Laparoscopic extraperitoneal colostomy in elective abdominoperineal resection for cancer: a single surgeon experience.
Parastomal herniation of end colostomies can be chronically debilitating for patients and a difficult problem to treat. To prevent parastomal hernia (PSH) formation an extraperitoneal colostomy (EPC) approach has been developed in open colorectal surgery and some studies have suggested a potential advantage to this approach. Here we describe our technique of laparoscopic extraperitoneal stoma formation and present our experience to date. We performed a retrospective analysis of consecutive patients undergoing a laparoscopic abdominoperineal resection between March 1999 and March 2011. We performed the EPC technique as follows: under laparoscopic guidance, a smooth tip instrument was used to gently separate the peritoneum from the posterior aponeurotic plane to create an extraperitoneal tunnel running from the skin incision to the left flank of the abdominal cavity to join the previously dissected paracolic gutter. The colon was exteriorized and the position was checked to ensure the absence of torsion or kinking. Twenty-two patients underwent a standard laparoscopic abdominoperineal resection with total mesorectal excision. Colostomy was constructed extraperitoneally (EPC) or transperitoneally (TPC) in 12 and 10 patients respectively. There were five complications requiring operative intervention: two stomal necrosis and one surgical site infection in the TPC group and two small bowel occlusions in the EPC group. Four patients from the TPC group developed PSH at 24, 36, 48 and 72 months respectively while there were no cases of PSH in the EPC group. Extraperitoneal laparoscopic colostomy showed a potential reduction of PSH in our series of patients.


Neuroprotective action of α-Klotho against LPS-activated glia conditioned medium in primary neuronal culture.
The α-Klotho is an anti-aging protein that, when overexpressed, extends the life span in humans and mice. It has an anti-inflammatory and protective action on renal cells by inhibiting NF-κB activation and production of inflammatory cytokines in response to TNF-α. Furthermore, studies have shown the neuroprotective effect of α-Klotho against neuroinflammation on different conditions, such as aging, animal models of neurodegenerative diseases, and ischemic brain injury. This work aimed to evaluate the effects of α-Klotho protein on primary glial cell culture against the proinflammatory challenge with LPS and how this could interfere with neuronal health. Cortical mixed glial cells and purified astrocytes were pretreated with α- α-Klotho and stimulated with LPS followed by TNFα, IL-1β, IL-6, IFN-γ levels, and NF-κB activity analysis. Conditioned medium from cortical mixed glia culture treated with LPS (glia conditioned medium (GCM) was used to induce neuronal death of primary cortical neuronal culture and evaluate if GCM-KL (medium from glia culture pretreated α-Klotho followed by LPS stimulation) or GCM + LPS in the presence of KL can reverse the effect. LPS treatment in glial cells induced an increase in proinflammatory mediators such as TNF-α, IL-1β, IL-6, and IFN-γ, and activation of astrocyte NF-κB. GCM treated-cortical neuronal culture induced a concentration-dependent neuronal death. Pretreatment with α-Klotho decreased TNF-α and IL-6 production, reverted NF-κB activation, and decreased neuronal death induced by GCM. In addition, KL incubation together with GCM + LPS completely reverts the neuronal toxicity induced by low concentration of GCM-LPS. These data suggest an anti-inflammatory and neuroprotective effect of α-Klotho protein in the CNS. This work demonstrated the therapeutic potential of α-Klotho in pathological processes which involves a neuroinflammatory component.


[Target-controlled infusion (TCI) - a concept with a future?: state-of-the-art, treatment recommendations and a look into the future].
Over the last 10 years the technique of target-controlled infusion (TCI) has substantially influenced the development and practice of intravenous anaesthesia. It opened the possibility of many new and exciting applications of perioperative anaesthetic care. More recent and current developments, such as open TCI (target-controlled infusion) and the availability of generic anaesthetic agents combined with modern infusion pumps, means that TCI can become a standard procedure in anaesthesia and is no longer just a research tool for specialists and enthusiasts. This review explains the fundamentals and applications of intravenous drug delivery by TCI and gives practice guidelines to successfully implement the technique into clinical practice. The aim is to provide a comprehensive reference based on clinically proven evidence.


Recurrent meningitis associated with Duane syndrome type I.
We present the case of a 17-month-old male patient with a bilateral Duane syndrome type 1 associated to unilateral cochleovestibular dysplasia, perilymphatic fistula and recurrent meningitis. Diagnosis was carried out by MRI and CT scan. His management and treatment are described, as well as the postoperative evolution. We believe this is an exceptional case due to the low frequency of this syndrome, as well as to the otoneurological complications.


Neonatal exposure to bisphenol analogues disrupts genital development in male mice.
The public concern and governmental regulations on bisphenol A (BPA) have stimulated the development and production of alternative analogues to replace BPA in a myriad of applications. Given the endocrine disrupting activities of BPA and potentially other analogues, the present study investigated and compared the effects of neonatal exposure to BPA, BPB, BPE, BPF, and BPS on the genital development in male mice. Pups were injected subcutaneously on the right shoulder in the mornings of postnatal days P0.5, P2, P4, and P6, resulting in a low dose of 0.05 μg/g body weight (bw)/day and a high dose of 10 μg/g bw/day. Mice were sacrificed at predetermined time and evaluated for gene expression levels (3 days after birth or P3), steroid hormone levels (P5), and morphological changes (P21). The results demonstrated that BPA, BPB, BPE, or BPF significantly shortened glans penis length and anogenital distance, while BPS didn't. Testis weight and anogenital distance were also significantly affected by BPA, BPE or BPF. The results also revealed that bisphenol analogues exposure significantly reduced testosterone levels, and altered the expression levels of developmental genes networks in developing penis of mice. Our data demonstrate that selected bisphenol analogues may possess similar endocrine disrupting effects compared to BPA, and exposure to these analogues could affect reproductive development of male mice. This raises the concern on the environmental and health safety of bisphenol analogues applied as industrial BPA replacements.


First-in-Human Study of Acoustic Angiography in the Breast and Peripheral Vasculature.
Screening with mammography has been found to increase breast cancer survival rates by about 20%. However, the current system in which mammography is used to direct patients toward biopsy or surgical excision also results in relatively high rates of unnecessary biopsy, as 66.8% of biopsies are benign. A non-ionizing radiation imaging approach with increased specificity might reduce the rate of unnecessary biopsies. Quantifying the vascular characteristics within and surrounding lesions represents one potential target for assessing likelihood of malignancy via imaging. In this clinical note, we describe the translation of a contrast-enhanced ultrasound technique, acoustic angiography, to human imaging. We illustrate the feasibility of this technique with initial studies in imaging the hand, wrist and breast using Definity microbubble contrast agent and a mechanically steered prototype dual-frequency transducer in healthy volunteers. Finally, this approach was used to image pre-biopsy Breast Imaging Reporting and Data System (BI-RADS) 4 and 5 lesions <2 cm in depth in 11 patients. Results indicate that sensitivity and spatial resolution are sufficient to image vessels as small as 0.2 mm in diameter at depths of ~15 mm in the human breast. Challenges observed include motion artifacts, as well as limited depth of field and sensitivity, which could be improved by correction algorithms and improved transducer technologies.


[Doppler ultrasonic probe and oscillograph in phlebology practice].
The ultrasonic or Doppler probe must become a routine instrument in phlebology. It makes it possible to not only to demonstrate arterial circulatory disorders, but also to approximately estimate the level of secondary effects on the peripheral circulation. Once he knows that there is an arterial pathology, the phlebologist can then decide whether to apply a compressive bandage, to prescribe a degressive support stocking, to inject sclerosing drugs or to resort to foot surgery.


Long intergenic non-coding RNA Linc00485 promotes lung cancer progression by modulating miR-298/c-Myc axis.
Long non-coding RNAs (lncRNAs), which are non-protein-coding transcripts, are emerging as novel biomarkers for cancer diagnosis. Their dysregulation is increasingly recognized to contribute to the development and progression of human cancers, including lung cancer. Linc00485 is a newly discovered cancer-related lncRNA; however, little is known about its role in lung cancer progression. In this study, we found that the expression of Linc00485 was significantly increased in human lung cancer tissue and associated with malignant phenotypes, including tumour-node-metastasis (TNM) stage, metastasis and relapse. Furthermore, the proliferative, migratory and invasive abilities of lung cancer cells in vitro were significantly enhanced by overexpression of Linc00485 but inhibited by its silencing. Mechanistically, Linc00485 regulated the expression of c-Myc by directly binding to miR-298; the effects of Linc00485 overexpression could be significantly reversed by a c-Myc inhibitor or small interfering RNA. Xenotransplantation experiments showed that Linc00485 silencing significantly weakened the proliferation potential of A549 cells in vivo. Overall, these findings indicate that Linc00485 overexpression down-regulates miR-298, resulting in the up-regulation of c-Myc and thereby promoting the development of lung cancer.


The effects of different dobutamine infusion rates on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs.
Previously, we demonstrated that dobutamine was more effective than dopamine for the improvement of diaphragmatic contractility during hypercapnia. Here, we studied the effects of different dobutamine infusion rates on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs. Animals were divided into four groups of six each. In each group, hypercapnia (80-90 mm Hg) was produced by adding 10% CO2 to inspired gas. When hypercapnia was established, group Dob 0 received no study drug; group Dob 5 was induced with dobutamine 5 microg x kg(-1) x min(-1); group Dob 10 was induced with dobutamine 10 microg x kg(-1) x min(-1); group Dob 15 was induced with dobutamine 15 microg x kg(-1) x min(-1). Study drugs were administered IV for 60 min. Diaphragmatic contractility was assessed by measurement of transdiaphragmatic pressure (Pdi). In the presence of hypercapnia, in each group, Pdi at low-frequency (20 Hz) and high-frequency (100 Hz) stimulation decreased from baseline (P < 0.05). In group Dob 0, Pdi to each stimulus did not change from hypercapnia-induced values. In groups Dob 5, Dob 10 and Dob 15, during the study drug administration, Pdi at both stimuli increased from hypercapnia-induced values (P < 0.05). There was a significant positive correlation between dobutamine infusion rates and Pdi at both stimuli (P = 0.0001). Dobutamine effectively improves hypercapnic depression of diaphragmatic contractility in an infusion rate-dependent manner in pentobarbital-anesthetized dogs.


Frontiers in optical imaging of cerebral blood flow and metabolism.
In vivo optical imaging of cerebral blood flow (CBF) and metabolism did not exist 50 years ago. While point optical fluorescence and absorption measurements of cellular metabolism and hemoglobin concentrations had already been introduced by then, point blood flow measurements appeared only 40 years ago. The advent of digital cameras has significantly advanced two-dimensional optical imaging of neuronal, metabolic, vascular, and hemodynamic signals. More recently, advanced laser sources have enabled a variety of novel three-dimensional high-spatial-resolution imaging approaches. Combined, as we discuss here, these methods are permitting a multifaceted investigation of the local regulation of CBF and metabolism with unprecedented spatial and temporal resolution. Through multimodal combination of these optical techniques with genetic methods of encoding optical reporter and actuator proteins, the future is bright for solving the mysteries of neurometabolic and neurovascular coupling and translating them to clinical utility.


Absorbability of calcium sources: the limited role of solubility.
Fractional absorption of seven chemically defined calcium sources was measured in normal adult women under standardized load conditions. Solubility of the sources in water at neutral pH ranged from a low of 0.04 mM to a high of 1500 mM. The relationship of solubility to absorbability was weak. In the range from 0.1 to 10 mM, within which most calcium supplement sources fall, there was no detectable effect of solubility on absorption. Data from four food sources are presented for comparison. Absorbability of food calcium was not clearly related to absorbability of the dominant chemical form in the food concerned. These findings suggests that (1) even under controlled, chemically defined conditions, solubility of a source has very little influence on its absorbability; and (2) absorbability of calcium from food sources is determined mainly by other food components.


Levamisole inhibits in vivo rat platelet aggregation by a release of prostacyclin-like factor.
1. The anti-thrombotic effect of levamisole (LMS) and acetylsalicylic acid (ASA) were examined in vitro and in vivo models. 2. LMS inhibits rat platelet aggregation induced by either adenosine 5'-diphosphate (ADP) or collagen (CLG) in vitro and in vivo. 3. LMS is more active in vivo than in vitro while acetylsalicylic acid (ASA) is more active in vitro than in vivo. It seems that in vivo LMS does not act by blocking thromboxane A2 formation only, but via participation of an endogenous factor. 4. The release of LMS-induced anti-thrombotic factor is inhibited by ASA pretreatment, indicating to be a cyclooxygenase metabolite of arachidonic acid. 5. The LMS-induced anti-thrombotic factor has a t1/2 of 3.6 +/- 0.8 min that is similar to the t1/2 of synthetic prostacyclin (PGI2) tested in our system (3.9 +/- 0.5 min; P = NS). 6. The release of PGI2-like substance from vascular tissue is LMS dose-dependent.


Parasitic rachiopagus conjoined twins with herniation of the autosite spinal cord into the parasite: case report.
A female newborn was found to have a rachiopagus parasite consisting of hypoplastic lower limbs attached to the dorsal thoracolumbar region; at surgery, when the infant was 30 days old, the autosite spinal cord was found to have herniated through a spina bifida into the parasite.


Are marketed topical metronidazole creams bioequivalent? Evaluation by in vivo microdialysis sampling and tape stripping methodology.
To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence. Nine microdialysis probes were inserted in the volar aspect of the left forearm of 14 healthy volunteers and, following application of the 3 metronidazole creams, microdialysis samples were collected for 5 h. On the right forearm, tape strip sampling was performed 30 and 120 min after product application. At the end of the experiment, ultrasound scanning measurements confirmed that all probes were placed inside the dermis. There was no statistical difference in penetration of the 3 topicals as determined by microdialysis. However, their bioequivalence could not be determined due to intersubject variability exceeding the criteria for bioequivalence evaluation. Tape strip sampling established a bioequivalence between 2 of the creams, but rejected any bioequivalence between these 2 formulations and the third. The third formulation was a generic formulation approved despite containing a lower concentration of metronidazole (0.75%) than the innovator formulation (1.0%). The result of the bioequivalence evaluation depends on the methodology employed. Whenever the dermis is the target tissue, microdialysis provides the most relevant information on drug bioavailability.


Relaxation time, interthiol distance, and mechanism of action of ribosomal protein S1.
The two sulfhydryl groups of ribosomal protein S1 from Escherichia coli have been labeled with fluorescent maleimides and the distance between them has been determined by nonradiative energy transfer. This distance was found to be approximately 27 A for both free S1 and S1 bound to 30 S subunits. This value probably represents an upper limit. The position of the fluorescence emission maximum indicates that both sulfhydryl groups are in a relatively hydrophobic environment. When poly(U) is added to labeled S1, either free or in 30 S subunits, the emission maximum shifts to the red by about 3 nm but without a detectable change in the interthiol distance. S1 labeled at one or both of its sulfhydryl groups retains most of its ability to enhance poly(U)-directed polyphenylalanine synthesis. About the same concentration of poly(U) is required to give the maximum shift in fluorescence as is required to give maximum polyphenylalanine synthesis, indicating that S1 binds poly(U) during translation. The peptide initiation inhibitor aurintricarboxylic acid almost completely quenches the fluorescence from either labeled sulfhydryl groups in S1 bound to ribosomes or free in solution. This quenching probably is due to energy transfer from the labeled sulfhydryls to bound aurintricarboxylic acid. Fluorescence anisotropy measurements indicated that the C-terminal domain of S1 is relatively rigid, but retains some independent movement when attached to ribosomes. The overall data are consistent with a model in which a region near the two sulfhydryl groups in the elongated C-terminal domain functions to sequester and bind mRNA to the ribosome during peptide synthesis.


Cellulose nanofiber from pomelo spongy tissue as a novel particle stabilizer for Pickering emulsion.
For the high-value utilization of agricultural wastes to promote sustainable development, in this work, pomelo spongy tissue cellulose nanofibers (PCNFs) with lengths >3 μm and widths 33-64 nm were prepared by high pressure homogenization (HPH). The PCNFs were used to stabilized Pickering emulsion, and the emulsion with oil phase fraction in the range of 10 % to 50 % (w/w) exhibited outstanding stability. The increase in PCNFs concentration also enhanced the three-dimensional network structure, resulting in higher stability of the emulsion. Moreover, the droplet size distribution of emulsion would be greatly improved by moderate heating. No creaming was observed in emulsions over a wide range of ionic strengths (20-200 mM) after storage for 30 d. And the excellent emulsifying properties of the PCNFs were mainly attributed to their adsorption at the oil-water interface and the formation of a three-dimensional network structure. All the results indicated that the PCNF would be a promising novel stabilizer for Pickering emulsions.


The differential effect of the anxiolytic agent 8-OH-DPAT during lactation is independent of pup withdrawal and maternal behavior.
Injection of the serotonergic agonist, 8-hydroxy-2-(di-n-propylamino-tetralin (8-OH-DPAT) (0.5 mg/kg ip) produced a clear anxiolytic-like effect (as measured in the burying behavior test), after parturition, which remains until day 6 of lactation. Thereafter 8-OH-DPAT completely lacked action. In order to analyze whether lactation prevented the action of 8-OH-DPAT, dams were separated from their pups for five consecutive days. The blockade of the anxiolytic effect of 8-OH-DPAT does not disappear by isolation of the mothers from their offspring or from neighboring pups. Finally, to investigate the possible role of maternal behavior in the blockade of the anxiolytic effect of 8-OH-DPAT a third experiment was made in which ovariectomized females were rendered maternal by the sensitization procedure. These females respond normally to the antianxiety actions of 8-OH-DPAT. Results suggest that a long-term clue triggered by lactation, possibly related to prolactin secretion, interferes with the anxiolytic effect of 8-OH-DPAT.


[A case of severe recurrent transient granulocytopenia during hemofiltration: possible pathogenetic interpretations].
The authors report a case of severe granulocytopenia without increased susceptibility to infections in a patient with IRC (chronic renal failure) on hemofiltration treatment. The possible pathogenetic mechanisms are examined. The phenomenon is probably due to an altered compartmentation of neutrophils; the temporariness and the quick correction of the granulocytopenia explain the lack of clinical manifestations.


The action of lung lysosomal phospholipases on dipalmitoyl phosphatidylcholine and its significance for the synthesis of pulmonary surfactant.
Subcellular fractions were prepared from rabbit lung and characterized by marker enzyme assays. Phospholipases A of lysosomal type (activity at pH 4.0 in the absence of Ca2+) show a peak of specific activity in fraction P3 (13000 x g; 20 min; pellet). About 70% of the phospholipase A activity of P3 can be obtained in a soluble extract. The rates of hydrolysis of dipalmitoyl (saturated) and unsaturated phosphatidylcholine molecules, presented to enzyme preparations in liposomes of varying composition, are shown in Tables 3 to 5. Although the rate of unsaturated molecules is unaffected by liposome composition, saturated molecules are hydrolyzed significantly faster in 5 mol % dipalmitoyl phosphatidylcholine liposomes than in 95 mol %. With enzyme preparation I (60% A1: 40% A2) the increase was 6-fold (P less than 0.01). Preparations I and II hydrolyzed both kinds of molecules at similar rates in 50 mol % dipalmitoyl phosphatidylcholine liposomes, but preparation III, with a higher proportion of A2 (80%), gave a notably lower rate of hydrolysis of saturated molecules. Phosphatidylglycerol (10 mol %) also decreased the rate of hydrolysis of saturated molecules. These results are discussed in relation to fluidity of the liposomes and to the functions of the lysosomal-type phospholipases A of the lamellar inclusion bodies of the lung.


Promoting access to renal transplantation: the role of social support networks in completing pre-transplant evaluations.
Completing pre-transplant evaluations may be a greater barrier to renal transplantation for blacks with end-stage renal disease (ESRD) than for whites. To determine whether social support networks facilitate completing the pre-transplant evaluation and reduce racial disparities in this aspect of care. We surveyed 742 black and white ESRD patients in four regional networks 9 months after they initiated dialysis in 1996 and 1997. Patients reported instrumental support networks (number of friends or family to help with daily activities), emotional support networks (number of friends or family available for counsel on personal problems) and dialysis center support (support from dialysis center staff and patients). The completion of pre-transplant evaluations, including preoperative risk stratification and testing, was determined by medical record reviews. Complete renal pre-transplant evaluations. Compared to patients with low levels of instrumental support, those with high levels were more likely to have complete evaluations (25% versus 46%, respectively, p < .001). In adjusted analyses, high levels of instrumental support were associated with higher rates of complete evaluations among black women (p < .05), white women (p < .05), and white men (p < .05), but not black men. Among black men, but not other groups, private insurance was a significant predictor of complete evaluations. Instrumental support networks may facilitate completing renal pre-transplant evaluations. Clinical interventions that supplement instrumental support should be evaluated to improve access to renal transplantation. Access to supplemental insurance may also promote complete evaluations for black patients.


Synchronous diagnosis of colorectal malignancy and lymphoma.
To perform case series from one centre over 9 years, and review of the literature. The synchronous diagnosis of colorectal malignancy and lymphoma is rare. Case note review of patients identified from clinical databases. Five patients were identified and findings discussed. In two patients colorectal malignancy staging CT scans identified pathological lymphadenopathy consistent with lymphoma. A further two patients had an incidental lymphoma on histological examination of the colorectal malignancy specimen. The fifth patient was found to have suspicious superior mesenteric lymph nodes at laparotomy. Histology confirmed two nodular lymphocyte-predominant Hodgkin's lymphomas, a lymphocytic-rich classical Hodgkin's lymphoma, a diffuse large B-cell lymphoma and a B-cell follicular lymphoma. There is a need for vigilance for the possibility of dual pathologies in all specialties.


Agreement between patient interview data on prescription medication use and pharmacy records in those aged older than 50 years varied by therapeutic group and reporting of indicated health conditions.
To estimate the agreement between interview-ascertained medication use and pharmacy records among the population aged older than 50 years, and to identify patient-level predictors of discordance. The Irish Longitudinal study on Ageing is representative of community-dwelling adults aged 50 years and older in Ireland. Interview-ascertained medication data from 2,621 participants were linked to pharmacy dispensing records. The kappa statistics measured the agreement between the two sources for 19 therapeutic classes. Logistic regression assessed the effect of patient-level characteristics on survey under- and overreporting of regularly dispensed medications. Agreement was good or very good (κ=0.64-0.86) for 15 medication classes, and moderate or poor for antiinflammatory and antirheumatic products (κ=0.54), analgesics (κ=0.50), psycholeptics (κ=0.59), and ophthalmologicals (κ=0.37). Not reporting an indicated health condition, less frequent dispensing, older age, and more medications regularly dispensed were associated with survey underreporting, but results varied by therapeutic class. Memory and cognition were not associated with discordance. Ascertaining medication use via patient interview seems a valid method for most medication classes and also captures nonprescription and supplement use. However, medications applied topically and as needed may be underreported. The source of medication data should be carefully considered when performing pharmacoepidemiological studies.


A novel, dual role of CCN3 in experimental glomerulonephritis: pro-angiogenic and antimesangioproliferative effects.
In contrast to factors that promote mesangial cell proliferation, little is known about their endogenous inhibitors. During experimental mesangioproliferative nephritis, expression of the glomerular CCN3 (nephroblastoma overexpressed gene [NOV]) gene is reduced before the proliferative phase and increased in glomeruli and serum when mesangial cell proliferation subsides. To further elucidate its role in mesangioproliferative glomerulonephritis, CCN3 systemically was overexpressed by muscle electroporation in healthy or nephritic rats. This increased CCN3 serum concentrations more than threefold for up to 56 days. At day 5 after disease induction, CCN3-transfected rats showed an increase in glomerular endothelial area and in mRNA levels of the pro-angiogenic factors vascular endothelial growth factor and PDGF-C. At day 7, CCN3 overexpression decreased mesangial cell proliferation, including expression of α-smooth muscle actin and matrix accumulation of fibronectin and type IV collagen. In progressive nephritis (day 56), overexpression of CCN3 resulted in decreased albuminuria, glomerulosclerosis, and reduced cortical collagen type I accumulation. In healthy rat kidneys, overexpression of CCN3 induced no morphologic changes but regulated glomerular gene transcripts (reduced transcription of PDGF-B, PDGF-D, PDGF-receptor-β, and fibronectin, and increased PDGF-receptor-α and PDGF-C mRNA). These data identify a dual role for CCN3 in experimental glomerulonephritis with pro-angiogenic and antimesangioproliferative effects. Manipulation of CCN3 may represent a novel approach to help repair glomerular endothelial damage and mesangioproliferative changes.


Global transmission and reflection coefficients of the ultrasonic component in porous media: a new approach.
The purpose of this paper is to propose a new approach to determining the global ultrasonic transmission and reflection coefficients in a random porous medium. Boundary conditions at the interface of the medium were used to determine local transmission and reflection coefficients. A study of the behavior of different waves inside the medium was carried out to derive a new global formulation that takes interior phenomena into consideration. All the results were obtained independently of the geometrical and physical characteristics of the medium so that the method can be applied to any two-phase porous medium. This study is based on normal incidence ultrasonic wave propagation.


Improving survival disparities in cervical cancer between Māori and non-Māori women in New Zealand: a national retrospective cohort study.
Māori women in New Zealand have higher incidence of and mortality from cervical cancer than non-Māori women, however limited research has examined differences in treatment and survival between these groups. This study aims to determine if ethnic disparities in treatment and survival exist among a cohort of Māori and non-Māori women with cervical cancer. A retrospective cohort study of 1911 women (344 Māori and 1567 non-Māori) identified from the New Zealand Cancer Register with cervical cancer (adenocarcinoma, adenosquamous or squamous cell carcinoma) between 1 January 1996 and 31 December 2006. Māori women with cervical cancer had a higher receipt of total hysterectomies, and similar receipt of radical hysterectomies and brachytherapy as primary treatment, compared to non-Māori women (age and stage adjusted). Over the cohort period, Māori women had poorer cancer specific survival than non-Māori women (mortality hazard ratio (HR) 2.07, 95% confidence interval (CI): 1.63-2.62). From 1996 to 2005, the survival for Māori improved significantly relative to non-Māori. Māori continue to have higher incidence and mortality than non-Māori from cervical cancer although disparities are improving. Survival disparities are also improving. Treatment (as measured) by ethnicity is similar. Primary prevention and early detection remain key interventions for addressing Māori needs and reducing inequalities in cervical cancer in New Zealand.


Residue formation of fumonisin B1 in porcine tissues.
The residues derived from the uptake of fumonisin B1, a toxic metabolite of Fusarium verticillioides frequently occurring in corn and corn products, were determined in growing pigs. After oral administration of 100 mg FB(1)/animal/day for 5-11 days, serum, bile, lung, liver, kidney, brain, spleen, pancreas, heart, muscle, eye, and fat samples were collected immediately and analysed by LC-MS. The highest values were measured in kidney (833 +/- 1329 microg kg(-1), mean +/- SD), liver (231 +/- 163 microg kg(-1)), lung (170 +/- 311 microg kg(-1)) and spleen (854 +/- 2212 microg kg(-1)). Muscle contained 26 +/- 41 microg kg(-1), while in fat only 2 +/- 3 microg kg(-1) were traceable. Despite the potential accumulation over extended feeding periods as well as the large variations in the residue formation of FB(1), a carry-over in edible tissues from swine was considered not to be of toxicological relevance.


Insights into the estimation of surface tensions of mixtures based on designable green materials using an ensemble learning scheme.
Precise estimation of the physical properties of both ionic liquids (ILs) and their mixtures is crucial for engineers to successfully design new industrial processes. Among these properties, surface tension is especially important. It's not only necessary to have knowledge of the properties of pure ILs, but also of their mixtures to ensure optimal utilization in a variety of applications. In this regard, this study aimed to evaluate the effectiveness of Stochastic Gradient Boosting (SGB) tree in modeling surface tensions of binary mixtures of various ionic liquids (ILs) using a comprehensive dataset. The dataset comprised 4010 experimental data points from 48 different ILs and 20 non-IL components, covering a surface tension range of 0.0157-0.0727 N m-1 across a temperature range of 278.15-348.15 K. The study found that the estimated values were in good agreement with the reported experimental data, as evidenced by a high correlation coefficient (R) and a low Mean Relative Absolute Error of greater than 0.999 and less than 0.004, respectively. In addition, the results of the used SGB model were compared to the results of SVM, GA-SVM, GA-LSSVM, CSA-LSSVM, GMDH-PNN, three based ANNs, PSO-ANN, GA-ANN, ICA-ANN, TLBO-ANN, ANFIS, ANFIS-ACO, ANFIS-DE, ANFIS-GA, ANFIS-PSO, and MGGP models. In terms of the accuracy, the SGB model is better and provides significantly lower deviations compared to the other techniques. Also, an evaluation was conducted to determine the importance of each variable in predicting surface tension, which revealed that the most influential factor was the mole fraction of IL. In the end, William's plot was utilized to investigate the model's applicability range. As the majority of data points, i.e. 98.5% of the whole dataset, were well within the safety margin, it was concluded that the proposed model had a high applicability domain and its predictions were valid and reliable.


Angioinvasive pulmonary mucormycosis presenting as multiple bilateral pulmonary nodules in a patient without obvious predisposing factors.
Pulmonary mucormycosis is a rare, frequently fatal, fungal infection. It is usually seen in the presence of various immunocompromised states, such as diabetes mellitus, haematological malignancy or renal transplantation. In the absence of underlying predisposing conditions, presentation with infiltrates, consolidation, cavitation and mass lesion have been reported. We describe a 50-year-old man who presented with cough and chest pain for six months. Chest radiograph and computed tomography showed bilateral multiple pulmonary nodules. Surgical lung biopsy revealed angioinvasive mucormycosis. He had complete recovery with amphotericin therapy.


Making therapies culturally relevant: translation, cultural adaptation and field-testing of the Thinking Healthy Programme for perinatal depression in China.
The prevalence of perinatal depression in China ranges from 15 to 20% and the vast majority of prenatally depressed women do not receive the intervention they require. Recent research evidence shows that evidence based, culturally-adapted psychosocial interventions are effective in reducing mental health problems. The World Health Organization (WHO) has endorsed the Thinking Healthy Programme (THP), which is an evidence based psychosocial intervention that can be delivered by non-mental health specialists. The aim of this study was to translate and adapt THP for the Chinese population and to establish its acceptability when delivered by non-specialists to a group of mothers with perinatal depression. The study was conducted in two phases. The THP manual, handbook, and health calendar was translated and adapted based on 8 domains of the Bernal framework (language, metaphors, content, concepts, goals, context, people and methods). Pre-testing was done using cognitive interviewing in the first phase. In second phase of field-testing, THP sessions were delivered to the depressed women by local THP trained nurses. Post intervention, programme survey was used for evaluation. This study showed that the core structure, process and techniques of the THP were culturally compatible with the target Chinese population and did not require major changes. It was found that the adapted version of THP manual, handbook, and health calendar were acceptable, understandable, and culturally relevant to the Chinese women and their family members. Nurses were found as a suitable delivery agent by the mothers and their families. The Thinking Healthy Programme is acceptable and transferable to the Chinese cultural and healthcare context and nurses are a suitable delivery agent. The translated and adapted version of THP can be used for further implementation and evaluation studies in the Chinese context. Further evaluation can help establish the effectiveness of the programme and barriers to scale-up in China.


Low birthweight and premature birth are both associated with type 2 diabetes in a random sample of middle-aged Danes.
We studied the associations of size at birth and prematurity with type 2 diabetes, insulin sensitivity and beta cell function in the Danish population-based Inter99 study (ClinicalTrials.gov NCT00289237). Information about size at birth and prematurity was identified from original midwife records in 4,744 middle-aged Danes. Type 2 diabetes status, insulin sensitivity (Matsuda index) and beta cell function (disposition index) were assessed using a 75 g oral glucose tolerance test. Participants born prematurely were compared with a group of at-term participants born small for gestational age. An increase in birthweight of 1 kg was associated with a 51% (OR 0.49, 95% CI 0.35-0.69) reduced risk of type 2 diabetes. Ponderal index, reflecting thinness at birth, was associated with type 2 diabetes to the same extent as birthweight. The prevalence of type 2 diabetes was increased to a similar degree in participants born prematurely and participants born small for gestational age, although the former had a higher ponderal index at birth. In addition, birthweight z-scores, reflecting fetal growth rate, were unrelated to the risk of type 2 diabetes and to other measures of glucose regulation in participants born prematurely. While low birthweight was inversely associated with insulin sensitivity and beta cell function, prematurity was associated solely with decreased insulin sensitivity. While the association between birthweight and risk of type 2 diabetes is mediated via combined effects on beta cell function and insulin sensitivity, prematurity seems to influence risk of type 2 diabetes via attenuated insulin sensitivity only and independently of fetal growth rates.


Crystal structure of NOD2 and its implications in human disease.
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a member of the NOD-like receptors family, are crucial for innate immune responses. Mutations of NOD2 have been associated with chronic inflammatory disorders such as Crohn's disease (CD), Blau syndrome (BS) and early-onset sarcoidosis (EOS), but little is known about its signalling mechanism and the role it plays in these diseases. Here, we report the crystal structure of rabbit NOD2 in an ADP-bound state. The structure reveals an inactive closed conformation in which the subdomains in the NOD domain are closely packed by ADP-mediated and inter-domain interactions. Mapping of the BS- or EOS-associated gain-of-function mutations reveals that most of these mutations are located in the NOD subdomain interfaces, and are likely to disrupt the inner domain interactions, facilitating a conformational change to the active form. Conversely, mutations associated with CD are distributed throughout the protein, some of which may affect oligomer formation and ligand binding.


Editorial Commentary: A Biphasic (Calcified and Demineralized), Cancellous, Interpositional Allograft Augmenting Rotator Cuff Repair in an Ovine Model Does Not Show Harmful Inflammation or Foreign Body Reaction.
To improve the outcomes of arthroscopic rotator cuff (RC) repair, it is important to achieve tendon-to-bone healing at the repair site. Healed repairs are more likely to restore shoulder strength and lead to higher magnitudes of satisfaction. Patches or grafts that can be either secured to the bursal surface of the RC or interposed between the RC tendon and greater tuberosity at the time of repair have been described as adjuncts to RC repair. A cancellous, biphasic allograft tissue composed of 2 layers (calcified to promote osseointegration and demineralized to support soft-tissue ingrowth) has been shown to be safe in an ovine model, without a harmful inflammatory or foreign body response. Human trials may be a reasonable next step.


Soluble Expression of Antimicrobial Peptide BSN-37 from Escherichia coli by SUMO Fusion Technology.
Antimicrobial peptides (AMPs) are a kind of small molecular peptide that an organism produces to resist the invasion of foreign microorganisms. AMP BSN-37 is a bovine AMP that exhibits high antibacterial activity. In this paper, the optimized gene AMP BSN-37 was cloned into pCold-SUMO for fusion expression by recombinant DNA technology. The gene sequence of AMP BSN-37 was obtained by codons reverse translation, and the codons were optimized according to the codons preference of Escherichia coli (E. coli). The recombinant plasmid was constructed and identified by PCR, enzyme digestion and sequencing. Then the recombinant plasmid was transformed into BL21 E. coli to induce expression, and the IPTG concentration and time were optimized. The expressed soluble fusion protein SUMO-BSN-37 was purified by chromatography and then cleaved by SUMO proteases to release BSN-37. SDS-PAGE electrophoresis and Western blotting were used for identification. The recombinant plasmid pCold-SUMO-BSN-37 was obtained, and the fusion AMP BSN-37 was preliminarily expressed in BL21. After optimization, the optimal expression condition was 37 ℃ with 0.4 µM IPTG and 6 h incubation. Under optimal conditions, a large amount of fusion AMP BSN-37 was obtained by purification. Western blotting showed that the fusion peptide was successfully expressed and had good activity. The expressed BSN-37 showed antimicrobial activity similar to that of synthesized BSN-37. In this study, soluble expression products of AMP BSN-37 were obtained, and the problem regarding the limited source of AMP BSN-37 could be effectively solved, laying a foundation for further research on AMP BSN-37.


Factors influencing the incidence of Hirschsprung associated enterocolitis (HAEC).
This study aims to characterize risk factors for Hirschsprung-associated enterocolitis (HAEC). We hypothesize that earlier pull-through surgery is associated with lower risks of developing postoperative HAEC. A comparative study of 171 Hirschsprung patients treated from 1990 to 2017 was performed. Patients without HAEC were compared to patients with preoperative and/or postoperative HAEC. Results are presented as median [IQR] or frequency (%). Pearson's χ2 test and Wilcoxon rank sum test were performed with a significance level at p < 0.05. Multivariable logistic regression analysis was used to adjust for potential confounders. A subanalysis was done to evaluate laparoscopic, laparotomy, and transanal surgeries. Risk of developing preoperative HAEC was significantly associated with congenital malformations (OR 2.63 [1.11, 6.24]; p = 0.02). Birth weight was lower in patients with preoperative HAEC (OR 0.48 [95% CI 0.25, 0.93]; p = 0.03). On regression analysis, intestinal obstruction after surgery was significantly associated with postoperative HAEC (OR 8.2 [3.18, 21.13]; p < 0.0001). Patients with earlier pull-through surgery did not have a lower risk of developing postoperative HAEC. Timing of surgery does not seem to be associated with a higher risk of developing pre- and postoperative HAEC. Predisposing factors for preoperative HAEC included associated malformations and lower birth weight, whereas intestinal obstruction was found to be associated with postoperative HAEC. Treatment study. Level III.


A phase II trial of preoperative mitomycin, cisplatin and 5-fluorouracil in adenocarcinoma of the oesophagus.
The effect of neoadjuvant chemotherapy in patients with apparently operable adenocarcinoma of the oesophagus has been investigated. Two courses of mitomycin, cisplatin and 5-fluorouracil (MCF) were given, followed by a radiological evaluation of response. Twenty-two of 25 patients completed both courses. Two showed a complete response and 12 a partial response. There was a pathological complete response of the primary tumour in only one patient (although there was residual secondary tumour in a local lymph node). The main toxicity was myelosuppression, with 9/22 patients having the second chemotherapy course delayed. There were three sudden deaths, one due to a pulmonary embolus and two due to complications of infections. Twenty-one patients underwent surgical exploration; there were 18 resections. Although the radiological response rate of MCF (14/25; 56%; 95% CI 37-75) appeared promising, there were no pathological complete responders. Further Phase II trials are needed to identify more efficacious agents and regimens that will yield a pathological response rate of at least 10%, before proceeding to randomized trials of neoadjuvant chemotherapy for adenocarcinoma of the oesophagus.


Intermolecular Paramagnetic Relaxation Enhancement (PRE) Studies of Transient Complexes in Intrinsically Disordered Proteins.
NMR interchain paramagnetic relaxation enhancement (PRE) techniques are a very powerful approach for detecting transient interchain interactions between intrinsically disordered proteins. These experiments, requiring a mixed sample containing a 1:1 ratio of isotope-labeled (15)N protein and natural abundance (14)N protein with a paramagnetic spin label, provide data that is limited to interchain interactions only. Application of these experiments to weakly associated transient species such as those that are present in the very early stages of self-assembly processes will aid our understanding of protein aggregation or fibril formation processes.


The molecular and genetic dissection of the retinoid signalling pathway.
Retinoids are derivatives of vitamin A (retinol) that exert a wide variety of profound effects on vertebrate development, cellular differentiation and homeostasis. How these simple molecules can exert such pleiotropic effects has recently been an area of intensive investigation. A complex array of combinatorial effects is beginning to emerge from molecular and genetic studies, which may ultimately account for the pleiotropic effects of retinoids.


[Method of early detection of adolescents and young adults at high risk for alcoholism for the purpose of primary prevention of alcoholism].
Using the Pathocharacterological Diagnostic Inventory (PDI) a total of 264 teenagers were examined to identify among 15-17-year-olds a group at a high risk of beginning to drink alcohol beverages before coming of age. A follow-up study in two years revealed that 16% of them became alcohol abusers. Comparison of the results obtained with the help of the PDI in abstainers versus alcohol abusers has demonstrated that a high risk group is readily identified using a special scale of psychological liability to alcoholization.


Concanavalin A binding capacity of preimplantation mouse embryos.
Mouse embryos collected on Days 2 (2-cell) to 4 (early blastocyst) were treated with pronase to digest the zona pellucida and cultured at 37 degrees C for 3 h. These embryos and untreated Day-5 late blastocysts were exposed to [3H]Con A at 25, 50, 100 or 200 microgram/ml, 4 degrees C for 30 min, washed and counted for radioactivity. Other groups of embryos were incubated with [3H]Con A in the presence of 0.06 M-alpha-methyl-D-mannoside for the detection of non-specific binding. Scatchard plot analysis showed that the total number of Con A molecules bound/embryo increased with development, from 12 X 10(7) in 2-cell embryos to 19 X 10(7) in early blastocysts and to 150 X 10(7) in late blastocysts. The association constants decreased from 3 X 10(6) M-1 in 2-cell embryos to 0.83 X 10(6) M-1 in late blastocysts. The results suggest that the Con A binding sites (probably glycoproteins) on the embryo surface change quantitatively and qualitatively during preimplantation development.


Enhanced proliferation of aortal smooth muscle cells treated by 1,25(OH)2D3 in vitro coincides with impaired formation of elastic fibres.
Elastin is the major extracellular matrix component synthesized, secreted and deposited by vascular smooth muscle cells (SMCs) in the arterial media and thus plays an important role in vascular homeostasis. Results of our previous studies showed that 1alpha,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)-calcitriol] accelerates proliferation of SMCs and modulates their growth in vitro. The aim of this study was to find ultrastructural support for the idea that 1,25(OH)(2)D(3)-calcitriol affects elastic fibre formation due to accelerated proliferation of aortal SMCs in vitro. SMCs exposed 10 days to supraphysiological concentration (10 nM) of calcitriol in primary culture were examined by fluorescence and transmission electron microscopy. Morphological studies revealed that calcitriol altered elastin maturation by favouring accumulation of immature rather than fully processed elastic fibres. A substantial decrease in the amorphous elastin deposition and abnormal accumulation of microfibrillar component, in thickened multilayer culture, were observed. These studies suggest that 1,25(OH)(2)D(3) affect formation of elastic fibres due to enhanced proliferation of SMCs in culture.


L-Cysteine hydrochloride inhibits Aspergillus flavus growth and AFB1 synthesis by disrupting cell structure and antioxidant system balance.
Aflatoxin B1 (AFB1) is the most potent known naturally occurring carcinogen and pose an immense threat to food safety and human health. L-Cysteine hydrochloride (L-CH) is a food additive often used as a fruit and vegetable preservative and also to approved bread consistency. In this study, we investigated the effects and mechanisms of L-CH as an antimicrobial on the growth of Aspergillus flavus (A. flavus) and AFB1 biosynthesis. L-CH significantly inhibited A. flavus mycelial growth, affected mycelial morphology and AFB1 synthesis. Furthermore, L-CH induced glutathione (GSH) synthesis which scavenged intracellular reactive oxygen species (ROS). RNA-Seq indicated that L-CH inhibited hyphal branching, and spore and sclerotia formation by controlling cell wall and spore development-related genes. Activation of the GSH metabolic pathway eliminated intracellular ROS, leading to hyphal dwarfing. L-CH treatment downregulated most of the Aflatoxin (AF) cluster genes and aflS, aflR, AFLA_091090 transcription factors. This study provides new insights into the molecular mechanism of L-CH control of A. flavus and AFB1 foundation. We believe that L-CH could be used as a food additive to control AFB1 in foods and also in the environment.


Surprises in the energetics of host-guest anion binding to calix[4]pyrrole.
Contrary to common expectation, calorimetric measurements do not corroborate the preference of calix[4]pyrrole for fluoride over chloride in acetonitrile solution.


A forespore checkpoint for mother cell gene expression during development in B. subtilis.
Gene expression in the mother cell compartment of sporulating cells of B. subtilis is partly governed by the mother cell RNA polymerase sigma factor sigma K. Paradoxically, sigma K-directed gene expression also depends on sigma G, the product of the forespore compartment regulatory gene spoIIIG, and on other forespore regulatory proteins. We now identify mutations in the genes bofA and bofB that relieve the dependence of mother cell gene expression on forespore regulatory proteins but not on sigma K. We establish that the dependence of mother cell gene expression on the forespore regulatory proteins is mediated at the level of the conversion of pro-sigma K to its mature, active form. We propose that the bofA and/or bofB proteins govern this conversion in response to a signal generated by the forespore. Activation of pro-sigma K could be a checkpoint for coordinating gene expression between the mother cell and forespore compartments of the developing sporangium.


Teaching of posterior composites for the restoration of permanent teeth in undergraduate dental training programmes: Systematic review and meta-analysis.
To systematically assess aspects of teaching of posterior composite restorations (PCRs) in permanent teeth in dental schools. Quantitative studies reporting on dental schools' teaching regarding the placement of PCRs in permanent teeth. Random-effects meta-analyses and meta-regressions were performed. Risk of bias was assessed based on the Medical Education Research Study Quality Instrument (MERSQI). Electronic databases (MEDLINE via PubMed, EMBASE via Ovid, Web of Science, and Scopus) were searched in January 2023. Forty sources reporting on 34 studies having surveyed 1,286 dental schools were included. Overall, 92.7% (95%-CI: 88.2-95.5) of dental schools reported to teach PCRs. PCRs in three-surface Class II cavities are taught by 82.0% (95%-CI: 70.4-89.7). The mandatory use of liners in deep cavities is taught by 78.3% (95%-CI: 68.9-85.5), and 44.0% (95%-CI: 34.3-54.2) reported to teach bulk-fill composites. While most posterior restorations placed by students were composites (56.1%; 95%-CI: 46.0-65.8), 94.7% (95%-CI: 86.6-98.0) of dental schools (still) teach posterior amalgam restorations. The proportion of dental schools teaching PCRs in three-surface Class II cavities increased and the mean proportion of PCRs among all posterior restorations increased over time (padj.≤0.003). The teaching of PCRs in dental schools around the world reflects the increased use of resin composite in clinical practice, with students in countries where dental amalgam continues to be used, placing more posterior composites than restorations of dental amalgam. The teaching of PCRs, which is anticipated to increase, will continue to be refined with further developments in adhesive materials, devices, instrumentation, and techniques. Graduating dentists can be expected to be familiar with the use of resin composites for the restoration of posterior teeth.


Rapid 1-hour transduction of whole bone marrow leads to long-term repopulation of murine recipients with lentivirus-modified hematopoietic stem cells.
Efficient gene transfer to hematopoietic stem cells by Moloney murine leukemia virus-derived retroviral vectors benefits from ex vivo culture and cytokine support. Both also increase the risks of apoptosis and differentiation among cells targeted for transduction. In an effort to maximize the retention of stem cell properties in target cells, we developed a transduction protocol with a focus on minimizing graft manipulation, cytokine stimulation, and ex vivo exposure duration. Based on their wide host range and ability to transduce quiescent cells, human immunodeficiency virus (HIV)-derived lentivirus vectors are ideally suited for this purpose. Our present studies in a murine model show that whole bone marrow cells are readily transduced after a 1-hour vector exposure in the presence of stem cell factor and CH296 fibronectin fragment. Using this rapid transduction protocol, we achieved long-term, multilineage reconstitution of murine recipients with up to 25% GFP-expressing cells in primary and secondary recipients. Our results demonstrate the unique ability of HIV-derived vectors to transduce hematopoietic stem cells in the absence of enrichment, under minimal cytokine stimulation, and following brief exposures.


Barriers in implementing research among registered nurses working in the care of the elderly: a multicenter study in Spain.
This study identified barriers to the utilization of research results perceived by nurses who work in nursing homes in Spain. An observational, cross-sectional, descriptive, and multicentre study was conducted in 126 nursing homes in different Spanish cities. The BARRIERS to Research Utilization Scale (BARRIERS scale) was used to identify barriers. A total of 756 nurses responded (92.48%). BARRIERS scale variables with the highest scores included Characteristics of the organization (mean=24.89, SD=4.37), followed by Professional features (mean=21.87, SD=4.85). The specific barriers that were rated the highest included "not enough time on the job to implement new ideas" (mean=3.89, SD=0.98), followed by "unknown nursing research" (mean=2.75; SD=1.22) and "Doctors do not cooperate in the implementation" (mean=3.01, SD=1.85). Geriatric nurses perceive time as the main barrier to implementing the results of research in practice. The number and nature of the barriers are consistent with studies from other countries. Knowledge of the barriers is crucial for institutions and educators to instigate measures that improve the implementation of nursing research, especially in an area like elderly care. To our knowledge, this is the first study conducted among geriatric nurses in Spain.


Towards bio-compatible magnetic nanoparticles: Immune-related effects, in-vitro internalization, and in-vivo bio-distribution of zwitterionic ferrite nanoparticles with unexpected renal clearance.
Iron oxide and other ferrite nanoparticles have not yet found widespread application in the medical field since the translation process faces several big hurdles. The incomplete knowledge of the interactions between nanoparticles and living organisms is an unfavorable factor. This complex subject should be made simpler by synthesizing magnetic nanoparticles with good physical (relaxivity) and chemical (colloidal stability, anti-fouling) properties and no biological activity (no immune-related effects, minimal internalization, fast clearance). Such an innocent scaffold is the main aim of the present paper. We systematically searched for it within the class of small-to-medium size ferrite nanoparticles coated by small (zwitter)ionic ligands. Once established, it can be functionalized to achieve targeting, drug delivery, etc. and the observed biological effects will be traced back to the functional molecules only, as the nanosized scaffold is innocent. We synthesized nine types of magnetic nanoparticles by systematic variation of core composition, size, coating. We investigated their physico-chemical properties and interaction with serum proteins, phagocytic microglial cells, and a human model of inflammation and studied their biodistribution and clearance in healthy mice. The nanoparticles have good magnetic properties and their surface charge is determined by the preferential adsorption of anions. All nanoparticle types can be considered as immunologically safe, an indispensable pre-requisite for medical applications in humans. All but one type display low internalization by microglial BV2 cells, a process strongly affected by the nanoparticle size. Both small (3 nm) and medium size (11 nm) zwitterionic nanoparticles are in part captured by the mononuclear phagocyte system (liver and spleen) and in part rapidly (≈1 h) excreted through the urinary system of mice. The latter result questions the universality of the accepted size threshold for the renal clearance of nanoparticles (5.5 nm). We suggest that it depends on the nature of the circulating particles. Renal filterability of medium-size magnetic nanoparticles is appealing because they share with small nanoparticles the decreased accumulation-related toxicity while performing better as magnetic diagnostic/therapeutic agents thanks to their larger magnetic moment. In conclusion, many of our nanoparticle types are a bio-compatible innocent scaffold with unexpectedly favorable clearance.


Modulating the actions of NK cell-mediated cytotoxicity using lipid-PEG (n) and inhibitory receptor-specific antagonistic peptide conjugates.
Regulating the cell surface modulates the actions of the biological cell response, derives practical applications, and is of scientific interest. On the basis of our previous study using dioleylphosphatidylethanolamine poly(ethylene glycol) with multiple units of ethyleneoxide (DOPE-PEG (n)), we demonstrated the potency of DOPE-PEG (80) as a cell surface modulator. We prepared conjugates of DOPE-PEG (80) and two antagonistic peptides (C1, SGGGCLFNLPWLCG; C26, SGGGCPFSFLPWCG), specifically designed for the inhibitory receptor of natural killer (NK) cells. We confirmed that NK cells exhibited cytotoxicity against DOPE-PEG (80)-peptides-incorporated target cells. We further investigated whether the DOPE-PEG (80)-peptides could affect the cytotoxicity of NK cells in a concentration-dependent manner. C1 peptide showed down-regulation of cytotoxicity at higher concentration, whereas C26 peptide exhibited the saturated cytotoxicity of NK cells at the same concentration. These results suggest that DOPE-PEG (80) can achieve the role of a cell surface modulator without inhibiting the action of conjugated molecules, despite their relatively small size.


Stratification of inspired air in the elongated lungs of the carpet python, Morelia spilotes variegata.
Using lung gas tensions via a triple lumen catheter to monitor ventilation distribution (VA) and radioactive techniques to study blood flow distribution (Q), the distribution of ventilation to perfusion ration (VA/Q) was studied in the elongated alveolar lung of the Carpet Python, Morelia spilotes variegata. In the resting, sleeping and agitated states both alveolar oxygen (PAO2) and carbon dioxide tensions (PACO2) were 'stratified' (unevenly distributed) within the alveolar lungs at end inspiration, during breath holding for up to 6 minutes and, when VA was low, at end expiration. The blood flow was also stratified. The degree of stratification of VA was influenced by the rate and depth of breathing and the length of the breath hold which preceeded the gas sampling. Similar results were obtained with a glass lung model. In both resting and sleeping states VA/Q ratios were similar over the proximal 75% of the alveolar lungs whereas VA nearly always exceeded Q over the distal 25%. The anatomic features of the lung are proposed as a possible mechanism for maintaining a uniform VA/Q distribution. Since the anatomical arrangement places the heart at the apical regions of the lungs, absence of cardiac mixing, combined with low respiratory rates, enables stratification to continue for very long periods within the aveolar lungs of the snake.


The potential effects of clinical antidiabetic agents on SARS-CoV-2.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is currently posing significant threats to public health worldwide. It is notable that a substantial proportion of patients with sever COVID-19 have coexisting diabetic conditions, indicating the progression and outcome of COVID-19 may relate to diabetes. However, it is still unclear whether diabetic treatment principles can be used for the treatment of COVID-19. We conducted a computational approach to screen all commonly used clinical oral hypoglycemic drugs to identify the potential inhibitors for the main protease (Mpro ) of SARS-CoV-2, which is one of the key drug targets for anti-COVID-19 drug discovery. Six antidiabetic drugs with docking scores higher than 8.0 (cutoff value), including repaglinide, canagliflozin, glipizide, gliquidone, glimepiride, and linagliptin, were predicted as the promising inhibitors of Mpro . Interestingly, repaglinide, one of the six antidiabetic drugs with the highest docking score for Mpro , was similar to a previously predicted active molecule nelfinavir, which is a potential anti-HIV and anti-COVID-19 drug. Moreover, we found repaglinide shared similar docking pose and pharmacophores with a reported ligand (N3 inhibitor) and nelfinavir, demonstrating that repaglinide would interact with Mpro in a similar way. These results indicated that these six antidiabetic drugs may have an extra effect on the treatment of COVID-19, although further studies are necessary to confirm these findings.


Clinical Efficacy of Persian Medicine Diet Combined with Western Medicine-Based Diet on Proteinuria in Pediatric Nephrotic Syndrome: A Randomized Controlled Clinical Trial.
Nephrotic syndrome (NS) is a common chronic kidney disorder during childhood. The most important characteristic of this disease is proteinuria. The Persian medicine (PM) has important dietary recommendations for strengthening the kidney function and treatment of this disease. The aim of this study was to investigate the effect of a diet including PM recommendations and general principles of Western medicine. Twenty children with nephrotic syndrome were randomly divided into intervention and control groups and monitored for one month. The control group received a diet based on the general principles of Western medicine. In the intervention group, in addition to the Western medicine diet, dietary recommendations of PM were also prescribed including the pomegranate (Cydonia oblonga mill.), quince (Cydonia oblonga mill.), and whole grains (wheat and barley). A 24-hour dietary questionnaire was applied and anthropometric and biochemical indices including spot urine protein (proteinuria), albumin (Alb), urea, creatinine (Cr), total cholesterol (TC), and triglyceride (TG) were measured before and after the study. The amount of protein intake reduced significantly in the diet of both groups but the differences between the two groups were not significant. Proteinuria reduced significantly in both the Western and PM groups; however, proteinuria was significantly lower in the Persian medicine group compared to the control group. TC and Cr levels reduced significantly in the intervention group, although the changes were not significant compared to the control group. The results of this study showed that adding dietary recommendations of the Persian medicine to the general rules of the Western medicine diet reduced proteinuria and improved the combat against nephrotic syndrome.


Fructose restrains fibrillogenesis in human serum albumin.
The endogenous deposition of protein aggregates with fibrillar morphology is known to govern the genesis of several neurodisorders. The investigation of naturally occurring small molecules which can restrict the fibrillation process can help in the design of rational therapeutics for neurodegenerative diseases. We report the inhibition of HSA fibrillation in the presence of naturally occurring sugars such as glucose, fructose, ribose and sucrose with fructose being the most potent. We have characterized the inhibitory potency of the sugars, using different spectroscopic and microscopic techniques.


Impulse control disorders and pathological gambling in patients with Parkinson disease.
The primary aim of this article is to critically review the clinical features and comorbidities, epidemiology, pathophysiology, and treatment of impulse control disorder (ICD) associated with Parkinson disease (PD). References for this review were identified by searches of PubMed from 1980 until January 2008 with the terms "Parkinson disease," "impulse control," "pathologic gambling,""hypersexuality," "levodopa," and "dopamine agonists." Articles were also identified through searches of the authors' own files. Only papers published in English were reviewed. Pathologic gambling has emerged as one of the most prominent ICDs, although hypersexuality, compulsive shopping and other manifestations of obsessive-compulsive disorder may also dominate PD-related behavioral manifestations. Affected patients may demonstrate a pattern of self-escalation of dopaminergic medication dosing which may lead to a state of dependency. Patients most commonly affected by ICD, such as pathologic gambling and hypersexuality, are males who develop PD at a younger age, and those with a previous history of mood disorder, alcohol abuse, or obsessive-compulsive disorder. Dopaminergic drugs, particularly dopamine agonists, play an important role in triggering these nonmotor symptoms.


Total and differential ionization cross sections in collision between nitrogen atom and singly charged sodium ion.
We present a theoretical study of the ionization of nitrogen atom by a singly charged sodium ion using the classical trajectory Monte Carlo method. Although we suffer from a lack of cross section data of this collision system, the knowledge of the basic cross sections is essential in fusion science, because this reaction has potential applications in the diagnostic of magnetically confined fusion plasmas. In our investigations, the Na+-N collision system is reduced to a three-body problem. The interaction between the collision partners is described by the Garvey-type model potential. The results of our study provide insight into the dynamics of singly charged sodium-nitrogen interactions. The total cross sections are presented in the impact energy range between 10 keV and 10 MeV and compared them with the available experimental data. The single and double differential cross sections are presented at 30, 40, 50 and 60 keV energies related to the energies of the plasma diagnostic used in the nuclear fusion.


Ligand-induced reactivity of β-diketiminate magnesium complexes for regioselective functionalization of fluoroarenes via C-H or C-F bond activations.
Using β-diketiminate Mg(ii) complexes containing either alkyl, aryl or amide groups, the regioselective functionalization of a wide range of fluoroarenes is accomplished but in uniquely different ways. Overcoming common limitations of traditional s-block bases, kinetically activated [(DippNacnac)Mg(TMP)] (1) deprotonates these molecules at room temperature, trapping sensitive fluoroaryl anions that can then engage in Negishi cross-coupling; whereas [(DippNacnac)Mg(R)THF] (R = nBu, Ph, benzofuryl) have proved to be effective reagents for C-F bond alkylation/arylation via pyridine directed C-F bond cleavage.


Endoscopic third ventriculostomy for obstructive hydrocephalus in children younger than 6 months of age: is it a first-choice method?
Endoscopic third ventriculostomy (ETV) is considered a safe procedure and is a method of choice in treatment of obstructive hydrocephalus nowadays. In case of Sylvian aqueduct stenosis, the success rate reaches 90%. In children younger than 6 to 24 months, respectively, however, some authors report lower effectiveness ranging between 0% and 64%. The reasons of ETV failure are discussed: hyporesorption in patients with obstruction as a consequence of hemorrhage or infection, suboptimal ETV performance, especially in premature newborns, or the theory of different cerebrospinal fluid circulation in newborn babies. Between January 2005 and December 2006 in our clinic, 14 patients younger than 6 months having presented with obstructive hydrocephalus were treated endoscopically. Obstruction was revealed by preoperative magnetic resonance imaging. The etiology of hydrocephalus was congenital aqueduct stenosis in five patients, posthemorrhagic obstruction in eight patients, and combination of posthemorrhagic and postinfection etiology in one patient. ETV was considered successful when no shunt operation was needed in the patient. ETV was successful in eight patients who experienced regression of signs of intracranial hypertension and were not forced to undergo ventriculo-peritoneal (V-P) shunting. In one patient, a successful repeat ETV was performed. In the remaining six patients, V-P shunt implantation was necessary. Total success rate in our group of patients was 57%. The only complication was subdural hygroma in one patient requiring evacuation. Based on our experience, we recommend ETV as the method of choice in children younger than 6 month of age.


Poly-L-lysine-gold complexes used at different pH are probes for differential detection of glycosaminoglycans and phosphoproteins in the predentine and dentine of rat incisor.
At neutral pH, poly-L-lysine-gold complexes labelled the predentine extensively, whereas in dentine the number of gold complexes was reduced by half. Hyaluronidase pretreatment of the section at pH 6.8, prior to labelling, suppressed most of the staining in predentine and did not affect dentine. In contrast, alkaline phosphatase pretreatment at pH 9 enhanced the gold complex labelling in predentine and removed most of the labelling in dentine. This proves that at pH 7.2, the polyanions which are stained include a heterogeneous population of glycosaminoglycans, located in predentine, and phosphoproteins, visualized in dentine. At acidic pH levels (2.9 and 1.1), the number of scored gold complexes decreased, but the ratio between predentine and dentine labelling remained constant. Hyaluronidase pretreatment removed or firmly reduced the gold complex labelling both in predentine and dentine, whereas alkaline phosphatase pretreatment of the sections at pH 9 prior to labelling did not induce any change. This argues in favour of an increased specificity of polylysine-gold complex staining for glycosaminoglycans, stained at low pH in both predentine and dentine. Differential staining of glycosaminoglycans and phosphoproteins according to the pH provides a useful tool for studying the role played respectively by the two matrix components in dentine mineralization.


An estimate of genetic risk from 8-methoxypsoralen photochemotherapy.
A method based on a combination of cell culture and pharmacokinetic data is explored as a way of estimating the possible genetic risk to man from a mutagenic chemical. 8-methoxypsoralen, which is given to psoriasis patients as part of a photochemotherapy regime, is used, since it represents a 'real-life' situation and possesses properties that make it particularly amenable to this approach. It is concluded that treatment of males for a mean period of 10 years before their spermatozoa were involved in conception would increase the gene mutation rate in the male germ line by a factor of 0.00125. The implications of this for the incidence of sex-linked and dominant disease in man are elaborated and the assumptions and limitations are set out. The fragility of the estimates is emphasized.


Control of hemoglobin synthesis in fetal erythroid cells by L-thyroxine.
Fetal mouse liver cells were incubated in the presence of L-thyroxine, Globin synthesis by cells from the 13th to 15th days of gestation was stimulated by the presence of the hormone. Although protein synthesis by cells from the 17th day of gestation was stimulated, the protein was not identified as globin. A tentative conclusion was drawn that fetal erythroid tissue may be preferentially stimulated by thyroid hormone.


Mucosal injury and inflammation in a model of chronic granulomatous colitis in rats.
The objective of this study was to characterize the acute and chronic inflammation induced by the intramural injection of peptidoglycan-polysaccharide (PG-PS) into the distal colon of genetically susceptible rats. Blood-to-lumen clearance of 51Cr-ethylenediaminetetraacetic acid, colonic myeloperoxidase activity, colon weight, and plasma nitrite and nitrate levels were determined to quantitate colonic mucosal injury, inflammation, and nitric oxide (NO) production, respectively. Intramural injection of PG-PS into the distal colon produced a local biphasic inflammatory response composed of an acute episode 3 days after injection; this was followed by a spontaneous reactivation of chronic granulomatous colitis manifested by colonic thickening, adhesions, and infiltration of the submucosa and muscularis propria with macrophages, neutrophils, and lymphocytes at 3-4 weeks. Mucosal ulcers were evident only at 3 weeks, but hepatic nodules, splenic necrosis, and arthritis were evident at both 3 and 4 weeks after PG-PS injection. PG-PS produced significant increases in colonic mucosal permeability, myeloperoxidase activity, and plasma nitrite and nitrate levels at 3 weeks postinjection compared with controls. PG-PS stimulated the production of nitrite by elicited peritoneal macrophages and neutrophils in vitro. PG-PS produces a chronic granulomatous colitis in rats; this colitis is characterized by enhanced NO production.


Should erectile dysfunction be considered as a marker for acute myocardial infarction? Results from a retrospective cohort study.
The association between erectile dysfunction (ED) and acute myocardial infarction (AMI) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, HIPAA-compliant database and includes complete medical history for more than 17 million managed care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 12,825 ED patients and an equal number of male patients without ED were included in the retrospective cohort study. Logistic regression analyses were performed to assess the adjusted risk of AMI that accounted for age at ED diagnosis, smoking, obesity and medications including ACE inhibitors, beta blockers and statins. The cohort of men with ED were observed to have a two-fold increase in the risk for AMI (OR=1.99, 95% CI=1.17, 3.38) after adjusting for age at ED diagnosis, smoking, obesity, and use of ACE inhibitors, beta blockers and statins. Some evidence of a possible trend toward increased risk was detected by age group. After controlling for the aforementioned covariates and compared to men 30-39 y of age, it was noted that patients 40-44 y of age were 3.8 times more likely to develop an AMI (OR=3.76, 95% CI=1.21, 11.7), 45- to 49-y-old men were also more than three times as likely to have an AMI (OR=3.14, 95% CI=1.03, 9.64), and 50- to 55-y-old patients had a four-fold increased risk of developing AMI (OR=4.04, 95% CI=1.39, 11.7). The risk becomes more pronounced with increasing age, indicating the need for cardiologists and internists to monitor ED patients who may not necessarily present with cardiovascular symptoms.


Fourteen cases of left atrial myxoma with emphasis on related histology.
With the availability of diagnostic ultrasonic equipment, there is an increase in the number of diagnosed cases of left atrial myxoma. Fourteen such patients underwent surgical treatment. One major concern was the possible recurrence of the tumor. Histologic examination revealed that the tumor cells did not invade the muscular layer beyond the layer of elastic fiber adjacent to the endocardium, in all cases. We remove the stalk with the Fossa Ovale when the tumor grows on the Fossa Ovale. When the tumor is attached to the muscular septum or free wall, we remove the stalk with the endocardium and a part of the adjacent myocardial layer. The total resection of the muscular septum may not be necessary as far as the myxoma is concerned.


Effects of PPP1R13L and CD3EAP variants on lung cancer susceptibility among nonsmoking Chinese women.
The pathogenesis of lung cancer in the never-smokers could possibly be different from the one in smokers. PPP1R13L and CD3EAP on chromosome 19q13.3 are mainly involved in apoptosis and transcription. PPP1R13L and CD3EAP variants may be associated with cancer risk. We addressed the effects of variants/haplotypes of PPP1R13L rs1970764 and CD3EAP rs967591 and rs735482 on susceptibility of lung cancer among nonsmoking Chinese women. A hospital-based case-control study consisted of 79 lung cancer cases and 108 cancer-free controls matched by age (±3years), gender, ethnicity and lifetime never-smoking. Genotyping and statistical analysis were performed by using the method of ligase detection reaction coupled with polymerase chain reaction (LDR-PCR) and SHEsis program and SPSS software. The presence of variant A-allele for CD3EAP rs967591 was associated with increased lung cancer risk [GA versus GG, OR (95% CI)=2.53 (1.16-5.48), P=0.02 and GA+AA versus GG, OR (95% CI)=2.46 (1.16-5.20), P=0.02]. Both D' values and r(2) values accorded with marker distances on chromosome 19q13.3. No associations were found for two other individual SNPs and haplotype distributions of three markers in the whole or single. In conclusion, this study suggests that CD3EAP rs967591 variant allele carriers are at increased susceptibility of lung cancer among nonsmoking Chinese women.


Endometrial vascularity by three-dimensional power Doppler ultrasound and cytokines: a complementary approach to assess uterine receptivity.
Uterine receptivity was assessed simultaneously by measurement of vasoactive cytokines possibly involved in development of spiral arteries and by assessment of endometrial and uterine arterial blood flow. The objective was to explore the relationship between cytokine-related dysregulation and endometrial vascularisation in women with repeated implantation failures after in vitro fertilisation embryo transfer (IVF-ET). We studied 40 women with recurrent IVF/ICSI-ET failures, despite replacement of more than 10 embryos of 'good quality', and 8 fertile controls. Three-dimensional ultrasound with power angiography was performed to record the sub-endometrial vascular flow index (VFI) and uterine artery pulsatility index prior to endometrial biopsy at day 21-23 of a monitored natural cycle. Endometrial IL-18, IL-18BP and IL-15 mRNA expression was assessed by real-time PCR, and the number of CD56(+) cells determined by immunochemistry. IL-18 and IL-15 mRNA expression was significantly different between the two groups. The range of variation in vascular imaging data was increased in the implantation failure (IF) group. The mRNA ratio for IL-15, but not the other cytokines, correlated with sub-endometrial vascular flow (r=0.65; p<0.001). This ratio correlated also with the mean number of CD56(+) cells per high-power field (r=0.41; p=0.005). Both IL-18 and IL-18BP mRNA expression was significantly negatively correlated with mean uterine artery pulsatility index (r=-0.37 and -0.43; p=0.02 and 0.01, respectively). Comprehensive ultrasonographic indicators appear to be related to various mechanisms, including insufficient or excessive uterine NK cell recruitment and inadequate endothelial vascular remodelling. New molecular tools may be useful in providing greater precision of uterine receptivity than ultrasonic indicators alone.


The oxidant stress hypothesis of atherogenesis.
Atherosclerosis is the commonest lesion of blood vessels and is responsible for life-threatening events such as myocardial infarction and stroke. In the last two decades a series of excellent studies unraveled biochemical mechanisms that provided the background for a theory of atherogenesis. This theory is centered on foam cells and on free radical-mediated modification of low density lipoprotein (LDL). Foam cells are the main cell type of atherosclerotic lesions and originate from monocytes migrated from blood and from smooth muscle cells of the arterial wall. Foam cells are engulfed of lipids taken from LDL. Paradoxically, accumulation of LDL in developing foam cells does not occur via the classic LDL receptor. Incubation of macrophages with even very high concentrations of LDL does not appreciably increase cholesterol content. Chemically modified LDL easily enter the cells of atherosclerotic plaque via an unregulated receptor, the scavenger receptor. The most studied chemical modification of LDL is that induced by free radicals.


Abdominal wall endometriosis: a rarely anticipated diagnosis: a 16-year experience and brief literature review.
To evaluate cases of endometriosis of the abdominal wall to determine whether the diagnosis was anticipated preoperatively and whether or not the patient had undergone prior surgery. This was a retrospective review of records of patients undergoing surgical resection of abdominal wall endometriosis from 1996-2011. Nine cases were identified. For the 8 cases with a recorded preoperative diagnosis, the clinical diagnosis of endometriosis was recorded preoperatively in only 25% of cases. The most common preoperative diagnosis was neoplasia. Abdominal wall endometriosis remains a difficult diagnosis to make preoperatively. Awareness among gynecologists and consideration of the diagnosis in the differential will potentially decrease the number of cases suspected of malignancy and may alleviate some stress on the patients' part, due to the possibility of a benign diagnosis.


Overexpression of mRNA-binding protein CRD-BP in malignant melanomas.
Wnt/beta-catenin signaling pathway plays an important role in embryogenesis, stem cell maintenance, tumorigenesis and aging. Here, we show that RNA-binding protein, coding region determinant-binding protein (CRD-BP) (a transcriptional target of Wnt signaling pathway), is highly expressed in primary human malignant melanomas and melanoma cell lines with activated Wnt/beta-catenin signaling pathway. Upregulation of CRD-BP is associated with an elevated level of beta-TrCP1 ubiquitin ligase receptor and activation of nuclear transcriptional factors-kappa B (NF-kappaB) signaling. Knockdown of CRD-BP inhibits NF-kappaB activity, induces apoptosis, and suppresses proliferation and tumorigenic properties of melanoma cells.


bHLH-PAS family transcription factor methoprene-tolerant plays a key role in JH action in preventing the premature development of adult structures during larval-pupal metamorphosis.
The biological actions of juvenile hormones are well studied; they regulate almost all aspects of an insect's life. However, the molecular actions of these hormones are not well understood. Recent studies in the red flour beetle, Tribolium castaneum, demonstrated the utility of this insect as a model system to study JH action. These studies confirmed that the bHLH-PAS family transcription factor, methoprene-tolerant (TcMet,) plays a key role in JH action during larval stages. In this study, we investigated the role of TcMet in JH action during larval-pupal metamorphosis. The phenotypes of TcMet RNAi insects shared similarity with the phenotypes of some allatectomized lepidopteran larvae that were attempting to undergo precocious larval-pupal metamorphosis. Knocking-down TcMet during the final instar also disrupted larval-pupal ecdysis, resulting in the development of adultoid underneath the larval skin. However, the loss of TcMet did not completely block remodeling of internal tissues such as midgut. T. castaneum larvae injected with TcMet dsRNA demonstrated a resistance to a JH analog (JHA), hydroprene, irrespective of time and route of application. Knocking-down TcMet also caused down regulation of JH-response genes, JHE and Kr-h1 suggesting that TcMet might be involved in the expression of these genes. Based on the phenotype, gene expression, and JHA action studies in TcMet RNAi insects, this study concludes that Met plays a key role in JH action for preventing the premature development of adult structures during larval-pupal metamorphosis.


Parasitism can be a confounding factor in assessing the response of zebra mussels to water contamination.
Biological responses measured in aquatic organisms to monitor environmental pollution could be also affected by different biotic and abiotic factors. Among these environmental factors, parasitism has often been neglected even if infection by parasites is very frequent. In the present field investigation, the parasite infra-communities and zebra mussel biological responses were studied up- and downstream a waste water treatment plant in northeast France. In both sites, mussels were infected by ciliates and/or intracellular bacteria, but prevalence rates and infection intensities were different according to the habitat. Concerning the biological responses differences were observed related to the site quality and the infection status. Parasitism affects both systems but seemed to depend mainly on environmental conditions. The influence of parasites is not constant, but remains important to consider it as a potential confounding factor in ecotoxicological studies. This study also emphasizes the interesting use of integrative indexes to synthesize data set.


Altered topography of EEG spectral content in schizophrenia.
EEG data were recorded in resting and in specific test conditions designed to activate different regions of the brain in a group (n = 10) of chronic schizophrenics and matched controls. EEG spectral energy was computed using the Fast Fourier Transform and numerical matrices representing the topographic distribution of spectral energy in a specified band were constructed and displayed as color images. Significance Probability Mapping was employed to identify regions of maximal group difference; it was found that the schizophrenic group showed increased low frequency energy (0-7 c/sec) in the frontal regions and increased fast activity (12-32 c/sec) in post-central areas and the left anterior temporal area. The different psychological test conditions were associated with different patterns of energy distribution. The consistency of our findings with other investigations suggests that topographic mapping of brain EEG spectral activity may play a useful role in the functional understanding of schizophrenia.


Stress and the anti-influenza immune response: repeated social defeat augments clonal expansion of CD8(+)T cells during primary influenza A viral infection.
Social disruption stress (SDR) prior to primary influenza A virus (IAV) infection augments memory to IAV re-challenge in a T cell-specific manner. However, the effect of SDR on the primary anti-viral immune response has not been elucidated. In this study, SDR-infected (INF) mice terminated viral gene expression earlier and mounted an enhanced pulmonary IAV-specific CD8(+)T cell response versus controls. Additionally, SDR-INF mice had a more pro-inflammatory lung profile prior to and during infection and an attenuated corticosterone response. These data demonstrate neuroendocrine modification of the lung microenvironment and increased antigen-specific T cell activation, clonal expansion and viral control in stress-exposed mice.


Retinoic acid induced repression of AP-1 activity is mediated by protein phosphatase 2A in ovarian carcinoma cells.
In previous studies we have shown that all-trans retinoic acid (atRA)-treatment of the atRA-sensitive ovarian carcinoma cell line CA-OV3 repressed AP-1 activity by about 50%, while a similar effect was not observed in the atRA-resistant ovarian carcinoma cell line, SK-OV3. These results suggested that the repression of AP-1 activity may be one of the mechanisms by which atRA inhibits the growth of atRA-sensitive CA-OV3 cells. In the present studies, we investigated further the molecular mechanism by which AP-1 activity is repressed by atRA. We show that the repression of AP-1 activity correlates with an increase in JunB protein expression and a decrease in N-terminal phosphorylation of c-Jun. The decrease in N-terminal phosphorylation of c-Jun does not appear to be modulated by JNK or ERK, since their protein expression patterns and kinase activity do not correlate with the repression of AP-1 activity following treatment with atRA. However, the activity of the protein phosphatase PP2A was found to increase 24 h following atRA treatment in CA-OV3 cells. Moreover, the catalytic subunit of PP2A was found to associate with c-Jun in vivo following atRA treatment. Since the inhibition of AP-1 activity following atRA treatment of CA-OV3 cells was abolished in the presence of specific PP2A inhibitors, it is likely that PP2A plays an important role in the atRA-induced repression of AP-1.


Impedance changes according to the degree of atopi dermatitis in mice.
Variations in electrical impedance over frequency might be used to distinguish the degree of atopic dermatitis (AD), even if the mechanisms of the skin barrier impairment due to AD are still unknown. We observed the skin bioimpedance of normal mice and of abnormal mice having atopic with instrument measuring electrical impedance. Electrical impedance was measured from 20 Hz to 1 MHz at many frequencies and normalized with several indices such as IMP, PIX, IMIX, RIX, and et al. to reduce variation in subjects. The results showed the high relationship between subjective score and indices, especially, the capacitance change and impedance ratio, abs(Z(1 kHz))/abs(Z(10 kHz)). These results indicate electrical impedance may be a promising clinical diagnostic tool to monitor prognosis of skin care for atopic dermatitis. Using developed software application we easily acquired complex impedance data from the instrument and got the analysis results for very kinds of frequency. This may be useful in various bioimpedance studies such as skin cancer assessment or body composition analysis, or etc.


Prochlorperazine--an unusual cause of lip ulceration.
A case is reported of a fixed drug eruption due to Prochlorperazine maleate which caused ulceration of the lower lip confirmed by a positive provocation test.


In-vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT).
In the past decade, the use of in-vitro fertilization and embryo transfer (IVF-ET) procedures as a means of treatment of infertility has become a clinical reality. More recently, similar yet differing techniques have been described that further expand options of treatment of infertile couples. This article summarizes recent advances in IVF and compares it with the most widely recognized of these alternatives, gamete intrafallopian transfer (GIFT). In addition to comparing and contrasting these new technologies, the authors attempt to highlight unresolved questions about their use.


Levels, origins and probabilistic health risk appraisal for trace elements in drinking water from Lhasa, Tibet.
Due to the lack of monitoring systems and water purification facilities, residents in western China may face the risk of drinking water pollution. Therefore, 673 samples were collected from Lhasa's agricultural and pastoral areas to reveal the status quo of drinking water. We used inductively coupled plasma-mass spectrometry to determine trace elements concentrations for water quality appraisal, source apportionment, and health risk assessment. The results indicate that concentrations of V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd, Ba, and Pb are below the guidelines, while As concentrations in a few samples exceed the standard. All samples were classified into "excellent water" for drinking purpose based on Entropy-weighted water quality index. Thereafter by principal component analysis, three potential sources of trace elements were extracted, including natural, anthropogenic, and mining activities. It is worth noting that geotherm and mining exploitation does not threaten drinking water safety. Finally, health risks were assessed using Monte Carlo technique. We found that the 95th percentiles of hazard index are 1.80, 0.80, and 0.79 for children, teenagers, and adults, indicating a non-carcinogenic risk for children, but no risks for the latter two age groups. In contrast, the probabilities of unacceptable cautionary risk are 7.15, 2.95 and 0.69% through exposure to Cr, Ni, As, and Cd for adults, children, and teenagers. Sensitivity analyses reveal As concentration and ingestion rate are most influential factors to health risk. Hence, local governments should pay more attention to monitoring and removal of As in the drinking water.


Internal porosities, retentive force, and survival of cobalt-chromium alloy clasps fabricated by selective laser-sintering.
The purpose of this study was to evaluate internal porosities, retentive force values and survival of cobalt-chromium (Co-Cr) alloy clasps fabricated by direct metal laser-sintering (DMLS) and compare them to conventionally cast clasps. Embrasure clasps were digitally designed fitting teeth 35 and 36 on identical metal models (N = 32). Sixteen clasps were fabricated using DMLS (group DMLS) and another sixteen clasps were additively manufactured from wax and then cast from a Co-Cr alloy (group CAST). Internal porosities were examined using micro-focus X-ray (micro-CT) and analyzed applying Kolmogorov-Smirnov test, Mann-Whitney test, and T test (significance level: p < 0.050). A universal testing machine was used to determine the retentive force values at baseline and after 1095, 5475, 10,950 and 65,000 cycles of simulated aging. Data were analyzed employing Kolmogorov-Smirnov test, one-way ANOVA, and Scheffé's post-hoc test (significance level: p < 0.050). Survival was estimated for 65,000 cycles of artificial aging using Kaplan-Meier analysis. Micro-CT analysis revealed a higher prevalence (p < 0.001), but a more homogeneous size and a significantly smaller mean (p = 0.009) and total volume (p < 0.001) of internal porosities for group DMLS. The groups showed mean initial retentive force values of 13.57 N (CAST) and 15.74 N (DMLS), which significantly declined over aging for group CAST (p = 0.003), but not for group DMLS (p = 0.107). Survival was considerably higher for group DMLS (93.8%) than for group CAST (43.8%) after 65,000 cycles of aging. Clasps made by laser-sintering could be an alternative to conventional cast clasps for the fabrication of removable partial denture frameworks.


[Yeast irrigation enhances the nutritional content in hydroponic green maize fodder].
The objective of this study was to evaluate the effect of irrigation with yeasts (Debaryomyces hansenii var. Fabry, Yarowia lipolytica YIBCS002, Yarowia lipolytica var. BCS and Candida pseudointermedia) on the final nutritional content of hydroponic green maize fodder (Zea Zea mays L.), applied at different fodder growth stages (1. seed-seedling stage, 2. seedling-plant 20cm, 3. during all the culture). Irrespective of the fodder growth stages at which they were applied, all yeasts tested enhanced the content of raw protein, lipids, ash, moisture and energy. The percentage of electrolytes (Na, K, Cl, sulphates, Ca and Mg) showed different responses depending on the kind of yeast applied; D. hansenii exhibited the highest increment in all electrolytes, except for phosphorous. We conclude that the addition of yeasts belonging to the genera Debaryomyces, Candida and Yarowia to the irrigation solution of hydroponic systems enhances the nutrient content of green fodder. This kind of irrigation can be applied to generate high commercial value cultures in limited spaces.