolution is an enduring question of interest. Yet, we still lack appropriate procedures to align ages across primates, and this lacuna has hindered progress in understanding the evolution of biological programs. We generated a dataset of unprecedented size consisting of 573 time points from abrupt and gradual changes in behavior, anatomy, and transcription across human and 8 nonhuman primate species. We included time points from diverse human populations to capture within-species variation in the generation of cross-species age alignments. We also extracted corresponding ages from organoids. The identification of corresponding ages across the lifespan of 8 primate species, including apes (e.g., orangutans, gorillas) and monkeys (i.e., marmosets, macaques), reveals that some biological pathways are extended in humans compared with some nonhuman primates. Notably, the human lifespan is unusually extended relative to studied nonhuman primates demonstrating that very old age is a phase of life in humans that does not map to other studied primate species. More generally, our work prompts a reevaluation in the choice of a model system to understand aging given very old age in humans is a period of life without a clear counterpart in great apes.


Stachydrine promotes angiogenesis by regulating the VEGFR2/MEK/ERK and mitochondrial-mediated apoptosis signaling pathways in human umbilical vein endothelial cells.
Stachydrine is a main active component of Leonurus japonicus (Chinese motherwort), which has traditionally been used to promote postpartum recovery and alleviate myocardial and cerebral ischemic injuries due to its pro-angiogenic effect. Our prior study demonstrated that stachydrine increased angiogenesis in zebrafish embryos, but its pro-angiogenic effect and underlying mechanisms on human umbilical vein endothelial cells (HUVECs) remain largely unknown. In the present study, we further investigated the role of stachydrine in sunitinib-injured HUVECs and its potential molecular mechanisms. The results showed that stachydrine exhibited a protective effect on sunitinib-injured HUVECs and significantly promoted their proliferation, migration, and tube formation, all central events of angiogenesis. In addition, stachydrine inhibited apoptosis and ROS production in sunitinib-injured HUVECs. Furthermore, our findings illustrated for the first time that stachydrine's molecular mechanisms for promoting angiogenesis might correlate with activation of the VEGFR2/MEK/ERK and inhibition of the mitochondrial-mediated apoptosis signaling pathway.


The impact of limb autotomy on mate competition in blue crabs Callinectes sapidus Rathbun.
This study is the first to demonstrate experimentally that autotomy (self-amputation of a body part) adversely affects competition for mates. Experiments were conducted using blue crabs Callinectes sapidus Rathbun to examine the consequences of limb loss and pairing precedence on mate acquisition by males. Two adult males of equivalent size were introduced sequentially into pools containing a sexually-receptive female and observed after 24 h and 48 h. One male in each pair was left intact, while the other experienced: (1) no autotomy, (2) autotomy of one cheliped, or (3) autotomy of both chelipeds, one walking leg, and one swimming leg. In the absence of a competitor (first 24 h), both intact and injured males established precopulatory embraces with females. Intact males were highly successful (84-95%) in defending females from intact or injured intruders in the second 24 h period. Both autotomy treatments, however, significantly reduced the ability of males to defend females from intact intruders. Females in experiments suffered greater frequency of limb loss than did males. In the field, paired blue crabs showed significantly higher incidence of limb loss than unpaired crabs. Limb loss frequency increases with body size, and field observations indicated that larger males may be more successful than smaller males in obtaining females. Both experimental manipulations and field studies provide strong evidence for mate competition in this ecologically and commercially important portunid species.


The detection of stage I ovarian cancer by three-dimensional sonography and power Doppler.
The objective was to determine the diagnostic accuracy of three-dimensional (3D) sonography and 3D power Doppler imaging, used together with standard 2D transvaginal grayscale and color/power Doppler modalities, for preoperative sonographic assessment of suspected ovarian lesions. Five-year retrospective analysis was performed by our experts on ultrasonography and surgery on the reports from 43 referred patients with suspected stage I ovarian cancer. All patients were evaluated during the week prior to surgery at our department. Preoperative sonographic assessment included careful examination of ovarian volume, morphology, and vascularity by four complementary sonographic methods. Scoring systems combining morphological and Doppler parameters were adopted for 2D and 3D sonographic examinations. Final diagnosis was confirmed by a histopathologist. Out of the 43 stage I ovarian cancers, 42 cases were successfully detected preoperatively by four complementary sonographic methods. Only 30 (69.8%) and 37 (86.1%) cases of stage I ovarian cancer were detected by 2D grayscale and combined 2D grayscale and color Doppler sonography, respectively. Morphological analysis obtained by 3D sonography alone detected 32 of 43 ovarian malignancies, reaching a diagnostic rate of 74.4%. Qualitative analysis of tumor vascularity architecture by 3D power Doppler significantly improved the sonographic management process and successfully detected 41 cases of stage I ovarian cancer (95.4%). When morphological features obtained by 3D sonography were added to 3D power Doppler findings, we achieved an even higher diagnostic accuracy of 97.7%. We found a statistically significant difference (P </= 0.01) in diagnostic rates of 3D power Doppler, and especially the combined use of 3D sonography and 3D power Doppler in comparison to those obtained with transvaginal 2D grayscale (P </= 0.002 and P </= 0.001, respectively) or 3D sonography (P </= 0.006 and P </= 0.002, respectively). In comparison to transvaginal 2D grayscale or 3D sonography, 3D power Doppler and especially the combined use of 3D sonography and power Doppler imaging significantly improve diagnostic accuracy in preoperative sonographic assessment of suspected ovarian lesions.


The presence of cadmium in the intertidal environments of a moderately impacted coastal lagoon in western Portugal (Óbidos Lagoon)--spatial and seasonal evaluations.
A seasonal environmental monitoring program was carried out (winter 2009 to summer 2010) to evaluate the spatial and seasonal cadmium concentrations in the intertidal environments of the Óbidos Lagoon (Portugal). Also, some environmental parameters were monitored at each sampling station. Both the water and the sediment samples were contaminated, although to different degrees. In general, cadmium contamination appears to be mostly focused on the inner areas of the lagoon, namely, in Barrosa's arm, which receives a small tributary contaminated by agro-industrial activities. Only cadmium concentration in sediment showed to be significantly influenced by seasons. Some environmental parameters presented spatial and temporal heterogeneity which influenced, to some extent, cadmium bioavailability. The results of this study allow a better understanding of the environmental quality of this ecosystem regarding cadmium contamination and may assist in the definition of future coastal management measures specifically targeted to trace metal contamination and pollution monitoring.


Learning from patient and site perspectives to develop better digital health trials: Recommendations from the Clinical Trials Transformation Initiative.
In order to harness the potential of digital health technologies to enhance the quality of clinical research, it is critical to first understand how to engage patients and research sites when planning and conducting digital health trials. To pave the way for the more effective use of digital health technologies in trials, the Clinical Trials Transformation Initiative has developed the first comprehensive, evidence-based set of recommendations for incorporating patient and site perspectives in digital health trials. While directed primarily at sponsors, these recommendations are expected to be valuable for all stakeholders including investigators.


Floral extract of Tecoma stans: a potent inhibitor of gentamicin-induced nephrotoxicity in vivo.
To highlight the nephroprotective activity of ethyl acetate extract of dried flowers of Tecoma stans for its protective effects on gentamicin-induced nephrotoxicity in albino rats. For studying acute toxicity study, single oral dose of 5,000 mg ethyl acetate floral extract/kg body weight was administered to albino rats (five females, five males). Nephrotoxicity was induced in albino rats by intraperitoneal administration of gentamicin 80 mg/kg/day for eight days. Effect of concurrent administration of ethyl acetate floral extract of Tecoma stans at a dose of 100, 200 and 300 mg/kg/day given by oral route was determined using serum creatinine, serum uric acid, blood urea nitrogen and serum urea as indicators of kidney damage. The study groups contained six rats in each group. As nephrotoxicity of gentamicin is known to involve induction of oxidative stress, in vitro antioxidant activity and free radical-scavenging activity of this extract was also evaluated. For acute toxicity testing both female and male rats administered with the extract at a dose of 5,000 mg/kg. The results showed no toxicity in terms of general behavior change, mortality, or change in gross appearance of internal organs (LD(50) > 5 000 mg/kg). It was observed that the ethyl acetate floral extract of Tecoma stans significantly protected rat kidneys from gentamicin-induced histopathological changes. Gentamicin-induced glomerular congestion, peritubular and blood vessel congestion, epithelial desquamation, accumulation of inflammatory cells and necrosis of the kidney cells were found to be reduced in the groups receiving the ethyl acetate floral extract of Tecoma stans along with gentamicin in a dose dependent manner. The floral extract also reduced the gentamicin-induced increase in serum creatinine, serum uric acid, blood urea nitrogen and serum urea levels (P >0.01). The present study indicates a very important role of reactive oxygen species (ROS) and the relation to renal dysfunction and point to the therapeutic potential of Tecoma stans in gentamicin induced nephrotoxicity.


Catchment source contributions to the sediment-bound organic matter degrading salmonid spawning gravels in a lowland river, southern England.
The ingress of particulate material into freshwater spawning substrates is thought to be contributing to the declining success of salmonids reported over recent years for many rivers. Accordingly, the need for reliable information on the key sources of the sediment problem has progressed up the management agenda. Whilst previous work has focussed on apportioning the sources of minerogenic fine sediment degrading spawning habitats, there remains a need to develop procedures for generating corresponding information for the potentially harmful sediment-bound organic matter that represents an overlooked component of interstitial sediment. A source tracing procedure based on composite signatures combining bulk stable (13)C and (15)N isotope values with organic molecular structures detected using near infrared (NIR) reflectance spectroscopy was therefore used to assess the primary sources of sediment-bound organic matter sampled from artificial spawning redds. Composite signatures were selected using a combination of the Kruskal-Wallis H-test, principal component analysis and GA-driven discriminant function analysis. Interstitial sediment samples were collected using time-integrating basket traps which were inserted at the start of the salmonid spawning season and extracted in conjunction with critical phases of fish development (eyeing, hatch, emergence, late spawning). Over the duration of these four basket extractions, the overall relative frequency-weighted average median (±95% confidence limits) source contributions to the interstitial sediment-bound organic matter were estimated to be in the order: instream decaying vegetation (39±<1%; full range 0-77%); damaged road verges (28±<1%; full range 0-77%); septic tanks (22±<1%; full range 0-50%), and; farm yard manures/slurries (11±<1%; full range 0-61%). The reported procedure provides a promising basis for understanding the key sources of interstitial sediment-bound organic matter and can be applied alongside apportionment for the minerogenic component of fine-grained sediment ingressing the benthos. The findings suggest that human septic waste contributes to the interstitial fines ingressing salmonid spawning habitat in the study area.


Validation of the imperial college surgical assessment device for spinal anesthesia.
Traditionally, technical proficiency for spinal anesthesia has been assessed using observational scales such as global rating scales or task specific checklists. However more objective metrics are required in order to improve novice's training programs. The aim of this study is to validate the hand motion analysis of the Imperial College Surgical Assessment Device (ICSAD) in a simulated model of spinal anesthesia. Three groups of physicians with different levels of experience were video recorded performing a spinal anesthesia in a simulated lumbar puncture torso. Participants' technical performance was assessed with ICSAD, a Global Rating Scale (GRS) and a specific Checklist. Differences between the 3 groups were determined by Kruskal-Wallis test with post hoc Dunn's correction for multiple comparisons. Spearman correlation coefficient between ICSAD variables and the scores of the observational scales were calculated to establish concurrent validity. Thirty subjects participated in the study: ten novice (first year residents), 10 intermediate (third year residents) and 10 experts (attending anesthesiologists). GRS scores were significantly higher in experts, than intermediates and novices. Regarding total path length, number of movements and procedural time measured with ICSAD, all groups had significant differences between them (p = 0.026, p = 0.045 and p = 0.005 respectively). Spearman correlation coefficient was -0,46 (p = 0.012) between total path length measured with ICSAD and GRS scores. This is the first validation study of ICSAD as an assessment tool for spinal anesthesia in a simulated model. Using ICSAD can discriminate proficiency between expert and novices and correlates with previously validated GRS. Its use in the assessment of spinal anesthesia proficiency provides complementary data to existing tools. Our results could be used to design future training programs with reliable goals to accomplish.


Validation of a quantitative FFQ for the Barbados National Cancer Study.
To assess the validity of a 148-item quantitative FFQ (QFFQ) that was developed for the Barbados National Cancer Study (BNCS) to determine dietary intake over 12 months and examine the dietary risk factors. A cross-sectional validation study of the QFFQ against 4 d food diaries. Spearman's rank correlations (ρ), intra-class correlation coefficients (ICC) and weighted κ were computed as measures of concordance, adjusting for daily variations in the food diaries. Cross-classification tables and Bland-Altman plots were created for further assessment. BNCS is a case-control study of environmental risk factors for breast and prostate cancer in a predominantly African-origin population in Barbados. Fifty-four individuals (21 years and older) were recruited among controls in the BNCS who were frequency-matched on sex and age group to breast and prostate cancer cases. Similar mean daily energy intake was derived from the food diary (8201 kJ (1960 kcal)) and QFFQ (7774 kJ (1858 kcal)). Rho for energy and macronutrients ranged from 0·66 (energy) to 0·17 (dietary fibre). The percentage of energy from carbohydrates and protein showed the highest and lowest ICC among macronutrients (0·63 and 0·27, respectively). The highest weighted κ was observed for energy (0·45). When the nutrient intake was divided into quartiles, approximately 34 % of the observations were in the same quartile. This investigation supports the validity of the QFFQ as a method for assessing long-term dietary intake except for dietary fibre, folate, vitamins A, E and B12. The instrument will be a useful tool in the analysis of diet-cancer associations in the BNCS.


Ocular absorption of benzydamine by the rabbit.
An aqueous solution of 0.15 per cent benzydamine hydrochloride, a non-steroidal anti-inflammatory drug, was applied to the rabbit eye. Following topical application to the cornea, the drug was soon detected in the aqueous fluid of the treated eye, whereas the plasma levels were negligible. The possibility that benzydamine can inhibit inflammatory processes in the eye without the risk of side-effects is discussed.


Excessive activation of tyrosine kinases leads to inhibition of proliferation in a thyroid carcinoma cell line.
Autocrine stimulation of growth is a hallmark of many tumor cell lines. In this work we investigated the synthesis and secretion of growth factors and the expression of their corresponding receptors in HTC-TSHr thyroid carcinoma cells. These cells synthesize epidermal growth factor (EGF) receptors and platelet-derived growth factor beta (PDGF beta) receptors and in addition transforming growth factor alpha (TGF alpha), PDGF-A and PDGF-B chains, respectively. Addition of EGF or PDGF-BB to the culture medium resulted in growth inhibition of HTC-TSHr cells. In contrast, treatment of the cells with low concentrations of neutralizing anti-TGF alpha antibodies or tyrosine kinase inhibitors led to stimulation of cell proliferation. Low concentrations of neutralizing anti-PDGF-B antibodies did not affect growth of the cells. As expected, cell proliferation was inhibited when high concentrations of either neutralizing anti-TGF alpha antibodies or anti-PDGF-B antibodies were applied. PDGF-AA did not influence growth of HTC-TSHr cells. We conclude that growth of HTC-TSHr thyroid carcinoma cells is influenced by two autocrine loops between TGF alpha and EGF receptors and between PDGF-B and PDGF beta receptors. However, our data suggest that excessive activation of tyrosine kinase receptors in these cells results in a relative inhibition rather than stimulation of growth.


Prevalence and Auditory Characteristics of Auditory Neuropathy Spectrum Disorder in Adult Population with Sensory Neural Hearing Loss: A Hospital Based Study in South India.
Auditory neuropathy spectrum disorder (ANSD) is a heterogenous group of disorder characterized by abnormalities in auditory brainstem responses (ABR) with preserved otoacoustic emissions and/or cochlear microphonics. The aim of the study is to estimate the prevalence and evaluate the audiological characteristics of ANSD in adult population with sensory neural hearing loss. A prospective study was conducted on the adult population (≥ 18 years) attending ENT outpatients clinic at Rajiv Gandhi Government General Hospital, Chennai. All patients reported to the department with auditory and vestibular symptoms underwent case history, otoscopic examination, and routine audiological evaluation (pure tone audiometry, speech audiometry and immittance audiometry). Patients with indications of ANSD in case history and routine audiological evaluation were further evaluated using distortion product otoacoustic emissions and ABR. A total of 8682 adult population was evaluated during the period of 2017 to 2018. Out of 8682 patients, 1343 (15.46%) of them had sensory neural hearing loss of varying degrees. Out of 1343 adults with sensory neural hearing loss, 24 (1.78%) adults were diagnosed as ANSD. The prevalence of ANSD in adult population with sensory neural hearing loss in our study is 1.32% per 1000 adults. The clinical characteristics of ANSD shows impairment in speech perception irrespective of degree of hearing loss, preserved cochlear functions and abnormal ABR. Hence ANSD is not a rare clinical finding in adults with sensory neural hearing loss, but its prevalence was estimated to be lower in Indian population. Often young females are affected causing significant impairment in speech perception and disability.


Efficacy of ranibizumab combined with photocoagulation for diabetic retinopathy: A meta-analysis study.
Ranibizumab addition may benefit to improve the efficacy in patients with diabetic retinopathy than only photocoagulation, and this meta-analysis aims to explore the impact of ranibizumab addition on efficacy for diabetic retinopathy. PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials assessing the effect of ranibizumab addition on patients with diabetic retinopathy for this meta-analysis. Six randomized controlled trials were finally included in the meta-analysis. Overall, compared with control intervention for diabetic retinopathy, ranibizumab addition showed significantly increased number of neovascularization area reduction (OR = 4.20; 95% CI = 1.47-12.02; P = .007) and reduced fluorescein leakage (MD = -2.53; 95% CI = -3.31 to -1.75; P < .00001), but showed no obvious impact on neovascularization area (MD = -1.80; 95% CI = -3.68 to 0.08; P = .06), photocoagulation retreatment (OR = 1.03; 95% CI = 0.47-2.27; P = .94) or adverse events (OR = 1.45; 95% CI = 0.49-4.29; P = .50). Ranibizumab combined with photocoagulation is effective to improve efficacy for diabetic retinopathy.


SCH 23390, a selective dopamine D1 antagonist, activates dopamine neurons but fails to prevent their inhibition by apomorphine.
SCH 23390, a rather selective D1 receptor blocker, activates the firing rate of dopamine (DA) neurons in the substantia nigra (SN-DA neurons) in rats, similarly to haloperidol (a D1-D2 receptor antagonist) and sulpiride (a selective D2 receptor blocker). These neuroleptics produce no additional increase over the maximal activation produced by SCH 23390. Unlike haloperidol or sulpiride, SCH 23390 fails to prevent the inhibition by apomorphine of SN-DA neurons, a DA autoreceptor-mediated effect. It is suggested that the doses of SCH 23390 that stimulate DA neurons block D2 in addition to D1 receptors, or that D1 blockade results in the functional inactivation of a specific population of D2 receptors as well. The failure of SCH 23390 to block the apomorphine effect indicates that DA autoreceptors can be pharmacologically differentiated form postsynaptic DA receptors.


Advances in our understanding of aging: role of the renin-angiotensin system.
Knowledge about the pathophysiological role of the renin-angiotensin system is constantly improving and its relationship with mechanisms of oxidative stress suggests its possible involvement with the deleterious effects of aging. Recent data opens a new field of investigation in this area.


Chronic ankle instability patients exhibit higher variability in lower extremity joint-coupling variability during drop vertical jumps.
Chronic ankle instability (CAI) has been associated with biomechanical alterations during landing tasks. While joint coupling differences have been reported during gait in patients with CAI, there is no known research assessing joint coupling during a drop-vertical jumping (DVJ). Joint coupling variability measure may provide information on the sensorimotor health of these patients. The purpose of this study was to compare lower extremity joint coupling variability during a DVJ between patients with CAI and controls. Twenty-eight young, active individuals (CAI:n = 14, Control:n = 14) participated in the study. A 3D motion capture system was used to collect kinematics during 15 drop-vertical jump trials. A vector coding analysis was used to assess the variability in the following joint couples: knee sagittal-ankle frontal, knee sagittal-ankle sagittal, hip frontal-ankle frontal, and hip frontal-ankle sagittal. The CAI group had higher joint coupling variability in hip frontal-ankle sagittal, knee sagittal-ankle frontal and knee sagittal-ankle sagittal planes both prior to and following ground contact during the drop vertical jumps. These changes indicate potential adaptations to the constraint of CAI and the task of the DVJ. Higher variability may reflect an attempt by the subjects to explore alternate movement strategies or reflect poor sensorimotor control strategies. Clinicians should consider the challenges of DVJ during rehabilitation as they create a unique task constraint.


Surface analysis of dental amalgams by X-ray photoelectron spectroscopy and X-ray diffraction.
It is important to characterize the surface of dental amalgam in order to understand the process of mercury release from amalgam restorations in the oral cavity. The mercury evaporation occurs not only from the newly made restoration but also from the set material. The surfaces of four different types of amalgams, which had been well set, were analyzed with X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) and the relationship between surface compositions and mercury release was studied. Fresh amalgam surfaces as well as aged surfaces, which were stored for 30 days in air, were investigated using XPS and the chemical states of amalgam components and oxygen were studied. The aged surfaces were also characterized with XRD and grazing angle XRD. With increased oxidation, the surface contents of tin and oxygen were increased in all amalgams. In contrast, the surface contents of copper and mercury were decreased. An increase of zinc or indium content were observed in zinc or indium containing amalgams, respectively. A surface layer enriched with indium and oxygen was clearly detected by XPS but not with grazing angle XRD. The thickness of the enriched surface layer is estimated to be in the order of few nanometer, which is approximately equal to the analysis depth of XPS. In addition, the presence of metallic elements, like tin and zinc, that readily form a stable oxide layer at the surface suppress the release of mercury.


Bilayer characteristics of a diether phosphonolipid analog of the major lung surfactant glycerophospholipid dipalmitoyl phosphatidylcholine.
Thermal and lyotropic phase behavior was studied by X-ray diffraction and differential scanning calorimetry for a diether phosphonolipid analog (DEPN-8) of the major lung surfactant glycerophospholipid dipalmitoyl phosphatidylcholine (DPPC). DEPN-8 differs in an ether, rather than an ester, bond at the acyl chain-backbone linkage and a headgroup phosphonate (isosteric methylene substitution) versus phosphate constituent. Analysis of lamellar diffraction maxima demonstrated that at high relative humidity (98%) and temperatures below the liquid crystal phase transition (approximately 45 degrees C), DEPN-8 formed interdigitated bilayers with a characteristic periodicity of 41.9-46.5 A. At low humidity the gel phase DEPN-8 bilayers were characteristic of a normal L beta phase with a periodicity equivalent to DPPC (57-59 A). Above the liquid crystal thermal phase transition, bilayer spacing for both DEPN-8 and DPPC was 51-52 A, characteristic of the L alpha phase. Complete assessments of both lamellar and in-plane X-ray scattering used to construct electron density profiles and structure-factor plots for DEPN-8 defined more fully the interdigitated bilayer state at high humidity and low temperature. Compared to DPPC, it is energetically favorable for DEPN-8 to form interdigitated bilayers under conditions of excess water and low temperature. The flexible character of the ether bonds in DEPN-8 allows increased hydrophobic interactions between acyl chains, without generating a steric penalty from the increased packing density of the molecules. Additionally, the ether bond and the phosphonate moiety may allow for more energetically favorable interactions between the choline portion of the headgroup and water. The DEPN-8 ether linkage may also contribute to the improved adsorption and film respreading found previously for this phosphonolipid compared to DPPC.


Iatrogenic caecal perforation two days after a caesarean section, a case report.
and importance: The caesarean section is a widely spread procedure and 29.7 million times performed every year inn 169 countries in the world. Overall, complications are seen in 6% for elective caesarean to 15% for emergency caesarean. We here report a case which was initially diagnosed as a postoperative paralytic ileus. After a complicated caesarean section caused by bleeding and problems with haemostasis, a healthy child was born with full mother recovery for the first 24 hours after surgery. Unfortunately, her condition deteriorated between 24 and 48 hours and she reported progressive nausea and painful bloating. Laboratory tests and CT imaging showed progressive signs of inflammation and distention of the caecum and colon. A second CT scan the next day revealed signs of perforation. An ileocecal resection was performed with a primary anastomosis. Full recovery occurred two weeks later. With an estimated incidence of only 0,08%, bowel perforations due to caesarean section, are rare. Moreover, is the clinical presentation diverse and computed topography is essential during the diagnostic process. To avoid potential morbidity and mortality, the surgeon must consider performing a laparotomy in case of a deteriorating patient in non-invasive treatment fails. Caecal perforation must be considered as complication after a caesarean section. An ileocecal resection is necessary in this situation. This case report shows that a primary anastomosis is a possible option in a healthy patient that is hemodynamically stable during the operation. In case of an unhealthy or hemodynamic unstable patient, the safest option is a temporary ileostomy.


In vitro modeling of solid tumor interactions with perfused blood vessels.
Molecular crosstalk between intra-tumor blood vessels and tumor cells plays many critical roles in tumorigenesis and cancer metastasis. However, it has been very difficult to investigate the biochemical mechanisms underlying the overlapping, multifactorial processes that occur at the tumor-vascular interface using conventional murine models alone. Moreover, traditional two-dimensional (2D) culture models used in cancer research do not recapitulate aspects of the 3D tumor microenvironment. In the present study, we introduce a microfluidic model of the solid tumor-vascular interface composed of a human umbilical vein endothelial cell (HUVEC)-lined, perfusable, bioengineered blood vessel and tumor spheroids embedded in an extracellular matrix (ECM). We sought to optimize our model by varying the composition of the tumor spheroids (MDA-MB-231 breast tumor cells + mesenchymal stem cells (MSCs)/human lung fibroblasts (HLFs)/HUVECs) and the extracellular matrix (ECM: collagen, Matrigel, and fibrin gels with or without free HLFs) that we used. Our results indicate that culturing tumor spheroids containing MDA-MB-231 cells + HUVECs in an HLF-laden, fibrin-based ECM within our microfluidic device optimally (1) enhances the sprouting and migration of tumor spheroids, (2) promotes angiogenesis, (3) facilitates vascular invasion, and (4) preserves the structural integrity and functionality of HUVEC-lined microfluidic channels. This model may provide a platform for drug screening and mechanism studies on solid tumor interactions with functional blood vessels.


The use of a novel MUC1 antibody to identify cancer stem cells and circulating MUC1 in mice and patients with pancreatic cancer.
MUC1 is over-expressed and aberrantly glycosylated in >60% of human pancreatic cancer (PC). Development of novel approaches for detection and/or targeting of MUC1 are critically needed and should be able to detect MUC1 on PC cells (including cancer stem cells) and in serum. The sensitivity and specificity of the anti-MUC1 antibody, TAB 004, was determined. CSCs were assessed for MUC1 expression using TAB 004-FITC on in vitro PC cell lines, and on lineage(-) cells from in vivo tumors and human samples. Serum was assessed for shed MUC1 via the TAB 004 EIA. In vitro and in vivo, TAB 004 detected MUC1 on >95% of CSCs. Approximately, 80% of CSCs in patients displayed MUC1 expression as detected by TAB 004. Shed MUC1 was detected serum in mice with HPAF-II (MUC1(high) ) but not BxPC3 tumors (MUC1(low)). The TAB 004 EIA was able to accurately detect stage progression in PC patients. The TAB 004 antibody may be explored as a therapeutic targeting agent for CSCs in PC. The TAB 004 EIA detected circulating MUC1 in a stage-dependent manner in patients with PC and thus may be explored as a PC stage diagnostic biomarker.


IgA nephropathy patients with partial crescent formation benefit from immunosuppressants: evidence from repeat renal biopsy.
Crescent formation is a serious pathological change in the IgA nephropathy (IgAN) which is believed to be primarily mediated by a mixture of parietal epithelial cells, macrophages, and myofibroblasts. It was recommended that IgAN patients with rapid renal hypofunction with a crescent body >50% should begin treatment with corticosteroids combined with cyclophosphamide. However, for patients with partial crescent formation, whether immunosuppressive therapy is necessary is a contested topic. Data from IgAN patients with partial crescent formation who underwent repeat renal biopsy were retrospectively analyzed. From the first to the second renal biopsy, the mean hemoglobin level and albumin level increased significantly (P < 0.05), and uric acid and triglyceride levels decreased significantly (P < 0.05). Also, the 24-hour urinary protein excretion decreased significantly (P < 0.001), but no differences in blood pressure, creatinine level, or estimated glomerular filtration rate. For pathological indices, there were no differences in fluorescence intensity of IgA or C3 deposition (P > 0.05), but the mesangial cell proliferation decreased significantly (P < 0.05), and the proportions of global glomerulosclerosis and tubulointerstitial fibrosis increased significantly (P < 0.05, respectively). In addition, a decreased tendency in the proportion of crescent formation was observed in the second renal biopsy. Immunosuppressive therapy for IgAN patients with partial crescent formation can reduce proteinuria, stabilize renal function, improve anemia, and mitigate acute kidney injury in the short term.


Immunoprofiling bronchoalveolar lavage cells reveals multifaceted smoking-associated immune dysfunction.
Bronchoalveolar lavage (BAL) is an underutilised tool in the search for pulmonary disease biomarkers. While leukocytes with effector and suppressor function play important roles in airway immunity and tumours, it remains unclear if frequencies and phenotypes of BAL leukocytes can be useful parameters in lung cancer studies and clinical trials. We therefore explored the utility of BAL leukocytes as a source of biomarkers interrogating the impact of smoking, a major lung cancer risk determinant, on pulmonary immunity. In this "test case" observational study, BAL samples from 119 donors undergoing lung cancer screening and biopsy procedures were evaluated by conventional and spectral flow cytometry to exemplify the comprehensive immune analyses possible with this biospecimen. Proportions of major leukocyte populations and phenotypic markers levels were found. Multivariate linear rank sum analysis considering age, sex, cancer diagnosis and smoking status was performed. Significantly increased frequencies of myeloid-derived suppressor cells and PD-L1-expressing macrophages were found in current and former smokers compared to never-smokers. While cytotoxic CD8 T-cells and conventional CD4 helper T-cell frequencies were significantly reduced in current and former smokers, expression of immune checkpoints PD-1 and LAG-3 as well as Tregs proportions were increased. Lastly, the cellularity, viability and stability of several immune readouts under cryostorage suggested BAL samples are useful for correlative end-points in clinical trials. Smoking is associated with heightened markers of immune dysfunction, readily assayable in BAL, that may reflect a permissive environment for cancer development and progression in the airway.


Observations bearing upon semi-circular canal dynamics.
It can be shown that following an angular velocity step stimulus delivered in darkness, the nystagmic responses can be effectively 'dumped' after any interval in time by the application of an appropriate step decrement in velocity. In practise the null velocity is bracketed between those step decrements inducing just detectable nystagmus to left and right and can be determined within a range of +/- 1.5 degrees s-1. With test stimuli of 22, 44, and 64 degrees s-1 the 'dump' velocities have been established at varying intervals in time on four normal subjects. Contrary to expectations the dump velocity/time relations for all three test stimuli follow a convergent linear course. The dump velocities are unaffected by fixation suppression of the nystagmus induced by the test stimuli. The seeming irrelevance of nystagmus generation to dump velocity values is confirmed by the good correspondence with the results of a separate study using the oculogyral illusion as a guide in place of nystagmus. These findings are difficult to relate to conventional concepts of cupular dynamics.


Model for end-stage liver disease and organ allocation in liver transplantation: where are we and where should we go?
The Child-Turcotte-Pugh (CTP) score has been used for decades to measure the severity of chronic liver disease. Recent studies have shown that the model for end-stage liver disease (MELD) more accurately predicts the short- and mid-term survival for patients with cirrhosis compared to the CTP system. MELD, which has 3 parameters (serum bilirubin, creatinine, and prothrombin time) that need logarithmic transformation, has the advantage of a wide-range continuous scale and is more objective and less variable. The liver allocation system has changed from a status-based algorithm using the CTP score, to one using a continuous MELD severity score as a reference system to prioritize adult patients on the waiting list since 2002 in the USA. However, there are potential limitations of MELD. An intrinsic defect is that some important parameters, such as hepatic encephalopathy and ascites, which are common adverse complications in cirrhosis, are not included in MELD. It has been suggested to incorporate a low serum sodium level into the prognostic model to enhance the predictive ability. Moreover, the change of MELD over time may provide updated information for patients on the transplant waiting list. In summary, although there was encouraging evidence supporting the prognostic advantage of MELD, the optimal role of MELD in the setting of outcome assessment for cirrhotic patients needs more study. Appropriate modifications and fine tuning of MELD are necessary for determining the ranking status of patients on the waiting list, to avoid a futile transplantation and improve overall patient survival.


Evaluation of acute hematologic and long-term pulmonary toxicities of radioimmunotherapy of Cryptococcus neoformans infection in murine models.
We evaluated acute hematological and long-term pulmonary toxicity of radioimmunotherapy in murine models of Cryptococcus neoformans infection. Activities up to 250 microCi were well tolerated by healthy A/JCr mice for (213)Bi-18B7 and (188)Re-18B7 monoclonal antibodies. In infected mice, doses up to 150 microCi produced only transient toxicity. The lungs of treated mice had no evidence of radiation fibrosis.


Intronic sequences are required for AINTEGUMENTA-LIKE6 expression in Arabidopsis flowers.
The AINTEGUMENTA-LIKE6/PLETHORA3 (AIL6/PLT3) gene of Arabidopsis thaliana is a key regulator of growth and patterning in both shoots and roots. AIL6 encodes an AINTEGUMENTA-LIKE/PLETHORA (AIL/PLT) transcription factor that is expressed in the root stem cell niche, the peripheral region of the shoot apical meristem and young lateral organ primordia. In flowers, AIL6 acts redundantly with AINTEGUMENTA (ANT) to regulate floral organ positioning, growth, identity and patterning. Experiments were undertaken to define the genomic regions required for AIL6 function and expression in flowers. Transgenic plants expressing a copy of the coding region of AIL6 in the context of 7.7 kb of 5' sequence and 919 bp of 3' sequence (AIL6:cAIL6-3') fail to fully complement AIL6 function when assayed in the ant-4 ail6-2 double mutant background. In contrast, a genomic copy of AIL6 with the same amount of 5' and 3' sequence (AIL6:gAIL6-3') can fully complement ant-4 ail6-2. In addition, a genomic copy of AIL6 with 590 bp of 5' sequence and 919 bp of 3' sequence (AIL6m:gAIL6-3') complements ant-4 ail6-2 and contains all regulatory elements needed to confer normal AIL6 expression in inflorescences. Efforts to map cis-regulatory elements reveal that the third intron of AIL6 contains enhancer elements that confer expression in young flowers but in a broader pattern than that of AIL6 mRNA in wild-type flowers. Some AIL6:gAIL6-3' and AIL6m:gAIL6-3' lines confer an over-rescue phenotype in the ant-4 ail6-2 background that is correlated with higher levels of AIL6 mRNA accumulation. The results presented here indicate that AIL6 intronic sequences serve as transcriptional enhancer elements. In addition, the results show that increased expression of AIL6 can partially compensate for loss of ANT function in flowers.