The effect of HMG-CoA reductase inhibitors on coenzyme Q10: possible biochemical/clinical implications.
The HMG-CoA reductase inhibitors, also known as statins, have an enviable safety profile; however, myotoxicity and to a lesser extent hepatotoxicity have been noted in some patients following treatment. Statins target several tissues, depending upon their lipophilicity, where they competitively inhibit HMG-CoA reductase, the rate-limiting enzyme for mevalonic acid synthesis and subsequently cholesterol biosynthesis. HMG-CoA reductase is also the first committed rate-limiting step for the synthesis of a range of other compounds including steroid hormones and ubidecarenone (ubiquinone), otherwise known as coenzyme Q(10) (CoQ(10)). Recent interest has focused on the possible role CoQ(10) deficiency may have in the pathophysiology of the rare adverse effects of statin treatment. Currently, there is insufficient evidence from human studies to link statin therapy unequivocally to pathologically significantly decreased tissue CoQ(10) levels. Although statin treatment has been reported to lower plasma/serum CoQ(10) status, few human studies have assessed tissue CoQ(10) status. The plasma/serum CoQ(10) level is influenced by a number of physiological factors and, therefore, has limited value as a means of assessing intracellular CoQ(10) status. In those limited studies that have assessed the effect of statin treatment upon tissue CoQ(10) levels, none have shown evidence of a fall in CoQ(10) levels. This may reflect the doses of statins used, since many appear to have been used at doses below those recommended for their maximum therapeutic effects. Moreover, the poor bioavailability in those peripheral tissues tested may not reflect the effects the agents are having in liver and muscle, the tissues commonly affected in those patients who do not tolerate statins. This article reviews the biochemistry of CoQ(10), its role in cellular metabolism and the available evidence linking possible CoQ(10) deficiency to statin therapy.


Pilot study of a survey to identify the prevalence of and risk factors for chronic neuropathic pain following breast cancer surgery.
To provide a preliminary determination of the prevalence rate of women who suffer from neuropathic pain post breast surgery (PPBS) and explore potential risk factors associated with its development. Prospective, quantitative, longitudinal survey. Breast health clinic in western Canada. A convenience sample of 17 women undergoing breast cancer surgery. The Brief Pain Inventory was administered before surgery and 2 days, 10 days, and 3 months postsurgery. Demographic data also were collected preoperatively. Analysis included determining prevalence of PPBS; descriptive analyses on age, gender, and body mass index (BMI); presence of acute postoperative pain; type of surgery; and two-tailed t tests on age and BMI. The symptom experience of chronic PPBS. Twenty-three percent of the sample developed PPBS. Younger age (50 years or younger), more invasive surgery, acute postoperative pain, and less analgesic use during the acute postoperative period were factors associated with the development of PPBS. Additional research is required to confirm the significance of these potential risk factors in the development of PPBS. Nurses are ideally situated to identify early signs of PPBS. In addition, nurses play a key role in the education of patients and healthcare professionals and can facilitate increased awareness about the possibility of developing PPBS, enabling earlier and more effective treatment of PPBS.


Salary and entry-level requirements for pharmacy technicians compared with other health technologist and technician occupations in Maryland.
Pharmacy technician programs are experiencing important transitions to new educational standards, an enhanced accreditation framework, and changing requirements by state boards of pharmacy. The requirements are highly variable from state to state and have practical consequences for the pharmacy workforce in terms of technician recruitment, retention, and satisfaction. Using the state of Maryland as a case report, the purpose of this analysis was to compare the requirements necessary to become either a pharmacy technician or another type of health technologist, including board licensure or registration; training, education or certification or both; and 2016 median salary as reported by the Bureau of Labor Statistics. This analysis of salaries and job requirements for health technologists and technicians in the state of Maryland was conducted using the Standard Occupational Classification system and the Bureau of Labor Statistics wage data. Nuclear medicine technologists have the highest median salary at $38.50 per hour. No relationship between increasing entry-level qualifications and salary was identified, but pharmacy technicians were found to have the lowest median salary at $15.10 per hour. Although 5 occupations have median salaries greater than $30, 9 have median hourly salaries less than $20, of which 5 have minimum qualifications mandated by statute and regulation. Pharmacy technicians have the lowest median salary compared with other health technologists and technicians in Maryland. With pharmacy technicians reporting low satisfaction with salary as a reason for intending to leave an employer, implementing mandatory minimum entry-level requirements without a corresponding increase in salary could lead to a reduction in applicants for positions.


Inhibitory Effect of 5-Aminoimidazole-4-Carbohydrazonamides Derivatives Against Candida spp. Biofilm on Nanohydroxyapatite Substrate.
Candida can adhere and form biofilm on biomaterials commonly used in medical devices which is a key attribute that enhances its ability to cause infections in humans. Furthermore, biomaterial-related infections represent a major therapeutic challenge since Candida biofilms are implicated in antifungal therapies failure. The goals of the present work were to investigate the effect of three 5-aminoimidazole-4-carbohydrazonamides, namely (Z)-5-amino-1-methyl-N'-aryl-1H-imidazole-4-carbohydrazonamides [aryl = phenyl (1a), 4-fluorophenyl (1b), 3-fluorophenyl (1c)], on Candida albicans and Candida krusei biofilm on nanohydroxyapatite substrate, a well-known bioactive ceramic material. To address these goals, both quantitative methods (by cultivable cell numbers) and qualitative evaluation (by scanning electron microscopy) were used. Compounds cytocompatibility towards osteoblast-like cells was also evaluated after 24 h of exposure, through resazurin assay. The three tested compounds displayed a strong inhibitory effect on biofilm development of both Candida species as potent in vitro activity against C. albicans sessile cells. Regarding cytocompatibility, a concentration-dependent effect was observed. Together, these findings indicated that the potent activity of imidazole derivatives on Candida spp. biofilms on nanohydroxyapatite substrate, in particular compound 1c, is worth further investigating.


Race and Sex Differences in QRS Interval and Associated Outcome Among Patients with Left Ventricular Systolic Dysfunction.
Prolonged QRS duration is associated with increased mortality among heart failure patients, but race or sex differences in QRS duration and associated effect on outcomes are unknown. We investigated QRS duration and morphology among 2463 black and white patients with heart failure and left ventricular ejection fraction ≤35% who underwent coronary angiography and 12-lead electrocardiography at Duke University Hospital from 1995 through 2011. We used multivariable Cox regression models to assess the relationship between QRS duration and all-cause mortality and investigate race-QRS and sex-QRS duration interaction. Median QRS duration was 105 ms (interquartile range [IQR], 92-132) with variation by race and sex (P<0.001). QRS duration was longest in white men (111 ms; IQR, 98-139) followed by white women (108 ms; IQR, 92-140), black men (100 ms; IQR, 91-120), and black women (94 ms; IQR, 86-118). Left bundle branch block was more common in women than men (24% vs 14%) and in white (21%) versus black individuals (12%). In black patients, there was a 16% increase in risk of mortality for every 10 ms increase in QRS duration up to 112 ms (hazard ratio, 1.16; 95% CI, 1.07, 1.25) that was not present among white patients (interaction, P=0.06). Black individuals with heart failure had a shorter QRS duration and more often had non-left bundle branch block morphology than white patients. Women had left bundle branch block more commonly than men. Among black patients, modest QRS prolongation was associated with increased mortality.


Magnetic resonance imaging of osteoarticular infections in children.
Magnetic resonance imaging has become a common tool for the diagnosis and management of osteoarticular infections in children. We retrospectively review the MRI findings in 57 children (age range 4 months to 16 years; mean 6.3 years) diagnosed with osteoarticular infection. Thirty-eight cases were osteomyelitis, 4 were septic arthritis, 6 were spondylodiscitis, 7 were soft-tissue infections, 2 were pyomyositis, and 2 were chronic multifocal osteomyelitis. The pathogenesis and classification of osteoarticular infections are briefly discussed. Currently available imaging techniques are reviewed, and advantages and disadvantages are discussed. Magnetic resonance imaging indications and findings are shown. The most adequate magnetic resonance imaging sequences, as well as the usefulness of intravenous contrast material, are stressed.


Confinement of atomically defined metal halide sheets in a metal-organic framework.
The size-dependent and shape-dependent characteristics that distinguish nanoscale materials from bulk solids arise from constraining the dimensionality of an inorganic structure1-3. As a consequence, many studies have focused on rationally shaping these materials to influence and enhance their optical, electronic, magnetic and catalytic properties4-6. Although a select number of stable clusters can typically be synthesized within the nanoscale regime for a specific composition, isolating clusters of a predetermined size and shape remains a challenge, especially for those derived from two-dimensional materials. Here we realize a multidentate coordination environment in a metal-organic framework to stabilize discrete inorganic clusters within a porous crystalline support. We show confined growth of atomically defined nickel(II) bromide, nickel(II) chloride, cobalt(II) chloride and iron(II) chloride sheets through the peripheral coordination of six chelating bipyridine linkers. Notably, confinement within the framework defines the structure and composition of these sheets and facilitates their precise characterization by crystallography. Each metal(II) halide sheet represents a fragment excised from a single layer of the bulk solid structure, and structures obtained at different precursor loadings enable observation of successive stages of sheet assembly. Finally, the isolated sheets exhibit magnetic behaviours distinct from those of the bulk metal halides, including the isolation of ferromagnetically coupled large-spin ground states through the elimination of long-range, interlayer magnetic ordering. Overall, these results demonstrate that the pore environment of a metal-organic framework can be designed to afford precise control over the size, structure and spatial arrangement of inorganic clusters.


Compounds that increase or mimic cyclic adenosine monophosphate enhance tristetraprolin degradation in lipopolysaccharide-treated murine j774 macrophages.
Tristetraprolin (TTP) is a trans-acting factor that can regulate mRNA stability by binding to the cis-acting AU-rich element (ARE) in the 3'-untranslated region in mRNAs of certain transiently expressed genes. The best-studied target of TTP is tumor necrosis factor (TNF)-. By binding to ARE, TTP increases the degradation of TNF-alpha mRNA, thereby reducing the expression of TNF-alpha. We examined the effects of cAMP analogs and the cAMP-elevating agents forskolin and beta2-agonists on lipopolysaccharide (LPS)-induced TTP mRNA and protein expression by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blotting in activated macrophages. All of these agents caused a slight increase in LPS-induced expression of TTP mRNA. However, TTP protein levels were significantly reduced when the cells were treated with the combination of LPS and cAMP-elevating agent compared with LPS alone. Proteasome inhibitors MG132 (N-[(phenylmethoxy)-carbonyl]-L-leucyl-N-[(1S)-1-formyl-3-methylbutyl]-L-leucinamide) and lactacystin increased TTP protein levels and abolished the effects of cAMP-enhancing compounds on TTP protein levels. The results suggest that mediators and drugs that enhance intracellular cAMP reduce TTP expression in macrophages exposed to inflammatory stimuli by increasing TTP degradation through the proteasome pathway.


A light microscopic and immunohistochemical evaluation of scars.
Scars are commonly encountered by dermatopathologists and usually do not present a diagnostic challenge. However, in some cases, the pathologist may need to consider a broad differential diagnosis including fibrohistiocytic tumors, smooth muscle tumors, myofibroblastic proliferations and desmoplastic malignant melanoma. Although specific histologic aspects of scars have been well studied, a complete histochemical profile of scars, especially at various stages of evolution, has not been described. Twenty-five cases of scars including 8 normal scars, 5 hypertrophic scars and 12 keloids were studied. Sections were examined with Verhoeff van Giesson, colloidal iron, Giemsa, smooth muscle actin (SMA), CD34, Factor XIIIa and S-100. All scars were negative for CD34 expression. Factor XIIIa immunostaining identified only rare dermal dendrocytes. S-100 was absent in 23 of 25 cases and stained scattered cells (less than 10%) in the other 2 cases. SMA was positive in 14 of 25 cases with 6 of these showing staining of up to 50% of spindled cells. Elastic fibers were markedly reduced or absent in all cases, mucin showed moderate or marked staining in three-fourths of the cases and dermal mast cells showed a moderate increase in 5 cases. These findings confirm prior reports that negative staining with CD34, Factor XIIIa and S-100 can help differentiate scars from dermatofibrosarcoma protuberans, dermatofibroma and desmoplastic malignant melanoma, respectively. SMA staining is much more variable and requires careful interpretation.


Immunoelectron microscopic localization of the S19 site on the 30 S ribosomal subunit which is crosslinked to A site bound transfer RNA.
Phe-tRNA of Escherichia coli, specifically derivatized at the S4U8 position with the 9 A long p-azidophenacyl photoaffinity probe, was crosslinked exclusively to protein S19 of the 30 S ribosomal subunit when the transfer RNA occupied the ribosomal A site (Lin et al., 1983). Two antigenic sites for S19 are known, on opposite sides of the head of the subunit. In this work, discrimination between these two sites was accomplished by affinity immunoelectron microscopy. A dinitrophenyl group was placed on the acp3U47 residue of the same tRNA molecules bearing the photoprobe on S4U8. Addition of this group affected neither aminoacylation, A site binding, nor crosslinking. It also made possible specific affinity purification of crosslinked tRNA-30 S complexes from unreactive 30 S. Reaction of the 2,4-dinitrophenyl-labeled tRNA-30 S complex with antibody was followed by immunoelectron microscopy to reveal the sites of attachment. All of the bound antibody was associated with the ribosome region corresponding to only one of the two known antigenic sites for S19, namely the one closer to the large side projection of the 30 S subunit. A site within this region must be within 10 A of the S4U8 residue of tRNA when it is bound in the ribosomal A site.


Nitric oxide represses photosystem II and NDH-1 in the cyanobacterium Synechocystis sp. PCC 6803.
Photosynthetic electron transfer comprises a series of light-induced redox reactions catalysed by multiprotein machinery in the thylakoid. These protein complexes possess cofactors susceptible to redox modifications by reactive small molecules. The gaseous radical nitric oxide (NO), a key signalling molecule in green algae and plants, has earlier been shown to bind to Photosystem (PS) II and obstruct electron transfer in plants. The effects of NO on cyanobacterial bioenergetics however, have long remained obscure. In this study, we exposed the model cyanobacterium Synechocystis sp. PCC 6803 to NO under anoxic conditions and followed changes in whole-cell fluorescence and oxidoreduction of P700 in vivo. Our results demonstrate that NO blocks photosynthetic electron transfer in cells by repressing PSII, PSI, and likely the NDH dehydrogenase-like complex 1 (NDH-1). We propose that iron‑sulfur clusters of NDH-1 complex may be affected by NO to such an extent that ferredoxin-derived electron injection to the plastoquinone pool, and thus cyclic electron transfer, may be inhibited. These findings reveal the profound effects of NO on Synechocystis cells and demonstrate the importance of controlled NO homeostasis in cyanobacteria.


Rapid prototyping of PDMS devices using SU-8 lithography.
This protocol describes the fabrication of single and multi-layer SU-8 microstructures for generating microfluidic devices via PDMS (polymethyldisiloxane) casting. SU-8 is a negative, thick-film, epoxy based photoresist that has become widespread in the MEMS industry for producing durable, high aspect ratio microstructures for a variety of applications. It has become especially popular with microfluidics researchers to produce molds for PDMS casting since such molds allow for the rapid replication of prototype microfluidic structures made from PDMS. Although SU-8 processing does allow for rapid and straightforward development of devices it is prone to numerous pitfalls which have gained it a reputation of being somewhat of a "black art." This protocol attempts to give as full an account as possible of all the tricks and tips the author has learned over the years for processing SU-8. It also describes the casting of PDMS and plasma bonding for the generation of complete microfluidic devices ready for use in the lab.


Phase I clinical trial and pharmacokinetic evaluation of 4'-0-tetrahydropyranyladriamycin (THP-adriamycin).
Tetrahydropyranyladriamycin (THP-adriamycin) is an anthracycline analogue currently under development in Europe and Japan. Preclinical studies suggest that it may have greater activity and less cardiac toxicity than doxorubicin. We conducted a phase I clinical and pharmacologic study of THP-adriamycin given as a weekly 15-min infusion for 3 weeks, followed by 1 week of observation. Therapy was associated with minimal acute toxicity. The dose-limiting toxicity was neutropenia, usually maximal during the 4th week after treatment; alopecia was rare. The maximum tolerated dose was 25 mg/m2; for phase II studies using this schedule, a dose of 20 mg/m2 weekly for 3 weeks is recommended. Pharmacokinetic studies revealed a triphasic elimination of the parent compound with alpha, beta, and gamma half-lives of 5.6 min, 1.4 h, and 9.3 h, respectively. THP-adriamycin was rapidly taken up by blood cell components, with concentrations in red blood cells (RBCs), lymphocytes, and polymorphonuclear cells exceeding those in plasma. In all, less than 10% of the compound was eliminated in the urine within 24 h.


Prognostic value of plasma D-dimer levels in patients with small-cell lung cancer.
Little data exists with respect to the relationship between the level of plasma D-dimer and prognosis of small cell lung cancer (SCLC).The aim of this study was to investigate whether the levels of plasma D-dimer could be served as a prognostic factor in patients with SCLC. A total of 393 patients with SCLC were addressed in the present retrospective study. Plasma D-dimer levels were measured by immunoturbidimetric assay. The correlation between plasma D-dimer levels and other clinical features, progression free survival (PFS) and overall survival (OS) was analyzed statistically. The plasma D-dimer levels were significantly correlated with karnofsky performance status (KPS), tumor stage, number of metastatic sites, and treatment response. The PFS and OS of patients with elevated D-dimer levels before chemotherapy were significantly shorter than that of patients with normal D-dimer levels (PFS: 6.2 months versus 9.6 months, P<0.001; OS: 15.7 months versus 24.4 months, P<0.001). The patients with D-dimer levels converting from high to normal had better PFS and OS than those with D-dimer levels remaining high after two cycles of chemotherapy. According to multivariate analysis, elevated D-dimer level was confirmed to be an independent prognostic factor for worse survival. Elevated plasma D-dimer level could be served as an independent determinant of poor prognosis in patients with SCLC.


A novel approach used outcome distribution curves to estimate the population-level impact of a public health intervention.
To provide an analytical framework within which public health interventions can be evaluated, present its mathematical proof, and demonstrate its use using real trial data. This article describes a method to assess population-level effects by describing change using the distribution curve. The area between the two overlapping distribution curves at baseline and follow-up represents the impact of the intervention, that is, the proportion of the target population that benefited from the intervention. Using trial data from a parenting program, empirical proof of the idea is demonstrated on a measure of behavioral problems in 355 preschoolers using the Gaussian distribution curve. The intervention group had a 12% [9%-17%] health gain, whereas the control group had 3% [1%-7%]. In addition, for the subgroup of parents with lower education, the intervention produced a 15% [6%-25%] improvement, whereas for the group of parents with higher education the net health gain was 6% [4%-16%]. It is possible to calculate the impact of public health interventions by using the distribution curve of a variable, which requires knowing the distribution function. The method can be used to assess the differential impact of population interventions and their potential to improve health inequities.


(+/-)-3,4-Dihydroxy-8,9-methylenedioxypterocarpan and derivatives: cytotoxic effect on human leukemia cell lines.
Naturally occurring pterocarpans 1a,b, pterocarpan 1c, isoflavane 2 and ortho-quinone 3 were synthesized in the racemic form and their cytotoxic effect was evaluated on the human leukemia cell lines K562 (resistant to oxidative stress), Lucena-1 (MDR phenotype) and HL-60. Ortho-quinone 3 (IC(50)=1.5 microM, 1.8 microM and 0.2 microM, respectively) and catechol pterocarpan 1a (IC(50)=3.0 microM, 3.7 microM and 2.1 microM, respectively) were the most active compounds on these cells and were also evaluated on other human leukemia cell lines (Jurkat and Daudi). Ortho-quinone 3 was 2 to 10 times more potent than pterocarpan 1a, depending on the cell line considered, however, showed a greater toxicity for lymphocytes activated by PHA.


Antioxidative parameters in the seedlings of pigeonpea (Cajanus cajan (L.) Millspaugh) in response to Zn and Ni stresses.
The zinc (Zn) and nickel (Ni) as oxidative stress factors and associated responses of 6-day-old seedlings of two pigeonpea (Cajanus cajan (L.) Millspaugh) cultivars namely LRG30 and ICPL87 were studied. Zinc and Ni exposure increased lipid peroxidation in relation to their concentration. Reduction in dry matter accumulation of roots and shoots was noticed in Zn and Ni treatments. The activities of antioxidative enzymes such as superoxide dismutase, peroxidase and glutathione reductase registered higher values and the activity of catalase and the antioxidative substances such as ascorbic acid and total glutathione contents registered lower values in all the Zn and Ni treatments when compared to their controls. The levels of catalase, peroxidase and glutathione reductase and ascorbic acid and total glutathione contents were high in cv. LRG30 than in cv. ICPL87 in response to Zn and Ni treatments. However, the activity of superoxide dismutase, the major scavenger of O(2)(&z.rad;-) radical registered higher values in cv. ICPL87. The cv. LRG30 is less sensitive to Zn and Ni treatments compared to the cv. ICPL87. Correlation coefficients between the different antioxidant parameters and metal dose level, or dry matter accumulation, were established, assessing for an induced-oxidative stress. Additional evidence was provided by comparing the sensitivity of the two cultivars.


Evaluation of a rapid diagnostic test for measles IgM detection; accuracy and the reliability of visual reading using sera from the measles surveillance programme in Brazil, 2015.
Laboratory-based case confirmation is an integral part of measles surveillance programmes; however, logistical constraints can delay response. Use of RDTs during initial patient contact could enhance surveillance by real-time case confirmation and accelerating public health response. Here, we evaluate performance of a novel measles IgM RDT and assess accuracy of visual interpretation using a representative collection of 125 sera from the Brazilian measles surveillance programme. RDT results were interpreted visually by a panel of six independent observers, the consensus of three observers and by relative reflectance measurements using an ESEQuant Reader. Compared to the Siemens anti-measles IgM EIA, sensitivity and specificity of the RDT were 94.9% (74/78, 87.4-98.6%) and 95.7% (45/47, 85.5-99.5%) for consensus visual results, and 93.6% (73/78, 85.7-97.9%) and 95.7% (45/47, 85.5-99.5%), for ESEQuant measurement, respectively. Observer agreement, determined by comparison between individuals and visual consensus results, and between individuals and ESEQuant measurements, achieved average kappa scores of 0.97 and 0.93 respectively. The RDT has the sensitivity and specificity required of a field-based test for measles diagnosis, and high kappa scores indicate this can be accomplished accurately by visual interpretation alone. Detailed studies are needed to establish its role within the global measles control programme.


The role of school enjoyment and connectedness in the association between depressive and externalising symptoms and academic attainment: Findings from a UK prospective cohort study.
Previous research on the relationship between children's depressive and externalising symptoms, experience of school, and academic attainment is inconclusive. The aims of this study were (i) to test bidirectional associations between children's school experience and depressive and externalising symptoms at age 10-11 and 13-14, (ii) to ascertain whether school experience age 13-14 is associated with academic attainment age 16, and (iii) to test whether school experience mediates the relationship between depressive or externalising symptoms and attainment. Data was used from the Avon Longitudinal Study of Parents and Children (n=6,409). A cross-lagged model was used to investigate bidirectional associations between school experience (enjoyment and connectedness) and depression and externalising at age 10-11 and 13-14. The same framework was used to test if school experience aged 13-14 mediated associations of depressive and externalising symptoms with later attainment. Depressive and externalising symptoms at 10-11 were negatively associated with school connectedness (depressive: standardised β=-0.06, CI: -0.11, 0.01; externalizing: β=-0.13, CI: -0.17, -0.08), and school enjoyment at 13-14 (depressive β=-0.04, -0.08, 0.03; externalising: β=-0.08, CI: -0.13, -0.03). School enjoyment at 13-14 was positively associated with attainment at 16 (β=0.10, CI: 0.04, 0.15), and partially mediated associations between depressive and externalising symptoms at 10-11 and attainment at 16 (depressive: proportion mediated 2.2%, CI: -1.5, 5.9; externalising: proportion mediated; 4.7%, CI: 0.7, 10.1,). Results may be subject to residual confounding. School enjoyment is a potentially modifiable risk factor that may affect educational attainment of adolescents with depressive or externalising symptoms.


A Fokker-Planck equation for growing cell populations.
Closed form solutions are obtained for a Fokker-Planck model for cell growth as a function of maturation velocity and degree of maturation. For reproduction rules where daughter cells inherit their parent's maturation velocity the complete solution is derived in terms of Airy functions. For more complicated reproduction rules partial results are obtained. Emphasis is given to the relationship of these problems to time dependent linear transport theory.


Flex-Array® - a novel multi-well vessel system for the immobilization and multi-modal testing of intact formalin-fixed paraffin-embedded (FFPE) cells or tissues.
Flex-Array® is a novel multi-well system that extends the key features of current high-performance microscope slides used in advanced staining techniques. The Flex-Array® system facilitates the immobilization of FFPE cell or tissue sections onto a multi-well array for the subsequent performance of single analyte (IHC) or multiplexed immunohistochemistry (MIHC). Additionally, the Flex-Array® device is compatible with fluorescent and colorimetric in situ hybridization (FISH) and adds new capabilities such as replicate analysis, quantitative ELISA-like assays and microdissection-free nucleic acid extraction. The Flex-Array® facilitates rapid, contextually rich and high-precision multi-modal analysis of FFPE cells and tissues at a significant reduction in testing, data acquisition and analysis costs.


Retracted: Innovation of Ideological and Political Education Management of College Students Based on IOT Big Data Technology in a Wireless Network Environment.
[This retracts the article DOI: 10.1155/2022/9585760.].


A signal-to-noise-ratio-based analysis of multifocal visual-evoked potentials in multiple sclerosis risk assessment.
To study the value of using the signal-to-noise ratio (SNR) of multifocal visual-evoked potentials (mfVEPs) in assessment of subjects at risk of developing multiple sclerosis (MS). MfVEP signals were obtained from 15 patients with radiologically isolated syndrome (RIS), from 28 patients with clinically isolated syndrome (CIS), from 28 with clinically definite MS and from 24 control subjects. The CIS and MS groups were divided into two subgroups: those with eyes affected by optic neuritis (ON) and those without (non-ON). The mfVEPs' SNR was obtained for both the whole visual field and at various eccentric rings. The area under the curve (AUC) was calculated by comparing the control subjects' mfVEP SNR values with those of the RIS, CIS and MS groups. In whole visual field analysis, risk of developing MS increased as SNR decreased (SNRCONTROL=0.70, SNRRIS=0.62, SNRCIS-nonON=0.54, SNRCIS-ON=0.40, SNRMS-nonON=0.52, SNRMS-ON=0.40). Ring 5 (9.8°-15° eccentricity) was most affected by the SNR decrease, as indicated by its higher AUC values (AUCFULL_EYE=0.81, AUCRING_5=0.89). A significant relationship (Spearman correlation, ρRING_5=0.61) between SNR values and disability severity on the Expanded Disability Status Scale (EDSS) was observed in clinically definite MS patients. A new method based on analysis of the SNR of mfVEP signal amplitude improves assessment of patients at risk of developing MS. Improved mfVEP assessment of MS-risk patients was achieved by using SNR values at 9.8°-15° eccentricity of the visual field.


Association of genetic variability in selected regions in visfatin (NAMPT) gene with anthropometric parameters and dietary composition in obese and non-obese Central-European population.
Visfatin (NAMPT/PBEF) is a recently identified adipocytokine which harbors strong insulin-mimetic activity and was reported to be associated with obesity. However, nothing is known about whether visfatin is related to specific nutritional behavior which may result in obesity development. This is the first study focusing on genetic variability of the visfatin gene and its association with circulating visfatin, anthropometric parameters and dietary composition. We analyzed a total of 11 exons and adjacent non-coding regions of the NAMPT gene in 20 extremely obese Czech individuals (mean BMI 52.2±5.0 SD) using direct sequencing and a frequency of rs2302559 was established in the validation cohort of another 605 individuals with completed 7-day food records and complex anthropometric measurements. Serum levels of visfatin, leptin and leptin-receptor were measured in all sequenced individuals and in part of the validation cohort. Three common polymorphisms were identified, two in non-coding regions (rs78411774 A/C, rs71564769 A/C) and one synonymous SNP in exon 7 (rs2302559 A/G). The rs2302559 showed significant correlation with visfatin serum level throughout the entire study cohort (p<0.001); there was a significant tendency toward higher visfatin levels in G allele carriers with GG homozygotes having the highest visfatin serum levels. Furthermore, a negative correlation was observed between visfatin and leptin serum level (p=0.01). No association between investigated SNPs and anthropometric parameters or native dietary composition was observed. This is the first study to demonstrate that the rs2302559 polymorphism in the PBEF gene is related to circulating levels of visfatin. As the SNP is synonymous, we hypothesize it might be linked to another SNP in the PBEF gene which controls visfatin serum levels.


Exploration of the testis in infertile men. Relationships among serum levels of FSH, LH, 17-alpha-OH-progesterone and testosterone.
A considerable body of evidence is available indicating a paracrine relationship between the seminiferous tubules and the Leydig cells. In 113 adult subjects in basal conditions the blood levels were determined of FSH (follicle stimulating hormone), LH (luteinizing hormone), 17-alpha-OH-P (17-alpha-OH-progesterone) and T (testosterone) either as a whole or as a free fraction. According to the sperm counts and the FSH levels, the studied subjects were divided into three groups: a group N (Normozoospermia) with sperm counts greater than 20 million/ml and FSH levels of 2.5 +/- 1.5 (mean +/- SD, mIU/ml), a group MO (moderate oligozoospermia) with mild degree of oligozoospermia (5-10 mill) and FSH levels in the range found in group N, a group SO (severe oligozoospermia) with severe degree of oligozoospermia (sperm count less than 5 mill/ml) and FSH levels greater than 2 SD the mean value in the N. Serum levels of LH, 17-alpha-OHP, total T, free T and FSH/LH, LH/T, 17-alpha-OHP/T ratios in group MO and SO were compared with those found in the group N.(ABSTRACT TRUNCATED AT 250 WORDS)


Childhood giant pituicytoma: a report and review of the literature.
Pituicytoma is a rare, benign, primary tumour, almost all of which occur in adults. Here, we present one case of giant pituicytoma in a boy and a review literature to assist in understanding its natural history, behaviour, clinicopathological features and treatment options. A PUBMED search using the keywords "pituicytoma" was performed, and the citations were reviewed. We found 65 cases of pituicytomas, including our report, in the international literature to date; among these cases, only three were diagnosed in patients under 14 years old. Pituicytoma is a slow-growing, rare, low-grade glial neoplasm that originates in the neurohypophysis. Currently, the optimal treatment is gross total resection, and confirmed diagnosis relies upon pathological tests. Regular MRI follow-up is recommended.


Matching-to-sample by pigeons: the dissociation of comparison choice frequency from the probability of reinforcement.
It has been proposed that comparison choice in matching-to-sample should depend on two factors, the relative probability of reinforcement associated with each of the comparison stimuli and the conditional probability of each comparison stimulus being correct given presentation of one of the samples. DiGian and Zentall [DiGian, K.A., Zentall, T.R., 2007. Matching-to-sample in pigeons: in the absence of sample memory, sample frequency is a better predictor of comparison choice than the probability of reinforcement for comparison choice. Learn Behav. 35, 242-261] have shown that sample frequency together with the probability of choosing each of the comparison stimuli in training can influence comparison choice when delays are introduced, when the number of reinforcements associated with each of the comparison stimuli is equated. Furthermore, Zentall and Clement [Zentall, T.R., Clement, T.S., 2002. Memory mechanisms in pigeons: Evidence of base-rate neglect. J. Exp. Psych.: Anim. Behav. Proc. 28, 111-115] have found that sample frequency can affect comparison choice when delays are introduced independently of the number of choices of each of the comparison stimuli in training and the number of reinforcements associated with each of the comparison stimuli is equated. In the present experiment we found that the probability of choosing each of the comparison stimuli in training can affect comparison choice when delays are introduced, independently of sample frequency and when the number of reinforcements associated with each of the comparison stimuli is equated. Together, these experiments suggest that when the sample is not available, there is a partial dissociation between comparison choice and the probability of reinforcement associated with each of the comparison stimuli.


APJ Regulates Parallel Alignment of Arteries and Veins in the Skin.
Molecular pathways regulating the development of arterial and venous endothelial cells (ECs) are now well established, but control of parallel arterial-venous alignment is unclear. Here we report that arterial-venous alignment in the skin is determined by apelin receptor (APJ) expression in venous ECs. One of the activators of APJ is apelin. We found that apelin is produced by arterial ECs during embryogenesis, induces chemotaxis of venous ECs, and promotes the production of secreted Frizzled-related protein 1 (sFRP1) by APJ(+) ECs. sFRP1 stimulates matrix metalloproteinase production by Ly6B.2(+) neutrophil-like cells located between the arteries and veins, resulting in remodeling of extracellular matrices to support venous displacement. Moreover, using apelin- or APJ-deficient mice, which exhibit arterial-venous disorganization, we found that arterial-venous alignment is involved in thermoregulation, possibly by regulating countercurrent heat exchange. We hypothesize that the evolution of parallel juxtapositional arterial-venous alignment was an adaptation to reduce body heat loss.


Ultrastructural immunocytochemistry of gonadotrophs in the goldfish pituitary gland.
The immunocytochemical distribution of gonadotropin (GTH) in the goldfish pituitary gland was studied applying the peroxidase-antiperoxidase (PAP) method and the protein A-gold technique at light- and electron-microscopic levels, respectively, with an antiserum raised against silver carp GTH. In the light-microscopic immunocytochemistry, PAS-positive cells in the proximal pars distalis showed strong reaction with the antiserum. Gold particles wee concentrated both on globules (large) and on granules (small) of the gonadotrophs (PAS-positive cells) in the electron-microscopic immunocytochemistry. Other cells in the pituitary gland, including thyrotrophs, displayed no immunoreactivity with the antiserum at the dilutions tested. These results indicate, not only immunocytochemical distribution of GTH both in globules and in granules in the gonadotrophs, but also the high purity of the antigen (silver carp GTH) and specificity of the antiserum.


Increased urinary 1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine excretion in thalassemia patients: markers for lipid peroxidation-induced DNA damage.
Thalassemic diseases including homozygous beta-thalassemia and beta-thalassemia/Hb E (beta-Thal/Hb E) are prevalent in Southeast Asia. Iron overload is a common complication in beta-thalassemia patients which induces intracellular oxidative stress and lipid peroxidation (LPO). LPO end products generate miscoding etheno adducts in DNA which after their repair are excreted in urine. We investigated whether urinary levels of 1,N6-ethenodeoxyadenosine (epsilondA) and 3,N4-ethenodeoxycytidine (epsilondC) can serve as putative cancer risk markers in beta-Thal/Hb E patients. epsilondA and epsilondC levels were assayed in collected urine samples by immunoprecipitation-HPLC-fluorescence and 32P-postlabeling TLC, respectively. Mean epsilondA (fmol/micromol creatinine) levels in urine of beta-Thal/Hb E patients ranged from 4.8 to 120.4 (33.8+/-3.9; n=37) and were 8.7 times higher compared to asymptomatic controls (1.4-13.8; 3.9+/-0.8; n=20). The respective epsilondC levels ranged from 0.15 to 32.5 (5.2+/-1.3; n=37) and were increased some 13 times over controls (0.04-1.2; 0.4+/-0.7; n=20). epsilondC levels were correlated positively with NTBI (r=0.517; P=0.002), whereas epsilondA showed only a trend (r=0.257; P=0.124). We conclude that the strongly increased urinary excretion of etheno adducts indicates elevated LPO-induced DNA damage in internal organs such as the liver. These highly promutagenic lesions may contribute to the increased risk of thalassemia patients to develop hepatocellular carcinoma.


Geographic distribution and community structure of bumblebees in the northern Iberian peninsula.
Relationships between species distribution and abundance, the influence of proboscis length on species-packing, and species associations within the local assemblages were studied in local communities of bumblebees in northern Spain along an altitudinal gradient. Local species abundance and altitudinal range occupied accounted for much of the variation in species distribution. Altitudinal range occupied by species was related to species distribution, but the most important variable accounting for species distribution was the local percentage abundance. Despite this, there was no evidence for age abundance. Despite this, there was no evidence for bimodality in the distributions of species incidence. A general trends for mean proboscis length in each locality to be greater in lowland localities exists, but this variable was not related to species distribution or abundance. Proboscis length spacings were studied among species in local assemblages and in most of the cases observed spacing did not differ from random expectations. The same patterns were demonstrated calculating spacings for 'core' species in each local assemblage. Furthermore, species showed little tendency towards associations, so it may be concluded that bumblebee assemblages were irregularly structured and no clear patterns emerged from the present study.


Sustained response following BTK inhibitors based treatment in HIV-related primary central nervous system lymphoma: case report.
Despite increasing effort for treating primary central nervous system lymphoma (PCNSL), the prognosis of human immunodeficiency virus (HIV) -related PCNSL was still unsatisfactory. There is currently a lack of clinical evidence for the application of Bruton tyrosine kinase (BTK) inhibitor in HIV-related PCNSL. We reported two HIV-related PCNSL patients, who achieved sustained remission by application of BTK inhibitor based treatment. This protocol had not been previously reported for the treatment of HIV-related PCNSL. The two cases were characterized by the treatment choice of Bruton tyrosine kinase (BTK) inhibitor. Rituximab was not recommended for them due to their very low CD4+ T cell counts. They both took MTX as the first-line therapy and got a relief in initial phase. For the first case, ibrutinib was kept both in the first-line therapy and in the maintenance therapy. When the second case underwent a progressive disease, we continued to use orelabrutinib as one of the salvage treatment, in combination with programmed cell death-1 (PD-1) inhibitor plus lenalidomide. They both achieved a continuous response of up to 20 months without opportunistic infection. This report highlights the safety and effectiveness of BTK inhibitors, as well as lenalidomide and PD-1 inhibitor in HIV-related PCNSL patients. Both the new therapeutic approaches and a multidisciplinary team authentically contributed to improved survival outcome among HIV-positive PCNSL patients.


Controlled release starch-lipid implant for the therapy of severe malaria.
Parenteral depot systems can provide a constant release of drugs over a few days to months. Poly-(lactic acid) (PLA) and Poly-(lactide-co-glycolide) (PLGA) are the most commonly used polymers in the production of these systems. Finding alternatives to these polymers is of great importance to avoid certain drawbacks of these polymers (e.g. microacidity) and to increase the selection possibilities. In this study, different types of starch in combination with glycerol monostearate (GMS) were developed and investigated for their physicochemical properties and release characteristics. The noninvasive method of electron paramagnetic resonance (EPR) was used to study the release kinetics and mechanisms of nitroxide model drugs. The studies demonstrated the general suitability of the system composed of high amylose starch and GMS to form a controlled release system. For further characterization of the prepared system, formulations with different proportions of starch and GMS, loaded with the antimalarial agents artesunate or artemether were prepared. The implants were characterized with X-ray powder diffraction (XRPD) and texture analysis. The in vitro release studies demonstrated the sustained release of artemether over 6 days from a starch-based implant which matches desired kinetic for the treatment of severe malaria. In summary, a starch-based implant with appropriate mechanical properties was produced that can be a potential candidate for the treatment of severe malaria.


Fragility fracture care gap at a tertiary teaching hospital in Malaysia.
Fracture begets fracture, pharmacological treatment is needed to prevent secondary fractures. This study found that there was a fragility fracture care gap where both bone health investigations and treatment initiation rates were low. Strategies such as Fracture Liaison Service is needed to address the care gap. This study aimed to investigate the clinical burden and secondary fracture prevention of fragility fractures at a tertiary teaching hospital in Malaysia. Electronic medical records of all patients admitted with fragility fractures between 1 January 2017-31 December 2018 were reviewed. Patients < 50 years old, with non-fragility fractures, restricted access to medical records, transferred to another hospital or who passed away during admission were excluded. Descriptive statistics were used to summarise patients' characteristics, frequency of fragility fractures, and secondary fracture prevention details. Binomial logistic regression was performed to analyse predictive factors for post-fracture bone health assessments and treatment initiation. 1030 patients [female (767/1030, 74.5%)] presented with 1071 fractures [hip fractures (378/1071, 35.3%)]. 170/993 (17.1%) patients were initiated on anti-osteoporosis medications (AOMs) and 148/984 (15.0%) had bone mineral density (BMD) performed within 1-year post-fracture. Less than half (42.4%) of the patients remained on treatment at 1-year post-fracture. Older patients [65-74 years old: odds ratio (OR) = 2.18, 95%CI 1.05-4.52, p = 0.04; ≥ 75 years: OR = 3.06, 95%CI 1.54-6.07, p < 0.01], hip fractures (OR = 1.95, 95%CI 1.23-3.11, p < 0.01), Chinese ethnicity (OR = 1.90, 95%CI 1.07-3.35, p = 0.03),previously diagnosed with osteoporosis (OR = 2.65, 95%CI:1.32-5.31, p < 0.01) and a BMD test performed (OR = 12.48, 95%CI 8.04-19.37, p < 0.01) were found to have higher AOM initiation. Patients with past diagnosis of osteoporosis (OR = 4.45, 95%CI 2.25-8.81, p < 0.01) and initiated on AOM (OR = 11.34, 95%CI 7.57-16.97, p < 0.01) had a higher likelihood to undergo BMD testing. The AOM initiation and BMD testing rates were low. There is a need to address the fragility fracture care gap with strategies such as Fracture Liaison Service.


Utility of the Oral Glucose Tolerance Test to Assess Glucose Abnormalities in Adolescents with Polycystic Ovary Syndrome.
The aim of this study was to examine the prevalence of and risk factors for abnormal glucose metabolism in a large population of adolescents with polycystic ovary syndrome (PCOS). DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A retrospective chart review was performed of 360 patients who presented to the pediatric gynecology outpatient clinic for evaluation of PCOS between January 2004 and May 2012. A total of 163 patients fulfilled criteria for a diagnosis of PCOS and had adequate clinical and laboratory data. Twenty-six adolescents (16.0%) had impaired glucose tolerance and 2 patients (1.2%) met criteria for a provisional diagnosis of type 2 diabetes. All 28 subjects with abnormal glucose metabolism were identified using the 2-hour plasma glucose of the oral glucose tolerance test. Conversely, the fasting glucose values only successfully detected 2 patients with hyperglycemia, both of whom also had abnormal 2-hour glucose levels. Adolescents with abnormal glucose metabolism were more likely to have reported a positive family history (P = .02) and had higher body mass index z scores (2.8 ± 1.1 vs 1.8 ± 1.2; P < .01). When patients were classified into normal weight (n = 29) and obese/overweight groups (n = 117), all of the patients with abnormal glucose metabolism were overweight or obese. In the largest series to date, we describe a prevalence of abnormal glucose metabolism in adolescent patients with PCOS of 17.2%. Abnormal glucose metabolism is associated with many of the known risk factors for metabolic syndrome. Our results support that the oral glucose tolerance test is a superior diagnostic test to assess abnormal glucose levels in overweight and obese adolescents but that this test might have limited utility in normal weight adolescents with PCOS.


Chronically homeless veterans with gambling disorder: Epidemiology, clinical correlates, and traumatic experiences.
Gambling disorder (GD) is often a concern for people living in poverty. Although GD has been correlated with homelessness, there has been no study of factors related to chronic homelessness among veterans with GD. This study used data from specialized homeless programs from the U.S. Department of Veterans Affairs Homeless Operations Management System to explore prevalence and correlates of chronic homelessness among veterans with GD in this program and to describe initial descriptive epidemiology. Chi-square tests, analyses of variance, and logistic regressions were conducted to examine differences in sociodemographic, military, clinical, and behavioral characteristics between veterans with versus without chronic homelessness. Of 6053 veterans with GD, 1733 (28.6%) had chronic homelessness. Veterans with versus without chronic homelessness were more likely to be older, male, unemployed, and of low educational attainment and report having spent fewer years in the military. Chronic homelessness was associated with elevated odds of mental health and medical diagnoses, traumatic experiences, incarceration, and suicidal thoughts. Veterans with versus without chronic homelessness more frequently reported needing substance use, medical and psychiatric treatments but expressed low interest in participation in psychiatric treatment. Veterans with GD and chronic homelessness have more clinical and behavioral concerns and needs for treatment, but participate in treatment at lower rates. It may be important to address both chronic homelessness and GD concurrently in order to effectively support veterans facing these challenges.


Ofloxacin induces cytoplasmic respiration-deficient mutants in yeast Saccharomyces cerevisiae.
Ofloxacin, a new quinolone with potent antibacterial activity, was also found to be effective against yeast. At relatively high concentrations, and at mild alkaline pH, ofloxacin inhibited the growth of yeast cells in medium containing glucose, and prevented growth on glycerol, as carbon and energy source. The cells growing in the presence of ofloxacin exhibited abberrantly budded forms, lost their viability and many of them converted to cytoplasmic respiration-deficient mutants. Induction of mutants was also observed under non-growing conditions. The petite clones analysed exhibited suppressiveness and contained different fragments of the wild-type mitochondrial genome.


Differential distribution of distinct forms of myeloperoxidase in different azurophilic granule subpopulations from human neutrophils.
Myeloperoxidase (MPO), a characteristic enzyme of human polymorphonuclear neutrophils (PMN), is localized in specialized lysosomal or azurophilic granules, and can be resolved into three distinct forms (I, II, III) by ion-exchange chromatography. Granules were isolated from single donor PMN and fractionated with centrifugation into two different azurophilic subpopulations (high and low density) by banding in a continuous sucrose density gradient. Ion-exchange chromatography of granule extracts indicated that the lower density granules contained mainly MPO forms II and III while the higher density granules appeared to contain all three forms, but in much reduced amounts. Sodium dodecylsulfate polyacrylamide gel electrophoresis showed that, the mobilities of the heavy subunits of MPO appeared to be inversely related to the density of the granule population from which they were extracted. These observations suggest that the different forms of MPO may have distinct functional roles and/or are a possible reflection of maturational differences among the granule subpopulations.


Detection and prediction of land cover changes using Markov chain model in semi-arid rangeland in western Iran.
The study of changes and destruction rate in the previous years as well as the possibility of prediction of these changes in the following years has a key role in optimal planning, controlling, and restricting non-normative changes in the future. This research was approached to detecting land use/cover changes (1985-2007) and to forecast the changes in the future (2021) use of multitemporal satellite imagery in semi-arid area in western Iran. A supervised classification of multilayer perceptron (MLP) was applied for detecting land use changes. The study area was classified into five classes, those of forest, rangeland, agriculture, residential, and barren lands. The change detection analysis indicated a decreasing trend in forest cover by 30.42%, while other land uses were increased during 1985 to 2007. The land use changes were predicted using Markov chain model for 2021. The model was calibrated by comparing the simulated map with the real detected classes of land cover in 2007. Then, for further model processing, an acceptable accuracy at 83% was achieved between them. Finally, land use changes were predicted by using transition matrix derived from calibrated approach. The findings of this study demonstrate a rapid change in land use/cover for the coming years. Transforming the forest into other land uses especially rangeland and cropland is the main land cover changes in the future. Therefore, the planning of protection and restoration of forest cover should be an essential program for decision-makers in the study area.


Retrospective detection of a subclinical hepatitis A virus (HAV) epidemic affecting juvenile cohorts of the Hungarian population.
Sero-epidemiological surveys of serum samples taken in 1982, 1987, 1994 and 1999 have been performed with hepatitis A virus-specific (HAV-specific) serological tests. Results obtained during these surveys show that the proportion of seropositive blood donors decreased from 69% to 18% within 17 years. The authors have recognised a (mainly subclinical) epidemic, affecting about 115000 teenagers in 1992-1994 in Hungary, is a threatening phenomenon. It was calculated that only about 3600 clinical diseases were associated with the epidemic, recognised retrospectively from the findings of the four sero-epidemiological surveys. Epidemiological data indicated that the excess clinical diseases caused by HAV concentrated in the southern counties of Hungary, which have been affected by the social and military activities between 1992 and 1994. Due to the decrease of subjects seropositive for HAV, sera from preselected or actively immunised donors will be required in the future and vaccination against HAV with killed virus is likely to be recommended for risk groups. Furthermore, health authorities might promote active immunisation of young children against HAV infection; for that, promotion of manufacturing combination vaccines of HAV/HBV/DPT or, for certain countries, HAV/DPT would be desirable.


Mitochondria, synaptic plasticity, and schizophrenia.
The conceptualization of schizophrenia as a disorder of connectivity, i.e., of neuronal?synaptic plasticity, suggests abnormal synaptic modeling and neuronal signaling, possibly as a consequence of flawed interactions with the environment, as at least a secondary mechanism underlying the pathophysiology of this disorder. Indeed, deficits in episodic memory and malfunction of hippocampal circuitry, as well as anomalies of axonal sprouting and synapse formation, are all suggestive of diminished neuronal plasticity in schizophrenia. Evidence supports a dysfunction of mitochondria in schizophrenia, including mitochondrial hypoplasia, and a dysfunction of the oxidative phosphorylation system, as well as altered mitochondrial-related gene expression. Mitochondrial dysfunction leads to alterations in ATP production and cytoplasmatic calcium concentrations, as well as reactive oxygen species and nitric oxide production. All of the latter processes have been well established as leading to altered synaptic strength or plasticity. Moreover, mitochondria have been shown to play a role in plasticity of neuronal polarity, and studies in the visual cortex show an association between mitochondria and synaptogenesis. Finally, mitochondrial gene upregulation has been observed following synaptic and neuronal activity. This review proposes that mitochondrial dysfunction in schizophrenia could cause, or arise from, anomalies in processes of plasticity in this disorder.


Immunodominant viral peptides as determinants of cross-reactivity in the immune system--Can we develop wide spectrum viral vaccines?
When we look back to Edward Jenner vaccination of a young man in 1796, we cannot help thinking that he was both lucky and crazy. Crazy because he decided to test in a human being a hypothesis based mainly in the traditional belief that people who had acquired cowpox from the udders of a cow were thereafter resistant to smallpox, a quite devastating disease, and lucky because (even considering that he did not know this at that time) he succeeded to induce protection against a pathogen through the induction of an immune response directed against a different agent. Not only was he able to protect the young man but he took the first step towards the development of a vast new field, vaccination. It is acceptable to say that Jenner was lucky because he succeeded in promoting protection against smallpox using a cowpox virus and this induction of protection in a cross-reactive way is believed to be quite rare. Nevertheless, more and more examples of cross-reactive immune responses are being described and we are beginning to admit that cross-reactivity is far more common and important than we used to think. Here we review cross-reactivity in the immune system and the plasticity of T cell recognition. Based on the existence of T cell receptor promiscuous recognition and cross-recognition of conserved viral immunodominant epitopes, we propose two approaches to develop wide spectrum viral vaccines. The first one is based on the identification, characterization, and cloning of immunodominant viral epitopes able to stimulate responses against different viruses. The produced peptides could then be purified and serve as a basis for vaccine therapies. A second strategy is based on the identification of conserved patterns in immunodominant viral peptides and the production of synthetic peptides containing the amino acid residues necessary for MHC anchoring and TCR contact. Although we are still far from a complete knowledge of the cross-reactivity phenomenon in the immune system, the analysis of immunodominant viral epitopes and the identification of particular "viral patterns" seems to be important steps towards the development of wide spectrum viral vaccines.


Enhanced degradation of Rhodamine B via α-Fe2O3 microspheres induced persulfate to generate reactive oxidizing species.
The porous α-Fe2O3 microspheres (MS-Fe2O3) were obtained through in-situ ion exchange-calcination method and then utilized to activate persulfate (PS) for Rhodamine B (Rh B) degradation. The influences of some important operational parameters were investigated for the MS-Fe2O3/PS system. Additionally, the physicochemical properties of the as-fabricated MS-Fe2O3 were revealed with the assistance of some analytical instruments (i.e., X-ray diffraction (XRD), scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectra (XPS), Brunauer-Emmett-Teller (BET) and vibrating sample magnetometer (VSM)). The results showed that the physicochemical properties of MS-Fe2O3 played an important role in the activation of PS, which promoted MS-Fe2O3 to effectively induce PS to generate reactive oxidizing species, thus Rh B could be nearly 100% degraded within 30 min under near-neutral pH solution. Noticeably, the as-prepared MS-Fe2O3 revealed magnetism and could be separated conveniently through external magnetic, which was beneficial to reuse the catalyst. Finally, the reactive oxidizing species (SO4- and OH) participating in the oxidation process were illustrated by electron paramagnetic resonance (EPR) and radical quenching studies, and then a rational mechanism was proposed to better understand the catalytic oxidation degradation of organic pollutants.


Follicle-stimulating hormone receptor polymorphism (Thr307Ala) is associated with variable ovarian response and ovarian hyperstimulation syndrome in Indian women.
To evaluate the association of FSH receptor polymorphism and ovarian response. Retrospective study. Academic research institute and private IVF clinic. Fifty women were recruited in an assisted reproductive technology program (ART) and 100 proven fertile women of Indian origin. Polymerase chain reaction, restriction fragment-length polymorphism for detecting polymorphisms at T(307)A and N(680)S. FSH receptor polymorphisms, serum FSH, and estradiol levels, amount of FSH administered, occurrence of ovarian hyperstimulation syndrome (OHSS). Prevalence of polymorphism at 307 position was 24%, 53%, and 23% in controls and 24%, 62%, and 14% in ART subjects for TT, TA, and AA, respectively, whereas at position 680, it was 31%, 56%, and 13% in controls and 42%, 46%, and 12% in ART subjects for NN, NS, and SS, respectively. The amount of FSH required for ovulation induction was low in AA compared with TT and TA subjects; the estradiol levels before and on the day of hCG administration were significantly higher. Eighty-five percent of the subjects with AA genotype developed OHSS. In Indian women, the subjects with AA genotype require low amounts of FSH for ovarian stimulation and have an increased risk of developing OHSS.


Physiological synchrony is associated with attraction in a blind date setting.
Humans are social animals whose well-being is shaped by the ability to attract and connect with one another, often through brief interactions. In addition to physical features, a choreography of movements, physical reactions and subtle expressions may help promote attraction. Here, we measured the physiological dynamics between pairs of participants during real-life dating interactions outside the laboratory. Participants wore eye-tracking glasses with embedded cameras and devices to measure physiological signals including heart rate and skin conductance. We found that overt signals such as smiles, laughter, eye gaze or the mimicry of those signals were not significantly associated with attraction. Instead, attraction was predicted by synchrony in heart rate and skin conductance between partners, which are covert, unconscious and difficult to regulate. Our findings suggest that interacting partners' attraction increases and decreases as their subconscious arousal levels rise and fall in synchrony.


[Lack of Collaboration, Lack of Staff or Disappearance of the Data: the Difficult Access to the Psychiatric Archives].
This paper presents the way we try to track the history of mental health services offered to residents of official language minority communities throughout Northern and Eastern Ontario. The study also holds an interest in the post-deinstitutionalization paths of patients suffering from mental health conditions. Our research strand concerns Northern Ontario, its patient associations, its services, its specialists and its institutions and the access to hospitals archives.


3D food printing: Controlling characteristics and improving technological effect during food processing.
3D printing technology has a wide range of application in the food industry. Current research has focused on the improving printing accuracy and expanding the range of printing materials, while the feasibility of 3D printing technology in controlling processing characteristics and improving technological aspects have not yet been critically reviewed. This paper provides a concise critical evaluation of techniques to enhance the characteristics of 3D printed foods including their post-processing e.g. drying, frying, baking, cooling, sterilization etc. This paper provides guidance for future research and development in the field of post-treatment of 3D food printed products which is critically important for wider industrial application of this rapidly evolving technology.


Extracorporeal shock wave enhanced extended skin flap tissue survival via increase of topical blood perfusion and associated with suppression of tissue pro-inflammation.
Distal skin flap ischemic necrosis is a significant challenge in reconstructive surgery. This study assessed whether extracorporeal shock wave (ESW) treatment rescues compromised flap tissue by enhancing tissue perfusion and is associated with suppression of inflammatory response. This study used the dorsal skin random flap model in a rodent. Thirty-six male Sprague Dawley rats were divided into three groups. Group I, a control group, received no treatment. Group II was administrated 500 impulses of ESW treatment at 0.15 mJ/mm(2) as a single treatment immediately postoperatively. Group III received 500 impulses of ESW at 0.15 mJ/mm(2) applied immediately postoperatively and the day following surgery. Flap blood perfusion was detected by laser Doppler. Flap survival/necrosis area and histological staining of flap ischemia zone was performed on day 7 postoperatively. The tumor necrosis factor alpha, vascular endothelial growth factor, and proliferating cell nuclear antigen expression were evaluated with immunohistochemical staining. Experimental results indicated that the necrotic area of the flaps in Group II was significantly reduced compared with that in the control group (13 +/- 2.6% versus 42 +/- 5.7%, P < 0.01). There was small and insignificant reduction in the necrotic area in Group III compared with the controls. Flap tissue blood perfusion was significantly increased postoperatively in Group II. Histological staining indicated that ESW treatment substantially increased vascular endothelial growth factor and proliferating cell nuclear antigen expressions, reduced leukocyte infiltration, and suppression of tumor necrosis factor alpha expression in flap tissue ischemic zones in Group II compared with that in controls. Optimal dosage of ESW treatment has a positive effect in rescuing ischemic zone of flap by increasing tissue perfusion and is associated with suppressing inflammatory response.


In vitro synthesis and assembly of a 68 kDa outer mitochondrial membrane protein from rat liver.
Outer mitochondrial membrane was purified from rat liver. Its constituent proteins were analyzed by SDS-polyacrylamide gel electrophoresis and by electrophoretic immunoblotting employing antibodies raised against total outer mitochondrial membrane. Anti-outer mitochondrial membrane antiserum reacted with only one polypeptide (15 kDa) in rough microsomes, whereas no immunological cross-reactivity was observed with other mitochondrial compartments (intermembrane space, inner membrane, or matrix) or with lysosomes or total cytosol. The antiserum was employed to characterize precursors of outer mitochondrial membrane proteins synthesized in vitro in a rabbit reticulocyte cell-free system. One product (a 68 kDa polypeptide designated OMM-68) bound efficiently to mitochondria in vitro but did not interact with either dog pancreas or rat liver microsomes, either co-translationally or post-translationally. OMM-68 was synthesized exclusively by the membrane-free class of polyribosomes. Attachment of precursor OMM-68 to mitochondria was not accompanied by processing of the polypeptide to a different size.


Malignant pheochromocytoma arising in the organ of Zuckerkandl--a clinicopathological study.
An autopsy case of malignant pheochromocytoma arising in the organ of Zuckerkandl is reported, of which distant metastases were found in the liver and lymph nodes. The biochemical and electron microscopic findings from the tumor tissue showed noradrenaline-secreting type. It was revealed that sex ratio in malignant pheochromocytoma was more prominent in the female, and the frequency of extra-adrenal origin was higher in malignant pheochromocytoma than in benign one from comparative study of reported cases of malignant pheochromocytoma.


Iron intake in relation to ovarian reserve among women seeking infertility treatment.
Is there an association between iron intake and ovarian reserve among women seeking fertility care? Supplemental iron intake above 45 mg/day is associated with lower ovarian reserve among women seeking fertility care. Although the literature regarding iron intake in relation to ovarian reserve is scant and inconsistent, some evidence suggests that iron may have gonadotoxic effects. This observational study included 582 female participants attending the Massachusetts General Hospital Fertility Center (2007-2019) enrolled in the Environment and Reproductive Health (EARTH) Study. Iron intake was estimated using a validated food frequency questionnaire. Markers of ovarian reserve included antral follicle count (AFC) (assessed via transvaginal ultrasound) and Day 3 FSH, both obtained during the course of an infertility evaluation. Participants had a median age of 35 years and median total iron intake of 29 mg/day. Total iron intake was inversely related to AFC and this association was driven by intake of supplemental iron. Compared to women with a supplemental iron intake of ≤20 mg/day, women consuming 45-64 mg/day of supplemental iron had a 17% (-35%, 0.3%) lower AFC and women consuming ≥65 mg/day of supplemental iron had a 32% (-54%, -11%) lower AFC after adjusting for potential confounders (P, linear trend = 0.003). Similarly, in a multivariable-adjusted analysis, Day 3 FSH levels were 0.9 (0.5, 1.3) IU/ml higher among women with a supplemental iron intake of ≥65 mg/day when compared to women with a supplemental iron intake of ≤20 mg/day (P, linear trend = 0.02). Iron intake was estimated using a method that relies on self-report and we had no biomarkers of iron status in our participants; only 36 women consumed ≥45 mg/day of supplemental iron. Since all study participants were seeking fertility treatment, our findings may not apply to women in the general population. Although our findings are consistent with studies of women with iron overload, given the paucity of literature on this topic, it is essential that this question is revisited in studies designed to better understand the dose-response relation of this association across the entire distribution of ovarian reserve and the risk-benefit balance of pre-conceptional iron supplementation given its many positive effects on pregnancy outcomes. The project was funded by Grants R01ES022955, R01ES033651, R01ES009718, P30ES000002, and P30DK046200 from the National Institutes of Health. N.J.-C. was supported by a Fulbright Scholarship. N.J.-C., M.M., L.M.-A., E.O.-P., S.W., I.S., and J.E.C. declare no conflict of interest related to the work in the manuscript. R.H. has received grants from the National Institute of Environmental Health Sciences. N/A.


Delineation of the core aggregation sequences of TDP-43 C-terminal fragment.
Ubiquitinated cytoplasmic inclusions of TDP-43 and its C-terminal cleavage products are the pathological hallmarks of amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitinated inclusions. The C-terminal fragments (CTFs) of TDP-43 are increasingly considered to play an important role in its aggregation and in disease. Here, we employed a set of synthetic peptides spanning the length of the TDP-43 CTF (220-414) in order to find out its core aggregation domains. Two regions, one in the RRM-2 domain (246-255) and the other in the C-terminal domain (311-320) of TDP-43, stand out as highly aggregation prone. Studies done on recombinant purified TDP-43 CTF and its three mutants, in which these sequences were deleted individually and together, suggested that the 311-320 region has a more crucial role to play than the 246-255 in its aggregation. The study helps in defining specific peptide sequences that might form the core of TDP-43 aggregation. Identification of these sequences could help in designing peptide based inhibitors of TDP-43 aggregation.


The role of the dentist and the orthodontist in early diagnosis of Gorlin-Goltz syndrome: a cephalometric and photometric study.
The aim of this study was to analyse the facial characteristics and the craniofacial morphology in GGS patients in order to enable an early diagnosis. Gorlin-Goltz syndrome (GGS) is a autosomic dominant disease, characterised by basal cell carcinoma, palmar/plantar pits, maxillary and mandibular keratocysts and dental abnormalities. Nine out of a sample of 24 GGS patients had complete cephalometric and photographic records at an average age of 8.7 years. Cephalometric and photometric analysis were carried out with standard analyses and compared with healthy patients matched for sex and age. Early diagnosis of GGS based on clinical features could be useful to identify the presence of keratocysts through x-ray examination proceeding with surgical removal at an early stage, limiting space occupying damages.


Chronobiology: The Circadian Clock under Extreme Photoperiods.
Circadian clocks are time-measuring devices found in a majority of organisms synchronizing their behavior and metabolism with the day-light cycle. What happens in extreme latitudes, where the environmental conditions can be harsh at any time of day?


Screening the familial accumulation of kidney malposition and malrotation.
Sacral dystopic kidneys have been found in a couple of brothers and sisters. By screening all the first-grade relatives in one generation, 5 brothers and sisters showed kidney malposition and malrotation. This is the first report in the literature about family screening for this developmental anomaly. Based on the results an autosomal recessive character of the clinical pattern was suggested; it is pointed out that the final clearing of the hereditary process requires further family screenings.


Assessment of the invasion process of the common raccoon Procyon lotor (Carnivora: Procyonidae) on a Mediterranean island a decade after its introduction.
The common raccoon, Procyon lotor was introduced at the Balearic Islands (Spain) in 2006. Since then, a colonization process has been carried out, with captures of specimens in 24.30% of the surface of the whole Mallorca Island. For the first time, information has been provided on the invasive process of P. lotor in an insular ecosystem. 257 specimens of P. lotor were captured during the period 2007-2018, of them 104 were analysed to estimate population parameters. Demographic data showed that the population had a sex ratio of 1.00:1.21 (males:females), high BMI values and up to 40% of females were lactating when captured. Related to diet data, the composition was mainly the same as previous studies around its natural and introduced distribution area. Plant residues represented the 53.25 ± 38.66% followed by invertebrates with 12.22 ± 22.54%, inorganic remains with 11.9 ± 22.07% and finally the vertebrates with 4.94 ± 18.27%. Thus, it is shown how an opportunistic omnivorous species has adapted to the resources provided by the island. Cultivated plants' remains and plastic content in diet evidence that P. lotor is entering in contact with human settlements and agricultural areas. As occurred in other islands where P. lotor was introduced, it is expected that it could become a future problem for the conservation biodiversity in insular ecosystems, as well as for agriculture and human activity. Due to the potential impact on native biodiversity it is necessary to reinforce the implementation of control actions and prevent its expansion to the rest of the island.


Loop analysis of the anal sphincter complex in fecal incontinent patients using functional luminal imaging probe.
Cardiac loops have been used extensively to study myocardial function. With changes in cardiac pump function, loops are shifted to the right or left. Functional luminal imaging probe (FLIP) recordings allow for loop analysis of the anal sphincter and puborectalis muscle (PRM) function. The goal was to characterize anal sphincter area-pressure/tension loop changes in fecal incontinence (FI) patients. Fourteen healthy subjects and 14 patients with FI were studied. A custom-designed FLIP was placed in the vagina and then in the anal canal, and deflated in 20-ml steps, from 90 to 30 ml. At each volume, subjects performed maximal voluntary squeezes. Area-pressure (AP) and area-tension (AT) loops were generated for each squeeze cycle. Three-dimensional ultrasound imaging of the anal sphincter and PRM were obtained to determine the relationship between anal sphincter muscle damage and loop movements. With the increase in bag volume, AP loops and AT loops shifted to the right and upward in normal subjects (both anal and vaginal). The shift to the right was greater, and the upward movement was less in FI patients. The difference in the location of AP loops and AT loops was statistically significant at volumes of 50 ml to 90 ml (P < 0.05). A similar pattern was found in the vaginal loops. There is a significant relationship between the damage to the anal sphincter and PRM, and loop location of FI patients. We propose AP and AT loops as novel ways to assess the anal sphincter and PRM function. Such loops can be generated by real-time measurement of pressure and area within the anal canal.NEW & NOTEWORTHY We describe the use of area-pressure (AP) and area-tension (AT)-loop analysis of the anal sphincters and puborectalis muscles in normal subjects and fecal incontinent patients using the functional luminal imaging probe (FLIP). There are differences in the magnitude of the displacement of the loops with increase in the FLIP bag volume between normal subjects and patients with fecal incontinence. The latter group shifts more to the right in AP and AT space.


Accurate modelling of the retention behaviour of peptides in gradient-elution hydrophilic interaction liquid chromatography.
The applicability of models to describe peptide retention in hydrophilic interaction liquid chromatography (HILIC) was investigated. A tryptic digest of bovine-serum-albumin (BSA) was used as a test sample. Several different models were considered, including adsorption, mixed-mode, exponential, quadratic and Neue-Kuss models. Gradient separations were performed on three different HILIC stationary-phases under three different mobile-phase conditions to obtain model parameters. Methods to track peaks for specific peptides across different chromatograms are shown to be essential. The optimal mobile-phase additive for the separation of BSA digest on each of the three columns was selected by considering the retention window, peak width and peak intensity with mass-spectrometric detection. The performance of the models was investigated using the Akaike information criterion (AIC) to measure the goodness-of-fit and evaluated using prediction errors. The F-test for regression was applied to support model selection. RPLC separations of the same sample were used to test the models. The adsorption model showed the best performance for all the HILIC columns investigated and the lowest prediction errors for two of the three columns. In most cases prediction errors were within 1%.


Carbon dots with strong excitation-dependent fluorescence changes towards pH. Application as nanosensors for a broad range of pH.
In this study, preparation of novel pH-sensitive N-doped carbon dots (NCDs) using glucose and urea is reported. The prepared NCDs present strong excitation-dependent fluorescence changes towards the pH that is a new behavior from these nanomaterials. By taking advantage of this unique behavior, two separated ratiometric pH sensors using emission spectra of the NCDs for both acidic (pH 2.0 to 8.0) and basic (pH 7.0 to 14.0) ranges of pH are constructed. Additionally, by considering the entire Excitation-Emission Matrix (EEM) of NCDs as analytical signal and using a suitable multivariate calibration method, a broad range of pH from 2.0 to 14.0 was well calibrated. The multivariate calibration method was independent from the concentration of NCDs and resulted in a very low average prediction error of 0.067 pH units. No changes in the predicted pH under UV irradiation (for 3 h) and at high ionic strength (up to 2 M NaCl) indicated the high stability of this pH nanosensor. The practicality of this pH nanosensor for pH determination in real water samples was validated with good accuracy and repeatability.


Stepwise adsorption in a mesoporous metal-organic framework: experimental and computational analysis.
Stepwise adsorption in a metal-organic framework with both micro- and meso-pores is caused by adsorbates first filling the micropores, then adsorbing along the mesopore walls, and finally filling the mesopores.


Uptake of blood coagulation factor VIII by dendritic cells is mediated via its C1 domain.
The uptake and processing of blood coagulation factor VIII (FVIII) by antigen-presenting cells and the subsequent presentation of FVIII-derived peptides to CD4(+) T cells direct the immune response to FVIII in patients with hemophilia A. Multiple receptors including mannose receptor and low-density lipoprotein receptor-related protein-1 (LRP1) have been implicated in FVIII uptake. This work studies the involvement of receptor candidates in FVIII uptake by dendritic cells (DCs). Furthermore, we explore FVIII residues that mediate endocytosis. FVIII uptake was performed with human monocyte-derived and murine bone marrow-derived DCs. To investigate FVIII endocytosis, competition assays with soluble receptor ligands, binding studies with recombinant receptor fragments, and small-interfering RNA-induced gene silencing were performed. In addition, FVIII-targeting monoclonal antibodies KM33 and VK34 were used. To confirm in vitro results, hemophilic E17 knockout mice were pretreated with antibodies prior to FVIII injections and anti-FVIII titers were determined. Upon treatment of DCs with mannan or LRP ligand α2-macroglobulin, we observed only a minor decrease in FVIII internalization. In addition, small interfering RNA-mediated knockdown of LRP, mannose receptor, or DC-SIGN expression in monocyte-derived dendritic cells did not prevent FVIII uptake. Binding studies using Fc chimeras revealed that LRP, DC-SIGN, and mannose receptor can bind to FVIII; however, we did not observe a critical role for these receptors in FVIII uptake. Previous studies have shown that human antibodies targeting the C1 (KM33) and A2 (VK34) domains of FVIII interfere with binding to endocytic receptors. Preincubation of FVIII with VK34 did not influence FVIII uptake; however, KM33 completely inhibited FVIII endocytosis by both monocyte-derived dendritic cells and bone marrow-derived dendritic cells. Accordingly, anti-FVIII antibody titers were greatly reduced following the preadministration of KM33 in vivo. Together, our observations emphasize the physiological significance of KM33-targeted residues within the C1 domain in the uptake of FVIII by DCs in vitro and in vivo.


Sequence from early region of polyoma virus DNA containing viral replication origin and encoding small, middle and (part of) large T antigens.
The sequence of about one third of the polyoma virus genome is presented. This sequence covers the origin of replication of two large plaque strains (A2 and A3) of polyoma virus. The two strains differ by 11 bp in the origin region. A model for replication is suggested. The sequence probably also covers the entire coding region of two of the polyoma virus early proteins--small and middle T antigens--as well as part of the coding region for large T antigen. Over a small region of the DNA, all three coding frames contain termination codons, which argues a need for spliced early messenger RNAs. In another region of the DNA, two coding frames can be used. Correlation with protein data suggests that one frame codes for part of middle T antigen and the other for part of large T antigen.


Potential roles of microglial cell progranulin in HIV-associated CNS pathologies and neurocognitive impairment.
Progranulin (PGRN) is a highly unusual molecule with both neuronal and microglial expression with two seemingly unrelated functions, i.e., as a neuronal growth factor and a modulator of neuroinflammation. Haploinsufficiency due to loss of function mutations lead to a fatal presenile dementing illness (frontotemporal lobar degeneration), indicating that adequate expression of PGRN is essential for successful aging. PGRN might be a particularly relevant factor in the pathogenesis of HIVencephalitis (HIVE) and HIV-associated neurocognitive disorders (HAND). We present emerging data and a review of the literature which show that cells of myeloid lineage such as macrophages and microglia are the primary sources of PGRN and that PGRN expression contributes to pathogenesis of CNS diseases. We also present evidence that PGRN is a macrophage antiviral cytokine. For example, PGRN mRNA and protein expression are significantly upregulated in brain specimens with HIVE, and in HIV infected microglia in vitro. Paradoxically, our preliminary CHARTER data analyses indicate that lower PGRN levels in CSF trended towards an association with HAND, particularly in those without detectable virus. Based upon these findings, we introduce the hypothesis that PGRN plays dual roles in modulating antiviral immunity and neuronal dysfunction in the context of HIV infection. In the presence of active viral replication, PGRN expression is increased functioning as an anti-viral factor as well as a neuroprotectant. In the absence of active HIV replication, ongoing inflammation or other stressors suppress PGRN production from macrophages/microglia contributing to neurocognitive dysfunction. We propose.


The Problem of Same-Rater Bias.
The diagnostic process in child and adolescent psychiatry relies heavily on information from multiple informants, including parents, teachers, and the child itself. It has long been well known that information from informants who see the child in different settings may differ, but that each type of informant may contribute useful and unique information to the prediction of mental health problems.1 The diagnosis of attention-deficit/hyperactivity disorder (ADHD) depends on reports from informants who see the child in different settings. This is illustrated in the DSM-5, in which the diagnostic criteria require several inattentive or hyperactive-impulsive symptoms to be present in two or more settings.


Myosin heavy chain isoform immunolabelling in diabetic rats with peripheral neuropathy.
This study evaluated mature and immature myosin heavy chain (MHC) isoform immunolocalisation in soleus muscle of diabetic rats with documented motor neuropathy. Sprague Dawley rats were assigned to one of three groups: control (C), diabetic with insulin (DI), or diabetic without insulin (DNI). Twelve weeks after diabetes induction, soleus muscles were excised and quick-frozen. Cross-sections were labelled immunohistochemically for slow, fast, developmental and neonatal MHC isoforms to determine fiber-type composition. Fiber cross-sectional areas were determined morphometrically. Results revealed that DNI and DI muscles contained greater percentages of myofibers positive for fast MHC compared with controls. DNI animals also showed a lower percentage of myofibers positive for slow MHC compared to the DI group. The number of fibers immunolabelled for developmental MHC isoforms was greater in DNI animals than in the other groups. The differences in slow and fast MHC-labelling appear to indicate a condition of altered neuromuscular activity affecting the diabetic muscles. The increase in developmental MHC-labelling in the DNI muscles could indicate myofiber regeneration or reinnervation that would be more pronounced in the DNI animals in context of their more severe neuropathy. Insulin appeared to influence muscle fiber cross-sectional area and possibly fiber-type grouping frequency; the potential mechanism for these effects was not elucidated.


Uniportal video-assisted thoracoscopic surgery for retained shrapnel in the thoracic cavity: An update surgical approach for removal of foreign body.
Uniportal video-assisted thoracoscopic surgery commonly used for removal of bullet, tumours and foreign bodies in the chest cavity. However, shrapnel fragments related war can injure many organs and life-threatening condition. Furthermore, standard treatment for removal foreign bodies retained in the chest is conventional thoracotomy. Alternatively, single port video-assisted thoracoscopic surgery approach can be used in patients hemodynamically stable. In addition, retained foreign bodies after a penetrating thoracic injury remain challenge for u-VATS surgeons. Here we present A 35-year-old man presented to the emergency department with multiple shells injury associate with right site chest injury. The patient underwent surgery using uniportal video-assisted thoracoscopic surgery u-VATS without spreading of the ribs for removal of a shrapnel retained in the thoracic cavity. The postoperative course was uneventful. On the 2nd day postoperative, the patient was discharged home. The u-VATS approach could be performed by experienced u-VATS surgeons and specialized nurses for this approach. In conclusion, our study revealed that u-VATS is safe, simple and feasible for retained foreign bodies in the thoracic cavity. The u-VATS have many benefits such as decrease postoperative complication, pain and earlier return to work.


Light-induced metal-like surface of silicon photonic waveguides.
The surface of a material may exhibit physical phenomena that do not occur in the bulk of the material itself. For this reason, the behaviour of nanoscale devices is expected to be conditioned, or even dominated, by the nature of their surface. Here, we show that in silicon photonic nanowaveguides, massive surface carrier generation is induced by light travelling in the waveguide, because of natural surface-state absorption at the core/cladding interface. At the typical light intensity used in linear applications, this effect makes the surface of the waveguide behave as a metal-like frame. A twofold impact is observed on the waveguide performance: the surface electric conductivity dominates over that of bulk silicon and an additional optical absorption mechanism arises, that we named surface free-carrier absorption. These results, applying to generic semiconductor photonic technologies, unveil the real picture of optical nanowaveguides that needs to be considered in the design of any integrated optoelectronic device.


Modulation of pentylenetetrazol-induced seizure activity by branched-chain amino acids and alpha-ketoisocaproate.
Branched-chain amino acids, and mainly leucine act as nitrogen donors in the cerebral glutamate-glutamine cycle, thereby reducing brain excitability. Rats equipped with cortical electrodes received 300 mg/kg of leucine, isoleucine, valine or the ketoacid of leucine, alpha-ketoisocaproate at 2 h before the induction of seizures by 40 mg/kg pentylenetetrazol. Control groups received saline or a commercial mixture of amino acids, Vamine(R). Leucine and isoleucine increased the latency to absence-like and tonic-clonic seizures but did not influence the duration of the tonic-clonic seizure. Vamine(R), valine and alpha-ketoisocaproate had no effect. These data are consistent with the role of leucine in buffering brain glutamate concentration.


Studies of ammonia loading: effects of rate of delivery and enhanced removal of NH4 on blood levels of ammonia and coma induction.
Using dose-response curves, the dose of NH4Ac inducing coma in one-half of the animals was increased by 60 to 80% after 1 mmol of arginine. The larger increase occurred in larger rats but was not proportional to the increase in weight. Incremental subcoma doses of NH4 raised the amount of NH4 required for inducing coma and the brain level of ammonia at the point of coma. After a portacaval shunt the results were similar, although lower doses of NH4 were required from the beginning. Blood ammonias after a loading dose (1.25 mmol) of NH4 were influenced by the duration of a preinfusion of NH4 and by the preinjection of various amino acids involved in the disposal of NH4 in the urea cycle. The amount of reduction in blood ammonia by ornithine and arginine compounds was less the longer the preinfusion of NH4. Blood ammonia was not lowered by glutamate at any time but was increased with longer preinfusion periods. Hepatectomy (Hx) reduced the removal of an NH4 load. After a modest load (0.85 mmol) of NH4, blood ammonia increased 5-fold, over that of sham-operated rats, with 70% Hx and 15-fold with 90% Hx. Ornithine reduced these blood ammonias by about 50%. Arginine had no effect. These studies indicate ways of reducing toxicity of NH4 and factors that predispose to or enhance toxicity.


Urinary control after the definitive reconstruction of cloacal anomaly.
Urinary control after definitive repair of a cloacal anomaly is difficult to achieve. The present report aims to describe the clinical course of urinary control, and the need for the management of bladder dysfunction after reconstruction. The present consecutive series consisted of 11 girls who underwent definitive repair of cloacal anomalies over a period of 11 years. Eight patients were associated with hydrocolpos. Radiological examination included a plain X-ray radiograph of the lumbosacral spine and a voiding cystourethrography with or without a urodynamic study. Reconstruction of the cloaca was performed on patients aged between 1 and 3 years using a posterior sagittal approach. Vaginal reconstruction was carried out 13 times in 11 patients using tubularized vaginal flap, distal rectal segment, perineal skin flap, or total urogenital sinus mobilization. Cystostomy or vesicostomy was carried out in four newborns/infants. Another seven patients could void spontaneously but incompletely with residual urine. Occult spinal dysraphism was found in five patients and hemisacrum in two patients. After definitive reconstruction, most patients acquired an adequate to normal bladder volume for 1-year-olds. Normal detrusor-sphincter function was seen in three patients. Detrusor areflexia was seen in two patients who underwent in utero vesico-amniotic shunt. Detrusor underactivity was observed in six patients. Bladder compliance was good in all patients except for one. No patients in the present series showed persistent urinary incontinence from the bladder neck or urethral dysfunction. It is postulated that wetting after definitive repair may be the result of overflow incontinence and poor bladder contractility rather than sphincter injury. The main clinical characteristic of bladder dysfunction was a failure to empty. We could not define the exact etiology, but iatrogenic injury from extensive dissection can lead to the higher risks of peripheral nerve damage. Accomplishment of definitive repair involves not only anatomical reconstruction, but also postoperative urinary control, including the initiation of clean intermittent catheterizations under repeated urodynamic evaluations.


[Management of acute bronchiolitis in newborns].
Acute bronchiolitis is a common condition of viral origin with attention of treating hypoxia and maintaining hydration. Medications are often ineffective, although widely used in our countries. If the spontaneous cure is the rule, the persistence of a respiratory symptomatology (cough or wheezing) during several weeks is not exceptional.


A thiolate-bridged FeIVFeIV μ-nitrido complex and its hydrogenation reactivity toward ammonia formation.
Iron nitrides are key intermediates in biological nitrogen fixation and the industrial Haber-Bosch process, used to form ammonia from dinitrogen. However, the proposed successive conversion of nitride to ammonia remains elusive. In this regard, the search for well-described multi-iron nitrido model complexes and investigations on controlling their reactivity towards ammonia formation have long been of great challenge and importance. Here we report a well-defined thiolate-bridged FeIVFeIV μ-nitrido complex featuring an uncommon bent Fe-N-Fe moiety. Remarkably, this complex shows excellent reactivity toward hydrogenation with H2 at ambient conditions, forming ammonia in high yield. Combined experimental and computational studies demonstrate that a thiolate-bridged FeIIIFeIII μ-amido complex is a key intermediate, which is generated through an unusual two-electron oxidation of H2. Moreover, ammonia production was also realized by treating this diiron μ-nitride with electrons and water as a proton source.