Heart metastases and superior vena cava syndrome.
Superior vena cava syndrome (SVCS) may be due to a tumour infiltrating the right atrium. We present two patients with SVCS. The first one was secondary to solitary atrial metastases of rectal adenocarcinoma and benefited from palliative chemotherapy. The second patient had a disseminated large cell B-cell lymphoma with rapid clinical complete response, but she eventually died after relapse.


[Aspiration biopsy cytology of the diseases of the mammary gland (author's transl)].
A detailed report is given on the results of aspiration cytology used in 612 patients. On the basis of his own experiences he speaks high of cytodiagnostics in the complex of cyto-radio-clinical triplet, where its value may reach 98-100% to the contrary of 60-88% of the other two components. It is rapid, trustful, undangerous, in everyday practice is suggested at every place, where the personal and objective conditions are guaranteed.


Removal of inert COD and trace metals from stabilized landfill leachate by granular activated carbon (GAC) adsorption.
Landfills in Germany are currently approaching stabilization phase; as a result removal of inert organics and potentially toxic elements in the leachate is becoming a primary concern. Dissolved air floatation (DAF) at the secondary stage reduces only 27% of the residual chemical oxygen demand (COD) in the investigated treatment systems; downstream granular activated carbon (GAC) units are required to further reduce COD concentration by 40-56% to meet indirect discharge or direct discharge limits respectively. Therefore, in this study performance in terms of COD and trace metals adsorption of different types of granular activated carbon were compared over different contact times and dosages. GAC 1 with Brunauer-Emmett-Teller (BET) surface area of 719.5 ± 2.1 m2/g and average pore diameter (D) of 4.81 nm was identified to be inappropriate for treatment of leachate from this landfill. GAC 2 (with BET of 1513.7 ± 6.4 m2/g and D of 3.50 nm) was feasible for COD reduction from DAF-pretreated leachate, while GAC 3 (with BET of 644.5 ± 2.6 m2/g and D of 5.65 nm) can be coupled either with biological step alone, or as a tertiary step after the DAF unit. Moreover, as COD is the primary remaining contaminant of interest after secondary and tertiary treatment, spectrometer probes provide a close estimation of COD concentration for use in online monitoring. Beside COD removal, GAC 3 also confirmed the effectiveness of trace metals adsorption even at trace level, as it removed 66, 64, 48, 47, 43, and 25% of copper, cobalt, chromium, manganese, nickel, and zinc, respectively.


The association of idiopathic recurrent early pregnancy loss with polymorphisms in folic acid metabolism-related genes.
The aim of this study was to investigate the association between polymorphisms in folic acid metabolism-related genes and idiopathic recurrent early pregnancy loss (REPL). A prospective case-control study was performed on a cohort of 82 REPL patients and 166 healthy controls. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C was assessed by applying polymerase chain reaction for amplification followed by DNA sequencing, for methionine synthase reductase A66G, solute carrier family 19, member 1 (SLC19A1) G80A and C696T, and genotyping was done by utilizing the Sequenom MassARRAY system. The results revealed a significant association between MTHFR A1298C polymorphism and idiopathic REPL. Haplotype analysis indicated that the MTHFR 677C-MTHFR 1298C allele combination was associated with REPL (P < 0.001). The MTHFR 677C-MTHFR 1298A and SLC19A1 80G-SLC19A1 696C allele combinations had lower frequencies in patients with REPL, but with P > 0.05 (P = 0.093 and P = 0.084, respectively).


Copper(II) binding to alpha-synuclein, the Parkinson's protein.
Variations in tryptophan fluorescence intensities confirm that copper(II) interacts with alpha-synuclein, a protein implicated in Parkinson's disease. Trp4 fluorescence decay kinetics measured for the F4W protein show that Cu(II) binds tightly (Kd 100 nM) near the N-terminus at pH 7. Work on a F4W/H50S mutant indicates that a histidine imidazole is not a ligand in this high-affinity site.


Subacute sclerosing panencephalitis and chronic viral encephalitis.
Subacute sclerosing panencephalitis (SSPE) is a chronic infection of the central nervous system associated with the presence of mutant measles virus in the brain. It presents as a progressive, usually fatal disease. The diagnosis is based on clinical criteria and an elevated titer of measles antibodies in the cerebrospinal fluid (CSF). Electroencephalography and imaging studies provide supportive laboratory data. A brain biopsy is indicated only when CSF serology is negative or equivocal in a suspected case to assess the presence of inclusion bodies, measles virus antigens, or viral RNA. Among many drugs and methods tried in the treatment, the highest rate of stabilization or improvement was obtained with intraventricular human lymphoblastoid interferon-α and oral inosiplex. Further research for more available and efficient therapeutic regimens is warranted. Measles and SSPE are preventable by maintenance of high rates of immunization in the population.


Mycobacterium bovis BCG vertebral osteomyelitis after intravesical BCG therapy, diagnosed by PCR-based genomic deletion analysis.
We report a case of Mycobacterium bovis BCG vertebral osteomyelitis 1.8 years after intravesical BCG therapy for bladder cancer. We differentiated BCG from other Mycobacterium tuberculosis complex members by PCR analysis of deletion regions and started an appropriate chemotherapy regimen resulting in the remission of symptoms within 1 month.


MiR-128b is down-regulated in gastric cancer and negatively regulates tumour cell viability by targeting PDK1/Akt/NF-κB axis.
Gastric cancer (GC) is the fourth most prevalent type of cancer worldwide, which is usually caused by the interaction between environmental and genetic factors, or epigenetic aspects. Referring to the non-coding RNAs, miR-128b has been reported to be associated with many tumour cases, and exerts distinct functions in different types of cancers. However, the function of miR-128b in GC onset and progression largely remains unknown. In the present study, we found that miR-128b expression was down-regulated in tissues from 18 GC patients and 3 carcinoma cell lines. In turn, over-expression of miR-128b suppressed GC cell proliferation, invasion and promoted apoptosis. Moreover, miR-128b was predicted to bind the 3'UTR of PDK1 gene using bioinformatic target-screening tools. Accordingly, ectopic expression of miR-128b inhibited the PDK1 expression at both transcriptional and post-transcriptional levels, and furthermore, the expression of gene tailed by the 3'UTR of PDK1 gene was significantly decreased in a dualluciferase reporter assay, suggesting that PDK1 was a direct target of miR-128b in GC cells. In the conditon of miR- 128b over-expression, we also observed spontaneous inactivation of the Akt/NF-κB signalling, implying PDK1 was a potential regulator of this pathway. In conclusion, our study shed some novel light on miR-128b-PDK1/Akt/NF-κB axis on GC progression.


Limbal epithelial crypt: a model for corneal epithelial maintenance and novel limbal regional variations.
To determine the distribution of cell membrane proteins and extracellular matrix proteins around the limbal epithelial crypt (LEC) compared with adjacent limbus and corneal epithelium. Serial histological sections of human corneoscleral limbus rims were stained with antibodies of interest by standard immunohistochemistry. Superficial cells of the limbus were desmoglein 3 positive, compared with the negative basal cells of the limbus that correspond to cells with more stemlike properties. The LEC had a much lower proportion of desmoglein 3 staining in comparison. Tenascin C staining demonstrated regional variations of the limbus depending on their association with the LEC. Limbus that was associated with or adjacent to the LEC had a greater tenascin C expression compared with normal limbus, whereas the LEC demonstrated the greatest tenascin C expression. Based on these and similar results previously reported for connexin 43, we propose a novel model on the mechanism of corneal surface epithelium maintenance involving 3 different limbal regions: zone 1, limbus including the LEC; zone 2, limbus associated with the LEC; and zone 3, limbus distant to the LEC. The noted limbal variations may influence the selection of the donor site for limbal grafts in the future.


[Hospitalization in Turin for measles and related complications 1973-1983: medical and economic evaluation in relation to the opportunity for vaccination intervention].
Admission for measles and related complications in three hospitals of the city of Turin (Italy), during the period 1973-1983, have been examined. The aim of our research was to evaluate the frequency of admission, the more affected age class, the rate of hospital acquired infections, the mean cost of admission. 1790 admissions were observed during 11 years (1507 for measles and 283 for measles complications), for a total of 15092 days of stay. The age class less than 3 was found to be the more affected by measles complications, while the rate of nosocomial infections was 3.5%.


Exploring routine hospital antenatal care consultations - An ethnographic study.
Listening to women as part of their antenatal care has been recognized as valuable in understanding the woman's needs. Conversations as part of routine antenatal interactions offer ideal opportunities for women to express themselves and for midwives to learn about the woman's issues and concerns. The antenatal visit and the convention of antenatal consultations for midwives have not been well explored or defined and much of what takes place replicate medical consultative processes. As a consequence, there is little to assist midwives construct woman-centred care consultations for their routine antenatal care practice. This study showed how some practices were better in promoting the woman's voice and woman-centred care in the hospital setting. Contemporary focused ethnography using both interview and observations, explored how midwives from six different public antenatal clinics in South Australia organized their antenatal care consultations with pregnant women. Thematic analysis of the data provided insights into professional interpretation of woman-centred practice. How midwives interacted with women during routine antenatal care events demonstrated that some practices in a hospital setting could either support or undermine a woman-centred philosophy. Individual midwives adopted practices according to their own perceptions of actions and behaviors that were considered to be in accordance with the philosophy of woman-centred care. Information arising from this study has shown ways midwives may arrange antenatal care consultations to maximize women's participation.


[New therapeutic strategies for the different subtypes of urticaria].
Urticaria is one of the most common skin diseases. It is divided into several categories including acute and chronic urticaria as well as physical urticaria and special subtypes such as cholinergic and autoimmune urticaria. The causes of urticaria are multiple. In more than 80%, urticaria is triggered by an inflammatory focus, a subclinical infection or autoimmune actions. In addition, non-specific pharmacological or toxin-mediated release of inflammatory mediators from basophils or mast cells can also trigger urticaria. These new aspects in the pathophysiology of urticaria suggest new and promising therapeutic strategies. The first line treatment of urticaria still consists of non-sedating H1-antihistamines. Since urticaria has a profound impact on quality of life, effective treatment is very important. We consider new therapeutic options based on our long-term experience in treating patients with urticaria.


Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model.
Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0-450 kPa (0-800 Pa∙s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146-220 kPa and 221-290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0-145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85-145 kPa.


Implementing the modular MHC model for predicting peptide binding.
The challenge of predicting which peptide sequences bind to which major histocompatibility complex (MHC) molecules has been met with various computational techniques. Scoring matrices, hidden Markov models, and artificial neural networks are examples of algorithms that have been successful in MHC-peptide-binding prediction. Because these algorithms are based on a limited amount of experimental peptide-binding data, prediction is only possible for a small fraction of the thousands of known MHC proteins. In the primary field of application for such algorithms--vaccine design--the ability to make predictions for the most frequent MHC alleles may be sufficient. However, emerging applications of leukemia-specific T cells require a patient-specific MHC-peptide-binding prediction. The modular model of MHC presented here is an attempt to maximize the number of predictable MHC alleles, based on a limited pool of experimentally determined peptide-binding data.


The "Hard Problem of Consciousness" Arises from Human Psychology.
Consciousness presents a "hard problem" to scholars. At stake is how the physical body gives rise to subjective experience. Why consciousness is "hard", however, is uncertain. One possibility is that the challenge arises from ontology-because consciousness is a special property/substance that is irreducible to the physical. Here, I show how the "hard problem" emerges from two intuitive biases that lie deep within human psychology: Essentialism and Dualism. To determine whether a subjective experience is transformative, people judge whether the experience pertains to one's essence, and per Essentialism, one's essence lies within one's body. Psychological states that seem embodied (e.g., "color vision" ∼ eyes) can thus give rise to transformative experience. Per intuitive Dualism, however, the mind is distinct from the body, and epistemic states (knowledge and beliefs) seem particularly ethereal. It follows that conscious perception (e.g., "seeing color") ought to seem more transformative than conscious knowledge (e.g., knowledge of how color vision works). Critically, the transformation arises precisely because the conscious perceptual experience seems readily embodied (rather than distinct from the physical body, as the ontological account suggests). In line with this proposal, five experiments show that, in laypeople's view (a) experience is transformative only when it seems anchored in the human body; (b) gaining a transformative experience effects a bodily change; and (c) the magnitude of the transformation correlates with both (i) the perceived embodiment of that experience, and (ii) with Dualist intuitions, generally. These results cannot solve the ontological question of whether consciousness is distinct from the physical. But they do suggest that the roots of the "hard problem" are partly psychological.


Functional integrity of the T-tubular system in cardiomyocytes depends on p21-activated kinase 1.
p21-activated kinase (Pak1), a serine-threonine protein kinase, regulates cytoskeletal dynamics and cell motility. Recent experiments further demonstrate that loss of Pak1 results in exaggerated hypertrophic growth in response to pathophysiological stimuli. Calcium (Ca) signaling plays an important role in the regulation of transcription factors involved in hypertrophic remodeling. Here we aimed to determine the role of Pak1 in cardiac excitation-contraction coupling (ECC). Ca transients were recorded in isolated, ventricular myocytes (VMs) from WT and Pak1(-/-) mice. Pak1(-/-) Ca transients had a decreased amplitude, prolonged rise time and delayed recovery time. Di-8-ANNEPS staining revealed a decreased T-tubular density in Pak1(-/-) VMs that coincided with decreased cell capacitance and increased dis-synchrony of Ca induced Ca release (CICR) at individual release units. These changes were not observed in atrial myocytes of Pak1(-/-) mice where the T-tubular system is only sparsely developed. Experiments in cultured rabbit VMs supported a role of Pak1 in the maintenance of the T-tubular structure. T-tubular density in rabbit VMs significantly decreased within 24h of culture. This was accompanied by a decrease of the Ca transient amplitude and a prolongation of its rise time. However, overexpression of constitutively active Pak1 in VMs attenuated the structural remodeling as well as changes in ECC. The results provide significant support for a prominent role of Pak1 activity not only in the functional regulation of ECC but for the structural maintenance of the T-tubular system whose remodeling is an integral feature of hypertrophic remodeling.


Resistance of salmonellae isolated in 1962 to chloretetracycline.
Among 652 salmonellae examined, Salmonella typhimurium displayed a much higher incidence of resistance to chlortetracycline than did other serotypes. Among S. typhimurium cultures from man, the incidence of resistance (38%) increased markedly over that of cultures isolated 3 years previously (13.9%), whereas a similar increase was not noted among cultures from fowls. Resistance among cultures from animals other than fowls (72.5%) was due largely to the high incidence of resistance among cultures from bovine sources (93.7%).


Sniff and mimic - Intranasal oxytocin increases facial mimicry in a sample of men.
The neuropeptide oxytocin (OT) has many potential social benefits. For example, intranasal administration of OT appears to trigger caregiving behavior and to improve the recognition of emotional facial expressions. But the mechanism for these effects is not yet clear. Recent findings relating OT to action imitation and to the visual processing of the eye region of faces point to mimicry as a mechanism through which OT improves processing of emotional expression. To test the hypothesis that increased levels of OT in the brain enhance facial mimicry, 60 healthy male participants were administered, in a double-blind between-subjects design, 24 international units (IUs) of OT or placebo (PLA) through nasal spray. Facial mimicry and emotion judgments were recorded in response to movie clips depicting changing facial expressions. As expected, facial mimicry was increased in the OT group, but effects were strongest for angry infant faces. These findings provide further evidence for the importance of OT in social cognitive skills, and suggest that facial mimicry mediates the effects of OT on improved emotion recognition.


Whether modern cell technologies can break down biological limitations of tissue-specific regeneration of the myocardium.
The paper reviews modern concepts of physiological and reparative regeneration of the myocardium as a highly specific and highly differentiated tissue system. Special attention was given to evaluation of the proliferative potential of cardiomyocytes, in particular, to the existence of a population of resident cardiac stem cells in the myocardium. Modern approaches to replenishment of massive cardiomyocyte loss via transplantation and transdifferentiation of adult and embryonic stem cells are discussed and the possibilities of using cell technologies for induction of tissue-specific regeneration of the myocardium are analyzed.


Electrochemotherapy in non-melanoma head and neck skin cancers: a three-center experience and review of the literature.
The main purposes of this study were to evaluate the efficacy of electrochemotherapy in head and neck tumors, to assess local tumor control, its safety profile and its impact on the patients' quality of life. This is a multicenter prospective, non-randomized phase II trial. This trial was carried out at the Dermatology Clinic of the "Sapienza" University of Rome, at the Dermatology Clinic of the University of Chieti and at the Dermatology Clinic of the University of Turin. Fifty-five patients with head and neck cancer were recruited. Electrochemotherapy was carried out according to the ESOPE guidelines. Statistical analyses were performed using Stata/SE v.12.0 Statistical Software. A significant clinical response was achieved in 50/55 patients with 91% of objective response rate (OR). Thirty-three out of 55 patients showed a complete response (CR) (60%); 17 treated patients had a partial response (PR) (31%). A significantly higher CR rate was obtained in patients not previously treated by surgery (15/19; 79%), with respect to those with a previous excision of the tumor (14/30; 47%) (P=0.025). An additional parameter influencing response is represented by anesthesia: patients treated by ECT with general anesthesia were characterized by significantly higher CR rate (68%) than those treated with local anesthesia (27%) (P=0.014). Our experience confirmed high efficiency in local tumor control, excellent toxicity profile, tissue preservation with good cosmetic and functional results, even with repeated applications. ECT can represent a first-line treatment in the local management of head and neck cancers.


Are There Ethnic Inequalities in Revascularisation Procedure Rate after an ST-Elevation Myocardial Infarction?
Previously, ethnic inequalities in prognosis after a first acute myocardial infarction were observed in the Netherlands. This might be due to differences in revascularisation rate between ethnic minority groups and ethnic Dutch. Therefore, we investigated inequalities in revascularisation rate after occurrence of an ST-elevation myocardial infarction (STEMI) between first generation ethnic minority groups (henceforth, migrants) and ethnic Dutch. All STEMI events between 2006 and 2011 were identified in a subset of the Achmea Health Database, which records medical care to persons insured at the Achmea health insurance company, a major health insurance company in the central part of the Netherlands. Ethnic Dutch and migrants from Suriname (Hindustani Surinamese and non-Hindustani Surinamese), Morocco, and Turkey were included (n = 1,765). Multivariable Cox proportional hazards regression analyses were used to identify ethnic inequalities in revascularisation rate (percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG)) after a STEMI event. On average, 73.2% of STEMI events were followed by a revascularisation procedure. After adjustment for confounders (age, sex, degree of urbanization) no significant differences in revascularisation rate were found between the ethnic Dutch population and Hindustani Surinamese (HR: 1.04; 0.85-1.27), non-Hindustani Surinamese (HR: 0.98; 0.63-1.51), Moroccan (HR: 0.94; 0.77-1.14), and Turkish migrants (HR: 1.04; 0.88-1.24). Additional adjustment for comorbidity and neighborhood income did not change our findings. Our study suggests no ethnic inequalities in revascularisation rate after a STEMI event. This finding is in agreement with the universally accessible health care system in the Netherlands.


The flow-volume loop in tetraplegics.
We have studied the FVC and maximum flow-volume loop in 20 tetraplegics and the results have been compared with the predicted normal values. The FVC in sitting position is reduced at approximately half the normal predicted values and is significantly lower than in supine and Trendelenburg. At high lung volumes the flows are reduced at half the normal values. At low lung volumes the reduction is smaller (71.5 per cent).


Aqueous chlorination of ephedrine: Kinetic, reaction mechanism and toxicity assessment.
Ephedrine (EPH) is widely detected in the water environment, because it is the major ingredient in drugs treating influenza, asthma or hypotension, and is also a highly sought-after chemical precursor in the illicit manufacture of methamphetamine. In this study, transformation of EPH during the chlorination process was investigated for the first time, and the impact of water parameters including pH, different cations and anions on EPH transformation was evaluated as well. The degradation of EPH in the presence of NaClO fit the second order reaction kinetics, with a rate constant of 7.43 × 102 ((mol·L-1)-1·min-1). Increasing the dosage of NaClO increased the observed pseudo first order rate constant for EPH degradation (kobs). Degradation rate of EPH decreased with the increasing pH from 2.0 to 10.0, due to the formation of a chlorammonium intermediate that reacted with NaClO. Low concentration of Br- and I- did not exert significant influence on the degradation of EPH, while at high concentrations a promotive effect was observed. Other ions including Fe3+, Cu2+, NO3-, SO42-, Mg2+ and Ca2+ exerted negative effects even at relatively low concentrations. Based on the degradation products/intermediates identified by UPLC-MS/MS, the EPH degradation pathways were proposed. The reaction mechanism involved in the EPH degradation included dehydration, hydroxylation, deamination and demethylation. Toxicity assays by V. qinghaiensis sp. nov proved that the EPH transformation products were much more toxic than the parent compound. Results indicated that chlorination is an effective approach for the elimination of EPH in the aquatic environment, however, attention should be paid to its toxicity involvement during the chlorination process.


Long-lived reactive species formed on proteins induce changes in protein and lipid turnover.
Proteins are major targets for oxidative damage in vivo due to their high abundance and rapid rates of reaction with both one-electron (radical) and two-electron oxidants (e.g. singlet oxygen, hypochlorous acid, peroxynitrous acid, reactive aldehydes). The turnover of both native and modified proteins is critical for maintenance of cell homeostasis, with this occurring via multiple pathways including proteasomes (for cytosolic species), the Lon protease (in mitochondria), and the endo-lysosomal systems (both extra- and intra-cellular species). Evidence has been presented for both enhanced and diminished rates of catabolism of modified proteins, as well as altered turnover of native (unmodified) proteins as a result of damage to these systems, potentially as a result of the accumulation of damaged proteins. In recent studies we have shown that long-lived reactive species forms on proteins (hydroperoxides, chloramines and aldehydes) can modify the activity of proteasomal and lysosomal enzymes. Some of the above species are efficient inhibitors of the tryptic and chymotryptic activities of the 26S proteasome, as well as lysosomal cathepsin and acid lipase activities. These are key species in the turnover of both proteins and lipoproteins. The loss of enzyme activity is accompanied in many cases, by oxidation of critical thiol residues via molecular reactions. For reactive aldehydes (either free or protein-bound) direct enzyme inhibition can occur as well as modulation of protein levels and, in the case of lysosomes, changes in lysosomal numbers. Overall, these data indicate that the formation of reactive species on proteins can modulate cell function by multiple pathways including interference with the turnover of native proteins (including critical cell signalling molecules) and alterations in the rate of clearance of modified proteins. Both pathways may contribute to the development of a number of human pathologies associated with oxidative damage.


Operative management of choanal atresia: a 15-year experience.
To analyze factors affecting 15-year surgical outcomes of choanal atresia repair. Case series. Tertiary care pediatric hospital. Between April 17, 1996, and March 23, 2010, a total of 42 patients aged 3 days to 15 years underwent endoscopic or transpalatal choanal atresia repair by our pediatric otolaryngology faculty. Reoperation and restenosis rates, with consideration of effects of mitomycin C therapy, stenting, and postoperative dilation. Three of 42 patients were excluded because of inadequate follow-up data; the follow-up time for the remaining 39 patients averaged 6.3 years (range, 1-14.9 years). Excluding 6 patients whose initial repair was performed by other physicians, 31 of 33 patients in whom we performed initial repair had a total of 43 endoscopic surgical procedures (19 patients had unilateral procedures, and 12 patients had bilateral procedures), and the other 2 underwent bilateral transpalatal repair. Of the total 43 sides we operated on endoscopically, 9 sides (21%) required revision surgery, including excision of scar tissue or additional drilling of persistent bony stenosis. No significant difference was observed in the rate of restenosis among cases treated endoscopically with mitomycin C (22 of 43 operative sides, P = .13), with stenting (36 of 43 operative sides, P = .99), or with subsequent dilation (P = .45). When we used stents, they were usually (in 28 of 36 patients) left in place for 15 days or longer. Our revision rate after initial endoscopic repair of choanal atresia was low and was unaffected by adjuvant mitomycin C therapy or stenting.


Randomized controlled study of plasma exchange combined with molecular adsorbent re-circulating system for the treatment of liver failure complicated with hepatic encephalopathy.
To evaluate the use of plasma exchange (PE) combined with the molecular adsorbent re-circulating system (MARS) for the treatment of liver failure complicated with hepatic encephalopathy. A prospective randomized controlled study was conducted to compare the therapeutic effect of MARS treatment (MARS group, n=60) with that of PE combined with MARS treatment (PE+MARS group, n=60) in patients with liver failure complicated with hepatic encephalopathy. The serum total bilirubin and blood ammonia levels were significantly decreased compared with pretreatment levels after 3 days of both the MARS treatment (p=0.0001, p<0.001) and PE+MARS treatment (both p<0.0001) and the Glasgow coma scale score was significantly increased (both p<0.0001). The 30-day mortality rate was 10.0% (6/60) in the MARS group and 11.7% (7/60) in the PE + MARS group. The per capita cost of treatment was significantly lower in the PE + MARS group than in the MARS group (p=0.0003). Both MARS and PE + MARS therapy can safely and effectively be used to treat liver failure complicated with hepatic encephalopathy, but PE + MARS therapy reduces serum total bilirubin level more effectively and is more cost-effective.


Topical misoprostol therapy for plasma cell vulvitis: a case series.
To present the first reported case series of plasma cell vulvitis successfully treated with topical misoprostol. Three women with vulvar pain and lesions secondary to plasma cell vulvitis refractory to conventional therapy were treated with topical misoprostol compounded in white petrolatum. All three patients had resolution of pain and lesions within 6 weeks of starting topical misoprostol. All patients tolerated the 0.01% concentration; however, local side effects were seen with the higher 0.02% concentration. Plasma cell vulvitis is a rare and painful vulvar disorder that is often refractory to therapy. All three patients in this case series were successfully treated with topical misoprostol. The immunosuppressive effects of misoprostol are hypothesized to be the mechanisms of action of this novel therapy for plasma cell vulvitis.


Cognitive Impairment in Idiopathic Normal Pressure Hydrocephalus.
Idiopathic normal pressure hydrocephalus (iNPH) is a significant cause of the severe cognitive decline in the elderly population. There is no cure for iNPH, but cognitive symptoms can be partially alleviated through cerebrospinal fluid (CSF) diversion. In the early stages of iNPH, cognitive deficits occur primarily in the executive functions and working memory supported by frontostriatal circuits. As the disease progresses, cognition declines continuously and globally, leading to poor quality of life and daily functioning. In this review, we present recent advances in understanding the neurobiological mechanisms of cognitive impairment in iNPH, focusing on (1) abnormal CSF dynamics, (2) dysfunction of frontostriatal and entorhinal-hippocampal circuits and the default mode network, (3) abnormal neuromodulation, and (4) the presence of amyloid-β and tau pathologies.


[The relief of the mineralization front of the natural surfaces and characteristics of the structure of the lacunar-canalicular system in the human mandible osseous tissue].
Using the material from 12 corpses of males aged 19-44 years, the structural elements of mandibular osseous tissue were studied with scanning electron microscopy. The mosaic pattern was established in different areas which characterized the functional activity of particular region. In the bone surface, the resorbing, forming and formed (or inactive) areas were detected. Nutrition of the osseous tissue is provided by the lacunar-canalicular system, which is characterized by permanent remodelling of the bed. The development of osteocytic lacunae included the sequential formation of their bottom, walls and roof. These findings should be considered during preparation, conservation and selection of plastic material; they could also serve as a basis for theoretical and practical substantiation of the methods for optimization of reparative osteogenesis in the development of the new ways of directed influence on the processes of bone formation and resorption.


Ratios of Food Amounts across Three Portion Size Categories on a Food Frequency Questionnaire in Men and Women.
For some quantitative food frequency questionnaire (QFFQ) items, data may be insufficient to set gram weights for multiple portion size (PS) categories. Ratios of food amounts across PS categories may be used to quantify these PS for less frequently consumed food items. To explore the ratios of food amounts reported in 24-hour dietary recalls (24HDRs) by a sample of participants in a cohort study who chose the A (smallest) or C (largest) PS category on the QFFQ, relative to the food amounts for those who chose the B PS category. This study was conducted as a cross-sectional design. Data were from participants (n=2,360) who completed three 24HDRs and the QFFQ in a calibration study of the Multiethnic Cohort Study in 1994-1997. Median food amounts were calculated from 24HDRs for participants who selected each PS category (A, smallest; B; and C, largest) of items on the QFFQ. A-to-B and C-to-B ratios were computed if reported by five or more people in the 24HDRs: A-to-B ratios for 68 items (men) and 88 items (women); C-to-B ratios for 93 items (men) and 79 items (women). The t test was used to compare the mean A-to-B ratios and C-to-B ratios as preset on the QFFQ with those from the 24HDRs and to examine sex differences. Analysis of variance was used to compare the mean ratios among race and ethnicity groups. Mean A-to-B and C-to-B ratios were 0.71±0.15 and 1.45±0.35 in men and 0.71±0.15 and 1.44±0.40 in women based on the 24HDRs. Compared with the original QFFQ PS (A-to-B ratio=0.5±0.07; C-to-B ratio=1.8±0.30), the ratios were closer to 1 both in men and women (P<0.001). There were no significant sex differences or racial or ethnic differences. These results provide guidance on appropriate ratios to use to set values for small and large PS categories on a QFFQ, particularly for items with insufficient information on usual PS.


Use of atropine in patients with recent myocardial infarction during exercise myocardial perfusion study. Use of atropine during exercise myocardial perfusion SPECT.
Patients with recent myocardial infarction frequently require a myocardial perfusion study for risk stratification. However a conclusive study cannot be accomplished in many due to non-attainment of target heart rate. To evaluate the effect of pre-stress administration of atropine in exercise performance of patients with recent myocardial infarction. Study included 43 test and 43 control patients and were matched for their age, sex, status of pretest exercise tolerance, area of infarction and for interval between infarction and stress thallium test. Atropine (0.01 mg/kg) was administered intravenously 3 min prior to treadmill stress in all the 43 test patients and no atropine was administered to control patients. Target heart rate was attained in 95.3% patients receiving atropine compared to in 67.4% of control patients. There was no significant difference between mean ages (p>0.33), basal BP (p>0.47), peak BP (p>0.18) of both groups. There was significant difference between the increment in exercise-induced heart rate (p<0.004), peak heart rate (p<0.001) and double product (p<0.001) attained between both groups. No significant adverse effect was noted in patients who received atropine. Pre-stress administration of atropine in patients with recent myocardial infarction is safe and results in a significantly better exercise performance, which might be useful in decreasing the number of equivocal myocardial perfusion studies.


Degradation of epidermal growth factor receptors by cathepsin L-like protease: inhibition of the degradation by c-Ha-ras gene products.
Extract of NIH3T3 mouse fibroblasts contains a protease which can cleave epidermal growth factor receptor (EGF receptor). This protease was tentatively named cathepsin X and purified to near homogeneity. The characteristics of cathepsin X were similar to those of cathepsin L and the proteolytic activity of cathepsin X was inhibited by c-Ha-ras gene products.


Longitudinal follow-up reveals occurrence of successive Cryptosporidium bovis and Cryptosporidium ryanae infections by different subtype families in dairy cattle.
Cryptosporidium bovis and Cryptosporidium ryanae are common species causing cryptosporidiosis in cattle. Data accumulated thus far indicate that the infection patterns of the two species could be different between areas with and without Cryptosporidium parvum. To better understand the infection dynamics of these two species, cross-sectional and longitudinal studies of Cryptosporidium spp. were conducted using genotyping and subtyping tools. In the cross-sectional survey, analysis of 634 faecal samples from two farms identified only C. bovis and C. ryanae in pre-weaned calves. Two birth cohorts of 61 and 78 calves were followed longitudinally over a 12 month period, which revealed the shedding of C. bovis oocysts started at 1-2 weeks of age and peaked initially at 6-8 weeks of age. Altogether calves experienced four infections by six subtype families of C. bovis, with each infection caused by different subtype families. In contrast, the shedding of C. ryanae oocysts started at 2-4 weeks of age, and the two infections were caused by different subtype families. The cumulative incidence of C. bovis infection was 100% (58/58, 32/32) on both farms, compared with 84.4-98.3% (27/32 and 57/58) for C. ryanae infection. Overall, the mean duration of oocyst shedding in the cohort studies was 3.8-4.0 weeks for C. bovis compared with 2.1 weeks for C. ryanae. The oocyst shedding intensity was high (mean oocysts per gram of faeces was over 105) during the first infection with each species but became significantly lower in the later infections. Cryptosporidium ryanae was associated with the occurrence of diarrhea on one farm, while C. bovis was not. The data indicate that there is an early occurrence of C. bovis and C. ryanae in pre-weaned calves with high infection intensity in the absence of C. parvum. Calves infected with the same Cryptosporidium sp. multiple times could be associated with the presence of subtype-specific immunity.


A voice for traumatized women: inclusion and mutual support.
This paper reports experiences related to including women in recovery and peer support, in a project that developed integrated services for women with co-occurring mental health and substance use disabilities who have also survived violence. We describe strategies to include women in recovery and a unique peer-run group, which integrates trauma, mental health, and substance abuse recovery. Both research and perspectives of women in recovery are used to discuss the emerging themes of mutuality, bonding, and a focus on strengths.


Analysis of inactive X chromosome structure by in situ nick translation.
Nick translation assays of fixed interphase female fibroblasts with tritiated nucleotides demonstrated a characteristic absence of label over sex chromatin. The chromatin bodies were nearly always peripheral in location and a ribbon of nick translatable DNA was detected between the sex chromatin and the nuclear envelope. High voltage electron microscopy indicated the possibility of a special nuclear envelope attachment region. The apparent resistance of sex chromatin to nick translation did not appear to be due to resistance to DNase I attack.


The prognostic value of C-reactive protein and albumin in patients undergoing resection of colorectal liver metastases. A retrospective cohort study.
The systemic inflammation-based Glasgow Prognostic Score (GPS) and modified GPS (mGPS), as measured by preoperative C-reactive protein (CRP) and albumin, correlate with poor survival in several cancers. This study evaluates the prognostic value of these scores in patients with colorectal liver metastases (CRLM). This retrospective study assessed the prognostic role of preoperatively measured GPS and mGPS in patients undergoing liver resection because of CRLM. Clinicopathological data were retrieved from local databases. The prognostic value of GPS and mGPS were compared and a Cox regression model was used to find independent predictors of overall survival. In total, 849 consecutive patients between January 2005 and December 2015 were included. Patients with GPS 0 had a median survival of 70 months compared to 49 months in patients with GPS 1, and 27 months in patients with GPS 2. Multivariable analyses showed that GPS 1 (HR = 1.51, 95%CI [1.14-2.01]) and GPS 2 (HR = 2.78, 95%CI [1.79-4.31]), after correction for age >70 years (HR = 1.75 [1.36-2.26]), and extended resection (HR = 2.53, 95%CI[1.79-3.58]), were associated with poor overall survival. A preoperative GPS is an independent prognostic factor in patients with CRLM, and appears to be a better prognostic tool than mGPS.


Specific evaluation of localized bone mass and bone loss in the rat using dual-energy X-ray absorptiometry subregional analysis.
Dual-energy X-ray absorptiometry (DXA), together with the use of ultra-high resolution software, recently appeared as an accurate method for determining bone mineral density (BMD) in the rat. In order to assess the ability of this technique to detect changes in bone mass in the rat rapidly and precisely, we measured BMD at various sites of the femur using DXA subregional analysis. In particular, we studied the BMD of the metaphyseal part of the femur (M-BMD) rich in trabecular bone, and compared the values obtained with the cancellous bone volume measured by histomorphometry. In short-term ovariectomized animals (experiment 1), M-BMD was the only parameter to differentiate statistically between 10 ovariectomized (OVX) and 10 SHAM-operated (SHAM) rats (-11.2%, p < 0.01) 9 days after surgery. M-BMD still expressed the greatest variation between OVX and SHAM rats 42 days following ovariectomy (experiment 2) (-16.1%, p < 0.001 v -6.2%, p < 0.01 for the total femur BMD) and confirmed previous data demonstrating a greater loss of cancellous than cortical bone after cessation of ovarian activity. M-BMD was highly correlated with cancellous bone volume (BV) in normal (r = 0.82, p < 0.001, n = 30), OVX (r = 0.77, p < 0.001, n = 22) and SHAM (r = 0.88, p < 0.001, n = 21) rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Facilitating factors for colorectal cancer screening.
In this retrospective study, we examined factors that facilitated receipt of colorectal cancer (CRC) screening in a sample of low-income, predominantly African Americans participating in a tailored telephone education intervention. A total of 61 individuals who received CRC screening were matched on age and sex with 61 individuals who had not received screening. Using records collected as part of the intervention, we identified facilitating factors and compared them between groups. We identified 8 facilitating factors, of which there were significant bivariate relationships with 6 factors. These 6 factors were stated familiarity with CRC test, seemed to only need reminder calls, seemed ready to screen, primary care physician (PCP) encouraged CRC screening, had an upcoming PCP appointment, and being prevention oriented. Identifying facilitating factors in those who receive screening may lead to insights about what factors need to be cultivated in those who do not receive screening.


Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.
Tyrosine-kinase inhibitor (TKI) therapy for human cancers is not curative, and relapse occurs owing to the continued presence of tumor cells, referred to as minimal residual disease (MRD). The survival of MRD stem or progenitor cells in the absence of oncogenic kinase signaling, a phenomenon referred to as intrinsic resistance, depends on diverse growth factors. Here we report that oncogenic kinase and growth-factor signaling converge to induce the expression of the signaling proteins FBJ osteosarcoma oncogene (c-FOS, encoded by Fos) and dual-specificity phosphatase 1 (DUSP1). Genetic deletion of Fos and Dusp1 suppressed tumor growth in a BCR-ABL fusion protein kinase-induced mouse model of chronic myeloid leukemia (CML). Pharmacological inhibition of c-FOS, DUSP1 and BCR-ABL eradicated MRD in multiple in vivo models, as well as in mice xenotransplanted with patient-derived primary CML cells. Growth-factor signaling also conferred TKI resistance and induced FOS and DUSP1 expression in tumor cells modeling other types of kinase-driven leukemias. Our data demonstrate that c-FOS and DUSP1 expression levels determine the threshold of TKI efficacy, such that growth-factor-induced expression of c-FOS and DUSP1 confers intrinsic resistance to TKI therapy in a wide-ranging set of leukemias, and might represent a unifying Achilles' heel of kinase-driven cancers.


Identification, mapping and cloning of the thymidine kinase gene of fish lymphocystis disease virus.
The thymidine kinase (TK) gene of fish lymphocystis disease virus (FLDV) was identified by biochemical transformation of 3T3 TK negative (TK-) to 3T3 TK positive (TK+) cells using specific viral DNA sequences. DNA fragments of the viral genome used in this study were obtained from a defined gene library of FLDV genome containing the complete viral DNA sequences. The selection of the converted cells was carried out under the condition of the HAT selection procedure. The results of these experiments revealed that the EcoRI FLDV DNA fragment C (11.2 kbp; 0.611 to 0.718 map units) is able to transform 3T3 TK- to 3T3 TK+ cells. Additional experiments using the subclones of EcoRI DNA fragment C revealed that DNA sequences of 4.1 kbp size between the coordinates 0.669 to 0.718 of the FLDV genome possessed the ability for biochemical transformation, indicating that the TK gene locus is located in this particular region.


Differences between reversible (self-association) and irreversible aggregation of rHuG-CSF in carbohydrate and polyol formulations.
Severe immunogenic and other debilitating human disorders potentially induced by protein aggregates have brought this phenomenon into the focus of biopharmaceutical science over the past decade. Depending on its driving forces, the process induced in the model protein rHuG-CSF may be either reversible or irreversible, resulting in the assembly of self-associated protein species or irreversible aggregates of various final morphologies. The aim of our work was to investigate the correlation between irreversible and reversible aggregation and the protective effect of non-specific formulation stabilisers, selected from the group of carbohydrates and polyols including trehalose, xylitol, cellobiitol, turanose, cellobiose, leucrose, lactitol, lyxose, and sorbitol, against both irreversible protein aggregation and reversible self-association processes of the rHuG-CSF. The formation of irreversible aggregates was thermally induced and evaluated using differential scanning calorimetry and size-exclusion chromatography. As opposed to the irreversible aggregation process, the process of self-association was induced by the agitation experiment by directly augmenting the protein solution contact surfaces. Absence of statistical connectivity between different stabilisers' ability to inhibit self-association or aggregation reactions indicates that these are two distinct physicochemical processes with different formulation stabilizing outcomes. Reaction mechanism of thermally induced aggregation observed in the study was in line with published literature data, while the reaction mechanism for self-association process was postulated. The postulate has been verified experimentally by isothermal calorimetry and agitation set of experiments conducted after size-exclusion chromatography and asymmetrical flow field-flow fractionation separation of monomeric, dimeric, trimeric, oligomeric, and large self-associated forms detected on multi-angle light scattering, fluorescence, UV, and refractive index detectors. Besides defining the mechanism and kinetic of self-association in stabilized rHuG-CSF formulations, special attention was also paid to the shifts and ranks of the free energy of the aggregation or self-association transition states.


GABA released from cultured cortical neurons influences the modulation of t-[(35)S]butylbicyclophosphorothionate binding at the GABAA receptor Effects of thymol.
Thymol is a monoterpene that specifically interacts with synaptic neural functions in neuronal GABA-operated Cl(-) channels. Here we explore the effects of thymol, and propofol as positive control, on t-[(35)S]butylbicyclophosphorothionate ([(35)S]TBPS) binding in primary cultures of cortical neurons. The study includes a meaningful analysis of the effect of various exposure buffers, and their correlation with GABA released from cells, chloride influx through the GABA(A) receptor and GABA transporter activity. Cell viability was also determined. Thymol and propofol inhibited the binding of [(35)S]TBPS to cells exposed to Tris-citrate-NaCl buffer whereas a biphasic effect was observed in HEPES solution. The different effects of the two buffers analysed are due to the higher capacity of Tris-citrate-NaCl buffer to induce the release of endogenous GABA facilitating the binding of [(35)S]TBPS to its recognition site at the GABA(A) receptor. Released GABA in the presence of this buffer was inhibited by the neuronal GABA transporter inhibitor SKF 100330-A. Tris-citrate-NaCl buffer also induced a chloride influx, which was reverted by picrotoxinin. TBPS binding in living cells is facilitated by GABA released from the cells, which in turn activates basal GABA(A) receptor activity. The results deepen on the allosteric mechanism of thymol as positive modulator of the GABA(A) receptor. Furthermore, we corroborate [(35)S]TBPS binding as an important test to verify the capacity of drugs to act on and recognize a site at the GABA(A) receptor.


Visual, cognitive, and neurodevelopmental outcome at 51/2 years in children with perinatal haemorrhagic-ischaemic brain lesions.
To determine predictive values of early visual and neurocognitive assessment in children with perinatally acquired haemorrhagic or ischaemic brain lesions selected on the basis of ultrasound, 63 children (37 boys, 26 girls), who had been followed and examined until the age of 18 months, were reexamined at 5 1/2 years. Good correlations between visual and neurodevelopmental assessments at 18 months and at 5 1/2 years were found. When ultrasound abnormalities were combined with early visual and neurocognitive assessment data, good predictive values, especially for the group of children who had grade 2 to 4 leukomalacia, were found for visual acuity and neurodevelopment.


Antipsychotic medication use in association with quantitative heel ultrasound (QUS).
Antipsychotic medication use has been associated with decreased bone mineral density; however, less is known whether antipsychotics affect other parameters of bone health. Therefore, the aim of this study was to investigate the association between antipsychotic medication use and quantitative heel ultrasound (QUS) in a population based sample of men and women. Thirty-one antipsychotic users and 155 non-users matched for age and sex were drawn from the Geelong Osteoporosis Study. QUS was undertaken and included the parameters: Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI). Current medication use, lifestyle factors, anthropometry and socio-economic status were collected. Generalized Estimation Equation models were conducted to determine associations between antipsychotic medication use and each of the QUS parameters, adjusting for covariates. Antipsychotic users were less active, consumed less alcohol, were more likely to smoke and take antidepressants; otherwise, the groups were similar. After adjusting for age, sex and weight, antipsychotic users had a 7.7 % lower mean BUA [108.70 (95 % CI 104.26-113.14) vs. 116.42 (95 % CI 115.48-117.37) dB/MHz, p = 0.005] and 7.4 % lower mean SI [89.92 (95 % CI 86.89-92.95) vs. 97.30 (95 % CI 96.48-98.12) %, p < 0.001] compared to non-users. Differences in mean SOS between antipsychotic users and non-users failed to reach statistical significance (p = 0.07). Antipsychotic use was associated with lower QUS parameters. The risk of bone deterioration should be considered when antipsychotics are prescribed.


Structure and dynamics of lipid monolayers: implications for enzyme catalysed lipolysis.
We have investigated the role of the substrate on the interfacial activation of lipases by an interdisciplinary study of the structure and dynamics of 1,2-sn dipalmitoylglycerol monolayers at distinct surface pressures. The diglyceride Langmuir film undergoes two phase transitions occurring at 38.3 and 39.8 A2 per molecule. The first transition is unique for diglyceride molecules and is driven by a reorganization of the headgroups causing a change in the hydrophobicity of the oil-water interface. X-ray diffraction studies of different mesophases shows that in the two highest pressure phases, the alkyl chains pack in an hexagonal structure relaxing to a distorted-hexagonal lattice in the lowest pressure phase with the alkyl chains tilted by approximately 14 degrees in a direction close to a nearest neighbour direction.


Intellectual status of working-class children adopted early into upper-middle-class families.
Failure rates observed (13 +/- 6 percent for school failures, 17 +/- 5 percent for scores below 95 on a collective IQ test) were far below those expected from the social class of birth (55 percent, 51 percent) or observed in a control group (56 +/- 8 percent, 49 +/- 9 percent) but close to those expected from the social class of adoption (15 percent, 15 percent).


Informed consent in shoulder surgery.
Informed consent is an essential tool for diagnosis and therapy in medicine, and is of fundamental importance in surgery, where it underpins the operation itself. Its origins can be traced back to US forensic medicine but is now incorporated into the Italian legal system, with different consequences depending on the context in which it is applied. This article describes our experiences in shoulder surgery, with suitable references to legislation and analysis of the literature studies in this area.


[Use of electrodiagnosis and electrostimulation in the combined treatment of children with anal sphincter incompetence].
Results of the examination and treatment of 23 children with the incompetent sphincter ani were analyzed. The method of electrical excitation is recommended for exact determination of the degree of disturbance of the sphincter function. These data were used for the selection of methods of treatment. The application of electrostimulation in the pre- and post-operative period facilitated more rapid restoration of the obturator system of the rectum and sometimes allowed avoiding surgical interventions.


Iodine deficiency in pregnant women residing in an area with adequate iodine intake.
To prevent iodine deficiency disorders, the World Health Organization, United Nations Children's Fund, and International Council for the Control of Iodine Deficiency Disorders established that for a given population median urinary iodine concentrations (UIC) must be 100-199 microg/L in clinically healthy subjects and 150-249 microg/L in clinically healthy pregnant women. We evaluated whether in the urban area of Rome, Italy, where a salt iodination program (30 mg/kg) was introduced since 2005, an increased demand of iodine during pregnancy is guaranteed. During 2006, 51 pregnant women at first trimester of a physiologic gestation were consecutively enrolled on presentation to evaluate UIC in morning spot urine samples. As controls, 100 age-matched clinically healthy non-pregnant women were evaluated. The median UICs were 182 microg/L (range 85-340 microg/L) and 74 microg/L (range 17-243 microg/L), respectively, in the control and pregnant groups. This difference was highly significant (P < 0.001). In particular, the UIC was found to be lower than adequate in 4% of control women compared with 92% of pregnant women. This difference of occurrences was highly significant (P < 0.001). This observational study demonstrated that, despite the adequate supplementation of iodine intake, most pregnant women appear not to be protected against iodine deficiency. If confirmed in larger case studies, this finding claims the attention of relevant professionals to monitor iodine nutrition during gestation, assuming that ordinary supplementation of iodine intake seems to be sufficient only in non-gestational conditions.


Antigenic properties of some equine influenza viruses.
The antigenic relationships between the haemagglutinins of five A/equine-1 viruses and between six A/equine-2 viruses were examined using post-infection ferret and immunized pony sera. Similar results were obtained with sera from both species for the A/equine-1 viruses and these confirmed minor antigenic differences between the prototype A/Prague 1/56 virus and viruses isolated in England in 1973 and 1977. Considerable antigenic differences were found between five of the A/equine-2 viruses, using ferret sera, but these differences were less evident using pony sera. The response of ponies to the inactivated viruses indicated that there was little need to change the virus strains used in the manufacture of commercial equine influenza vaccines.


Correlation functions in isotropic and anisotropic turbulence: the role of the symmetry group.
The theory of fully developed turbulence is usually considered in an idealized homogeneous and isotropic state. Real turbulent flows exhibit the effects of anisotropic forcing. The analysis of correlation functions and structure functions in isotropic and anisotropic situations is facilitated and made rational when performed in terms of the irreducible representations of the relevant symmetry group which is the group of all rotations SO(3). In this paper we first consider the needed general theory, and explain why we expect different (universal) scaling exponents in the different sectors of the symmetry group. We exemplify the theory context of isotropic turbulence (for third order tensorial structure functions) and in weakly anisotropic turbulence (for the second order structure function). The utility of the resulting expressions for the analysis of experimental data is demonstrated in the context of high Reynolds number measurements of turbulence in the atmosphere.


α-Klotho released from HK-2 cells inhibits osteogenic differentiation of renal interstitial fibroblasts by inactivating the Wnt-β-catenin pathway.
Randall's plaques (RP) are well established as precursor lesions of idiopathic calcium oxalate (CaOx) stones, and the process of biomineralization driven by osteogenic-like cells has been highlighted in RP formation, but the mechanism is poorly understood. Given the inhibitory role of α-Klotho (KL), an aging suppressor protein with high expression in kidneys, in ectopic calcification and the close association between KL gene polymorphisms and urolithiasis susceptibility, we determined the potential role of KL in RP formation. This study found that both soluble KL (s-KL) and transmembrane KL (m-KL) were downregulated, and that s-KL but not m-KL was inversely correlated with upregulation of osteogenic markers in RP tissues. Additionally, s-KL expression was markedly suppressed in human renal interstitial fibroblasts (hRIFs) and slightly suppressed in HK-2 cells after osteogenic induction, intriguingly, which was echoed to the greater osteogenic capability of hRIFs than HK-2 cells. Further investigations showed the inhibitory effect of s-KL on hRIF osteogenic differentiation in vitro and in vivo. Moreover, coculture with recombinant human KL (r-KL) or HK-2 cells suppressed osteogenic differentiation of hRIFs, and this effect was abolished by coculture with KL-silenced HK-2 cells or the β-catenin agonist SKL2001. Mechanistically, s-KL inactivated the Wnt-β-catenin pathway by directly binding to Wnt2 and upregulating SFRP1. Further investigations identified activation of the Wnt-β-catenin pathway and downregulation of SFRP1 and DKK1 in RP tissues. In summary, this study identified s-KL deficiency as a pathological feature of RP and revealed that s-KL released from HK-2 cells inhibited osteogenic differentiation of hRIFs by inactivating the Wnt-β-catenin pathway, not only providing in-depth insight into the role of s-KL in renal interstitial biomineralization but also shedding new light on the interaction of renal tubular epithelial cells with interstitial cells to clarify RP formation.


Cerebral venous sinus thrombosis in an adolescent with Ewing sarcoma.
Although thromboembolic complications are common in adult patients with malignant diseases, cerebral venous sinus thrombosis has been rarely described in cancer afflicted pediatric and adolescent population. A 16-year-old adolescent girl referred for complaints of pain and swelling on her left leg. On physical examination, a solid tibial mass was discovered. After the diagnosis of Ewing sarcoma with a tru-cut biopsy, chemotherapy protocol consisting of cisplatin, ifosfamide, adriamycine, and vincristine was started. During the first course of the treatment, the patient expressed headache, diplopia, and ptosis. Contrast-enhanced magnetic resonance (MR) images and MR angiography showed superior sagittal and transverse sinus thromboses. After anticoagulant therapy, the thromboses disappeared within 1.5 months. She received her chemotherapy protocol with the anticoagulant prophylaxis. After a follow-up period of 12 months, she is still in a good neurological recovery without any sequel. Children and adolescents with cancer should be monitored closely for thrombotic complications. We discuss this uncommon case to draw attention to the importance of early diagnosis and adequate treatment of intracranial thrombosis in childhood cancer, and we review the relevant literature.


Field-scale differences in rhizosphere micro-characteristics of Cichorium intybus, Ixeris polycephala, sunflower, and Sedum alfredii in the phytoremediation of Cd-contaminated soil.
Understanding the intricate interplay between Cd accumulation in plants and their rhizosphere micro-characteristics is important for the selection of plant species with profitable Cd phytoextraction and soil remediation efficiencies. This study investigated the differences in rhizosphere micro-ecological characteristics and Cd accumulation in chicory, Ixeris polycephala, sunflower, and Sedum alfredii in low-moderate Cd-contaminated soil. Data reveal that the dominant organic acids in rhizosphere soil that responded to Cd were oxalic and lactic acids in chicory and Ixeris polycephala, tartaric acid in sunflower, and succinic acid in Sedum alfredii. These unique organic acids could also influence the abundance of specific rhizobacterial communities in rhizosphere soil that were Sphingomonadaceae and Bradyrhizobiaceae in both Sedum alfredii (9.75 % and 2.56 %, respectively) and chicory (8.98 % and 2.82 %, respectively) rhizosphere soil, Xanthomonadaceae in both Sedum alfredii and Ixeris polycephala rhizosphere soil, and Gaiellaceae in chicory rhizosphere soil. In this case, the combined effects of the organic acids and unique rhizobacterial communities by plant species increased the bioavailable concentration of Cd in Sedum alfredii, Ixeris polycephala, and sunflower rhizosphere soil, while decreasing the Cd-DOM concentrations in chicory rhizosphere soil and the water-extractable Cd reduced by 88.02 % compared to the control. Though the capacity for Cd accumulation in the shoots of chicory was weaker than of Sedum alfredii but better than either Ixeris polycephala or sunflower, chicory presented better Cd translocation and harbored Cd mainly as the low toxic chemical form of pectates and proteins-bound Cd and Cd oxalate in its shoot. Generally, chicory, as an economic plant, is suitable for phytoremediation of low-moderate Cd-contaminated soil after Sedum alfredii.


Iontophoretically applied microtubule inhibitors induce transganglionic degenerative atrophy of primary central nociceptive terminals and abolish chronic autochtonous pain.
Transcutaneous iontophoresis of microtubule inhibitors (Vinblastin, Vincristin, Formyl-Leurosin) in rats induces depletion of fluoride-resistant acid phosphatase (FRAP) and transganglionic degenerative atrophy (trggl. deg. atr.) of the central terminals of primary nociceptive neurons, probably via blockade of axoplasmic transport in the peripheral sensory nerves. Radiochemical experiments prove that about 0.2% of the microtubule inhibitors applied iontophoretically at the skin reach the level of nociceptive axon terminals. 40 out of 48 patients suffering from chronic intractable pain of diverse etiology (postherpetic, paresthetic, ischaemic and trigeminal neuralgia, alcoholic and diabetic polyneuropathy, meralgia, brachialgia, discopathia, arthropathia and terminal pain) were successfully treated with Vinblastin or Vincristin iontophoresis. Iontophoretically applied microtubule inhibitors do not affect the blood cell count, have no side-effects and do not impair the skin at the site of application.


Document recommendation based on interests of co-authors for brain science.
Personalized knowledge recommendation is an effective measure to provide individual information services in the field of brain science. It is essential that a complete understanding of authors' interests and accurate recommendation are carried out to achieve this goal. In this paper, a collaborative recommendation method based on co-authorship is proposed to make. In our approach, analysis of collaborators' interests and the calculation of collaborative value are used for recommendations. Finally, the experiments using real documents associated with brain science are given and provide supports for collaborative document recommendation in the field of brain science.


[65-year old female patient with persistent hypercalcemia].
A 65-year old patient presented with newly diagnosed hypercalcemia and elevated parathyroid hormone levels. Exploration of parathyroid glands was performed under the diagnosis of primary hyperparathyroidism and was combined with thyreoidectomy due to concomittant multinodular goiter. However, no parathyroid adenoma was identified despite careful exploration. Therefore, the operation was terminated and an ectopic adenoma was suspected. A (99m)Tc-sestamibi scintigraphy with SPECT, neck ultrasound, neck CT scan with contrast media and selective venous sampling were performed for further localization of the adenoma. A single adenoma localized in the submandibular area of the left jaw was suspected and confirmed during surgical reexploration. Postoperatively, parathyroid hormone levels were below detection level and the patient required short-term calcium supplementation for symptomatic hypocalcemia.


Management of the acute knee dislocation: the Pittsburgh experience.
Traumatic dislocation of the knee is among the most severe form of ligament injury to the lower extremity. While the incidence of knee dislocations is low, this injury is associated with a high rate of complications including amputation. There is potential for a traumatic knee dislocation to present to the emergency department after spontaneous or in-field reduction. This requires a vigilant, comprehensive, and systematic approach to the injured knee and extremity to avoid limb-threatening oversights. At the University of Pittsburgh a comprehensive algorithm has been developed to facilitate accurate and efficient diagnosis and treatment of complex traumatic knee injuries. The following manuscript includes a detailed review of the literature and explains our specific approach to this diagnostic dilemma.


Three-dimensional human neural culture on a chip recapitulating neuroinflammation and neurodegeneration.
Neuroinflammation has either beneficial or detrimental effects, depending on risk factors and neuron-glia interactions in neurological disorders. However, studying neuroinflammation has been challenging due to the complexity of cell-cell interactions and lack of physio-pathologically relevant neuroinflammatory models. Here, we describe our three-dimensional microfluidic multicellular human neural culture model, referred to as a 'brain-on-a-chip' (BoC). This elucidates neuron-glia interactions in a controlled manner and recapitulates pathological signatures of the major neurological disorders: dementia, brain tumor and brain edema. This platform includes a chemotaxis module offering a week-long, stable chemo-gradient compared with the few hours in other chemotaxis models. Additionally, compared with conventional brain models cultured with mixed phenotypes of microglia, our BoC can separate the disease-associated microglia out of heterogeneous population and allow selective neuro-glial engagement in three dimensions. This provides benefits of interpreting the neuro-glia interactions while revealing that the prominent activation of innate immune cells is the risk factor leading to synaptic impairment and neuronal loss, validated in our BoC models of disorders. This protocol describes how to fabricate and implement our human BoC, manipulate in real time and perform end-point analyses. It takes 2 d to set up the device and cell preparations, 1-9 weeks to develop brain models under disease conditions and 2-3 d to carry out analyses. This protocol requires at least 1 month training for researchers with basic molecular biology techniques. Taken together, our human BoCs serve as reliable and valuable platforms to investigate pathological mechanisms involving neuroinflammation and to assess therapeutic strategies modulating neuroinflammation in neurological disorders.


Differential hydroxylation efficiency of the two non-heme carotene hydroxylases: DcBCH1, rather than DcBCH2, plays a major role in carrot taproot.
Carotene hydroxylase plays an important role in catalyzing the hydroxylation of carotene to xanthopylls, including two types: non-heme carotene hydroxylase (BCH type) and heme-containing cytochrome P450 hydroxylase (P450 type). Two BCH-encoding genes were annotated in the carrot genome. However, the role of BCHs and whether there are functional interactions between the duplicated BCHs in carrot remains unclear. In this study, two BCH encoding genes, DcBCH1 and DcBCH2, were cloned from carrot. The relative expression level of DcBCH1 was much higher than that of DcBCH2 in carrot taproots with different carotene accumulation levels. Overexpression of DcBCH1 in 'KRD' (high carotene accumulated) carrot changed the taproot color from orange to yellow, accompanied by substantial reductions in α-carotene and β-carotene. There was no obvious change in taproot color between transgenic 'KRD' carrot overexpressing DcBCH2 and control carrot. Simultaneously, the content of α-carotene in the taproot of DcBCH2-overexpressing carrot decreased, but the content of β-carotene did not change significantly in comparison with control carrot. Using the CRISPR/Cas9 system to knock out DcBCH1 in 'KRD' carrot lightened the taproot color from orange to pink-orange; the content of α-carotene in the taproot increased slightly, while the β-carotene content was still significantly decreased, compared with control carrot. In DcBCH1-knockout carrot, the transcript level of DcBCH2 was significantly increased. These results indicated that in carrot taproot, DcBCH1 played the main function of BCH enzyme, which could hydroxylate α-carotene and β-carotene; DcBCH1 and DcBCH2 had functional redundancy, and these two DcBCHs could partially compensate for each other.


Synthetic nucleosides and nucleotides. 43. Inhibition of vertebrate telomerases by carbocyclic oxetanocin g (C.OXT-G) triphosphate analogues and influence of C.OXT-G treatment on telomere length in human HL60 cells.
Telomerase, responsible for telomere synthesis, is expressed in approximately 90% of human tumor cells but seldom in normal somatic cells. In this study, inhibition by carbocyclic oxetanocin G triphosphate (C. OXT-GTP) and its analogues was investigated in order to clarify the susceptibility of telomerase to various nucleotide analogues. C. OXT-GTP competitively inhibited telomerase activity with respect to dGTP However, C. OXT-GTP had a potent inhibitory effect on DNA polymerase alpha. It was examined whether the nucleoside (C. OXT-G) was able to alter telomere length in cultured human HL60 cells. Contrary to expectation, long-term treatment with 10 microM C. OXT-G was found to cause telomere lengthening.


Percutaneous arterial closure in peripheral vascular disease: a prospective randomized evaluation of the Perclose device.
Patients with peripheral vascular disease have been excluded from initial studies of percutaneous suture-mediated closure devices (SMCD) despite representing a significant proportion of those requiring endovascular intervention. We sought to determine whether these devices could be safely used in patients with peripheral vascular disease. Patients were stratified into two groups and five subgroups on the basis of indication for arteriography, and they were prospectively randomized at the end of the procedure to receive either the SMCD or manual compression. Ankle-brachial index was determined and duplex ultrasound scanning of the accessed femoral artery was performed, before and after the procedure. Ultrasound data included peak systolic velocity, minimum intraluminal vessel diameter, and presence or absence of calcified plaque. Time to hemostasis, ambulation, and discharge were recorded, and major or minor complications were noted. Of 102 patients included in the study, 52 patients were randomized to receive the SMCD. There was no difference in ankle-brachial index, minimum intraluminal vessel diameter, or peak systolic velocity in the accessed vessel after closure with SMCD or manual compression. Time to hemostasis, ambulation, and discharge was significantly less in the SMCD group (P =.001). Presence of calcified plaque was not associated with complications (P =.146). In the SMCD group, hemostasis was achieved with 49 of 52 devices (94.2%). There were six complications (5.9%), two of which were major and required operative intervention. All complications were hemorrhagic and not occlusive. There was no difference in overall complication rate between SMCD (7.7%) and manual compression (4.0%) groups (P =.678). No infection was noted in any of the 102 patients. Suture-mediated percutaneous arterial closure can be safely performed in patients with peripheral vascular disease, even in the presence of calcified plaque. This closure technique enables shorter time to hemostasis, ambulation, and hospital discharge. There are observed differences in minor, but not major, complication rates for MC versus percutaneous arterial closure in patients with peripheral vascular disease, but these differences did not achieve statistical significance in this small series.


Single, remote-magnetic catheter approach for pulmonary vein isolation in patients with paroxysmal and non-paroxysmal atrial fibrillation.
The aim of the study was to investigate the safety and efficacy of a single, remote-magnetic catheter navigation system (MNS) for pulmonary vein isolation (PVI). A total of 107 PVI procedures in 71 patients with paroxysmal (32%), persistent (38%) and longstanding-persistent (30%) atrial fibrillation (AF) were analyzed. A wide area circumferential radiofrequency ablation PVI was performed with either an 8mm MNS (first 35 procedures) or an irrigated MNS (last 36 procedures) catheter. Electrical isolation was confirmed with circular pacing/sensing using the MNS catheter and a coronary sinus catheter. Our follow-up strategy in the first year and upon symptoms thereafter was: clinical check plus 12-lead ECG (100%) and 24 h-ECG recordings (76%) at 3 month intervals, trans-telephonic ECG (79%) twice daily and upon symptoms (4 weeks every 3 months), or ECG monitoring via implanted devices (9%). The mean procedure time at 1st PVI was 247±61 min, and mean fluoroscopy time was 44±18 min. The overall complication rate was 2%. Success rates did not differ at the 1st PVI regarding catheter type (p=0.931) but were dependent on history of AF: patients with paroxysmal AF had the highest success rates of 58% and 29% after 1 and 3 years of follow-up, respectively (p=0.0084). PVI with a single MNS catheter is safe and is associated with short fluoroscopy exposition. Despite a rigorous follow-up strategy success rates favorably compare with recently published data on hand-held PVI. Thus, multipolar catheters or a 2nd trans-septal puncture may not be mandatory.


Variance of DDAH/PRMT/ADMA pathway in atrial fibrillation dogs.
Atrial fibrillation (AF) may cause thrombus formation in the left atrial appendage (LAA). Thrombus formation is associated with LAA endocardial dysfunction. Because asymmetrical dimethylarginine (ADMA) can cause endothelial dysfunction by decreasing nitric oxide (NO) formation, we investigated plasma ADMA and nitrite/nitrate (NO(X)) levels and myocardial dimethylarginine dimethylaminohydrolase-2 (DDAH-2), protein arginine methyltransferase-1 (PRMT-1), and endothelial NO synthase (eNOS) protein contents from AF dogs. The results displayed that plasma ADMA level significantly increased, and plasma NO(X) concentration significantly decreased. Compared with normal heart, DDAH-2 expression was unchanged in the fibrillating atria. However, the DDAH activity was significantly decreased in the fibrillating atria. PRMT-1 expression significantly increased in the LAA and in the left atrium (LA). ENOS expression significantly decreased in the LA. ENOS and PRMT-1 expressions were unchanged in the right atria. Our results suggested that the DDAH-PRMT-ADMA system maybe play a pivotal role in regulating endothelial function in AF.


Deep neck abscesses: the Singapore experience.
This study aims to review our experience with deep neck abscesses, identify key trends, and improve the management of this condition. This is a retrospective chart review of patients diagnosed with deep neck abscesses in the Department of ENT (Otorhinolaryngology) at Tan Tock Seng Hospital, Singapore between 2004 and 2009. Patient demographics, etiology, bacteriology, systemic disease, radiology, treatment, complications, duration of hospitalization, and outcomes were reviewed. 131 patients were included (64.9% male, 35.1% female) with a median age of 51.0 years. 54 (41.2%) patients had diabetes mellitus. The parapharyngeal space (23.7%) was the most commonly involved space. Odontogenic and upper airway infections were the leading causes of deep neck abscesses (28.0% each). Klebsiella pneumoniae (27.1%) was the most commonly cultured organism in this study and among the diabetic patients (50.0%). 108 (82.4%) patients underwent surgical drainage. 42 patients suffered complications. All 19 patients, who had upper airway obstruction, had either a tracheostomy or intubation. Patients with multi-space abscesses, diabetes mellitus, and complications had prolonged hospitalizations. Old age and diabetes are risk factors for developing deep neck abscesses and their sequelae. The empiric choice of antibiotics should recognize that a dental source is likely, and that Klebsiella is most common in diabetics. Surgical drainage and adequate antibiotic coverage remains the cornerstone of treatment of deep neck abscesses. Therapeutic needle aspiration may successfully replace surgical drainage, if the abscesses are small and no complications are imminent. Airway obstruction should be anticipated in multi-space and floor of mouth abscesses.


Effect of ethanolic extract from Morus alba L. leaves on the quality and sensory aspects of chilled pork under retail conditions.
The aim of this study was to investigate the performance of ethanolic extract from Morus alba L. leaves (MLEE) in preserving chilled pork under retail conditions. The four treatments were 5 mg/mL sodium benzoate solution (SB), 1 mg/mL MLEE solution (high-concentration MLEE; HM), 0.5 mg/mL MLEE solution (low-concentration MLEE; LM), and 0 mg/mL MLEE solution (C). The quality characteristics, pH, thiobarbituric acid reactive substances values, metmyoglobin, total volatile basic nitrogen, and number of microbes of MLEE-treated chilled pork stored at 4 °C for 9 days were consistent with those obtained by the SB treatment and lower than those obtained by the C treatment. Sensory analyses showed that treatment of pork with MLEE did not have a negative impact on its sensory characteristics. MLEE can extend the shelf life of chilled pork from 3 days to 6 days (9 days) in first-class (second-class) fresh meat. Results suggest that MLEE could be a candidate resource in the preservation of chilled pork.


Limitations of the lipid state hypothesis for atherosclerosis are revealed by X-ray diffraction measurements.
The lipid state hypothesis proposes that liquid crystalline states of cholesteryl esters play a role in the development and persistence of the fatty streak lesions characteristic of atherosclerosis. We have tested several corollaries suggested by this hypothesis and find that the ensemble of droplets in atherosclerotic tissue are predominantly in the isotropic (fluid) state at 37.0 degrees C. Furthermore, the liquid-crystalline state transition behavior of these droplets is not influenced significantly by the distribution of component cholesteryl ester species. There are no significant correlations between the transition behavior of the droplets and the age, sex, or race of the subjects from which tissue samples were taken. These results show that the lipid state hypothesis is weak, and that the origin and persistence of fatty streak lesions in humans is probably dominated by other factors.


Immunohistochemical localization of barley stripe mosaic virions in infected wheat cells.
Barley stripe mosaic virus particles were localized in ultrathin sections with colloidal gold-labeled specific IgG or antiserum followed by gold-labeled goat anti-rabbit IgG. On the average, 1.5 gold particles were attached per virus rod. A statistical analysis of counts of gold and virus particles showed that the staining procedure was highly reproducible from experiment to experiment and after several independently prepared colloidal gold solutions. The procedure should be useful for the intracellular localization of any protein to which an antibody can be prepared.


Analysis of corneal topography in patients with pure microphthalmia in Eastern China.
To determine the typical corneal changes in pure microphthalmia using a corneal topography system and identify characteristics that may assist in early diagnosis. Patients with pure microphthalmia and healthy control subjects underwent corneal topography analysis (Orbscan IIZ® Corneal Topography System; Bausch and Lomb, Bridgewater, NJ, USA) to determine degree of corneal astigmatism (mean A), simulation of corneal astigmatism (sim A), mean keratometry (mean K), simulated keratometry (sim K), irregularities in the 3 - and 5-mm zone, and mean thickness of nine distinct corneal regions. Patients with pure microphthalmia (n = 12) had significantly higher mean K, sim K, mean A, sim A, 3.0 mm irregularity and 5.0 mm irregularity, and exhibited significantly more false keratoconus than controls (n = 12). There was a significant between-group difference in the morphology of the anterior corneal surface and the central curvature of the cornea. Changes in corneal morphology observed in this study could be useful in borderline situations to confirm the diagnosis of pure microphthalmia.


Naloxone does not antagonize leukocytic pyrogen.
In a crossover experiment, cats were given third cerebral ventricular injections of 500 microgram naloxone hydrochloride or saline vehicle followed in 15 min by i.v. injections of saline solution or leukocytic pyrogen. The pyrogen produced comparable fevers after both saline and naloxone pretreatment. Intravenous administration of naloxone hydrochloride (5 mg/kg) likewise did not prevent febrile responses to leukocytic pyrogen. These results indicate that endogenous opioid peptides are not likely central mediators of pyrogen-induced fevers.


Induction of immunogenic cell death by novel platinum-based anticancer agents.
Traditional platinum-based anticancer drugs, led by cisplatin, play an important role in chemotherapy. However, the development of platinum compounds is limited due to serious toxicity and side effects. In recent years, studies have showed that immunogenic cell death (ICD) may be one of the potential action mechanisms of classical platinum drugs, such as oxaliplatin. This strategy combining chemotherapy and immunotherapy can effectively utilize the body's immune system to help platinum compounds to fight against tumors, and the dose can be appropriately reduced to limit toxic side effects. The induction of ICD by platinum compounds has become a research hotspot and one of the future development directions of metal drugs. Here, the progress of platinum compounds were collected and comprehensively summarized, their capacity of ICD induction and mechanism of action are exposed, providing reference for the design and synthesis of new anticancer platinum ICD inducers.


Effluent toxicity test using developmental stages of the marine polychaete Hydroides elegans.
The US Environmental Protection Agency (USEPA) has established a suite of methods that use coastal invertebrate species as bioassay organisms to test industrial and domestic effluent as well as coastal waters for potential toxicity. Although these methods are used globally, the potential of such toxicity tests has not been adequately explored for Asian coastal waters. This study describes bioassay utilizing the gametes of Hydroides elegans to monitor coastal water quality and is based on the sensitivity of H. elegans embryo and larva to different concentrations of effluents and water samples collected from different regions of east coast of India. Among the water samples collected from different regions, seawater from Ennore station showed decrease in percentage of development, and 25% effluent concentration led to development arrest of H. elegans embryos. The different morphological effects produced by effluents clearly reflect the defect in early differentiation of embryonic cells. Since fertilization can be inhibited in the presence of any xenobiotic, both fertilization and early development can be used as a biological indicator for a rapid bioassay to monitor pollution. Toxicity tests utilizing early life stages of H. elegans are suitable for the assessment of effects produced by low levels of pollutants due to their high sensitivity to various contaminants relative to other marine species and also due to the relative simplicity of the bioassay.


The Supplemental Nutrition Assistance Program (SNAP): History, Politics, and Public Health Implications.
This commentary introduces a special section of AJPH on the Supplemental Nutrition Assistance Program (SNAP), the US government's largest antihunger program and third-largest antipoverty program. SNAP demonstrably lifts adults, children, and families out of poverty, thereby constituting a vital component of this nation's public health safety net.Despite its well-documented benefits, SNAP is under political and budgetary siege, mainly from congressional representatives and lobbying groups opposed to a federal role in welfare. In part, SNAP is protected from total annihilation by its unusual authorizing legislation-the Farm Bill.This commentary provides a brief overview of the political history of SNAP and its Farm Bill location as background to the deeper analyses provided in this series of articles.


Characterization of miR-335-5p and miR-335-3p in human osteoarthritic tissues.
We aimed to characterize the expression patterns, gene targets, and functional effects of miR-335-5p and miR-335-3p among seven primary human knee and hip osteoarthritic tissue types. We collected synovial fluid, subchondral bone, articular cartilage, synovium, meniscus/labrum, infrapatellar/acetabular fat, anterior cruciate ligament/ligamentum teres, and vastus medialis oblique/quadratus femoris muscle (n = 7-20) from surgical patients with early- or late-stage osteoarthritis (OA) and quantified miR-335-5p and miR-335-3p expression by real-time PCR. Predicted gene targets were measured in knee OA infrapatellar fat following miRNA inhibitor transfection (n = 3), and prioritized gene targets were validated following miRNA inhibitor and mimic transfection (n = 6). Following pathway analyses, we performed Oil-Red-O staining to assess changes in total lipid content in infrapatellar fat. Showing a 227-fold increase in knee OA infrapatellar fat (the highest expressing tissue) versus meniscus (the lowest expressing tissue), miR-335-5p was more abundant than miR-335-3p (92-fold increase). MiR-335-5p showed higher expression across knee tissues versus hip tissues, and in late-stage versus early-stage knee OA fat. Exploring candidate genes, VCAM1 and MMP13 were identified as putative direct targets of miR-335-5p and miR-335-3p, respectively, showing downregulation with miRNA mimic transfection. Exploring candidate pathways, predicted miR-335-5p gene targets were enriched in a canonical adipogenesis network (p = 2.1e - 5). Modulation of miR-335-5p in late-stage knee OA fat showed an inverse relationship to total lipid content. Our data suggest both miR-335-5p and miR-335-3p regulate gene targets in late-stage knee OA infrapatellar fat, though miR-335-5p appears to be more prominent, with tissue-, joint-, and stage-specific effects.


Mobile Learning in Medical Education.
Currently, mobile learning is a new trend in medical education. Therefore, the aim of this study is to examine the use of m-learning in medical education and discuss its effect on student learning process in order to help future medical professionals deliver better care for patients and populations. This was done by conducting a literature search in the databases Web of Science, Scopus, and MEDLINE, and consequently by evaluating the findings of the selected studies. The results of this study confirm that mobile learning is efficient, especially in the acquisition of new knowledge and skills. Nevertheless, so far, the role of mobile learning has been perceived as an appropriate complement to traditional learning. Therefore, more research should be conducted on the efficacy of the use mobile learning in medical education, as well as to explore the unique features of mobile devices for the enhancement of learning outcomes.


Eight undescribed steroidal saponins including an unprecedented 16, 26-epoxy-furostanol saponin from Solanum xanthocarpum and their cytotoxic activities.
Eight undescribed steroidal saponins named solasaponins A-H were isolated from the fruits of Solanum xanthocarpum, including an unusual 16,26-epoxy-furostanol saponin, two furostanol saponins, three isospirostanol saponins, two pseudo-spirostanol saponins. The structures of all compounds were elucidated by extensive spectroscopic data analyses (1D, 2D NMR, and HRESIMS) combined with physico-chemical analysis methods (acid hydrolysis, optical rotation, and IR). The cytotoxicities of all compounds in vitro against two human cancer cell lines (A-549 and HepG2) were evaluated by CCK-8 assay.


Arterial and venous cerebral blood flow responses to long-term head-down bed rest in male volunteers.
What is the central question of this study? A heterogeneous cerebral blood flow (CBF) response in the cerebral arteries has been demonstrated in several physiological conditions, and it might be attributable to different physiological properties. However, the whole cerebral haemodynamic response to weightlessness remains unknown. What is the main finding and its importance? Long-term head-down bed rest caused a heterogeneous CBF response between the anterior and posterior cerebral arteries and between the cerebral arteries and veins. Especially, in contrast to the anterior cerebral circulation, the posterior arterial and venous CBFs were well maintained throughout weightlessness. In this study, we investigated the whole cerebral haemodynamic response to long-term head-down bed rest (HDBR). We hypothesized that long-term exposure to weightlessness influences cerebral blood flow (CBF) or CBF distribution among cerebral arteries and veins because of the different physiological roles of each cerebral vessel. To test this hypothesis, 10 male volunteers were exposed to -6 deg HDBR for 60 days. Blood flows in the internal carotid artery, external carotid artery and vertebral artery or internal jugular vein and vertebral vein were measured using ultrasonography before and on days 30 and 57 of the HDBR. The internal carotid artery blood flow was reduced on day 30 (P = 0.019) and had returned to the baseline level by day 57. In contrast, the vertebral artery blood flow remained unaltered throughout the HDBR (P = 0.626). The internal jugular vein blood flow was reduced on day 30 (P = 0.009), whereas the vertebral vein blood flow remained unaltered (P = 0.397). These findings suggest that long-term HDBR causes a heterogeneous CBF response between the anterior and posterior cerebral circulation in the both arteries and veins. The posterior arterial and venous CBFs were well maintained throughout HDBR, and these CBF responses to HDBR were different from the anterior cerebral circulation.


Fluorimetric study of the artificial chaperone-assisted renaturation of carbonic anhydrase: a kinetic analysis.
It is now well accepted that ionic detergents along with alpha- or beta-cyclodextrins can enhance protein refolding yields. In this report, we evaluated the effect of detergent's tail length on the kinetics of denatured carbonic anhydrase refolding along with determining the rate-limiting step of the whole refolding process. A sensitive fluorimetric technique was also developed to follow up the second-by-second fate of the denatured protein while undergoing refolding. In this technique, inclusion complexes are formed between the correctly refolded CA and the fluorescent active site probe, 5-dimethylaminonaphtalene-1-sulfonamide. By this specific technique, it became evident that the rate of detergent stripping from the CA-detergent mixed micelles that also appeared to be the rate-limiting step depends on the beta-CD-detergent association constants which are under the influence of detergent's tail length. Based on these findings, appropriate refolding conditions could be designed to kinetically diminish the rate of off-pathway aggregation.


Therapeutic potential of pharmacological agents targeting TRP channels in CNS disorders.
Central nervous system (CNS) disorders like Alzheimer's disease (AD), Parkinson disease (PD), stroke, epilepsy, depression, and bipolar disorder have a high impact on both medical and social problems due to the surge in their prevalence. All of these neuronal disorders share some common etiologies including disruption of Ca2+ homeostasis and accumulation of misfolded proteins. These misfolded proteins further disrupt the intracellular Ca2+ homeostasis by disrupting the activity of several ion channels including transient receptor potential (TRP) channels. TRP channel families include non-selective Ca2+ permeable channels, which act as cellular sensors activated by various physio-chemical stimuli, exogenous, and endogenous ligands responsible for maintaining the intracellular Ca2+ homeostasis. TRP channels are abundantly expressed in the neuronal cells and disturbance in their activity leads to various neuronal diseases. Under the pathological conditions when the activity of TRP channels is perturbed, there is a disruption of the neuronal homeostasis through increased inflammatory response, generation of reactive oxygen species, and mitochondrial dysfunction. Therefore, there is a potential of pharmacological interventions targeting TRP channels in CNS disorders. This review focuses on the role of TRP channels in neurological diseases; also, we have highlighted the current insights into the pharmacological modulators targeting TRP channels.