Remediation of industrial wastewater using four hydrophyte species: A comparison of individual (pot experiments) and mix plants (constructed wetland).
Remediation and management of industrial wastewater (IWW) using hydrophytes act as one of the cost effective and environmentally friendly technologies. The present study was conducted to assess the role and efficiency of selected four hydrophyte species through constructed wetland (CW) for the removal of heavy metals (HMs) from IWW. Samples of wastewater (WW) were collected from the main drain of Hayatabad Industrial Estate (Peshawar, Pakistan) and analysed for HMs like cadmium (Cd), copper (Cu) and lead (Pb) along with basic physicochemical parameters like pH, electric conductivity (EC), total suspended solids (TSS), total dissolved solids (TDS), dissolved oxygen (DO), biological oxygen demand (BOD), chemical oxygen demand (COD), dissolved organic carbon (DOC) through standard analytical methods. Four hydrophytes species such as Typha latifolia (cattail), Eichhornia crassipes (water hyacinth), Lemna gibba (duck weed) and Pistia stratiotes (water cabbage) were transplanted into CW (mix cultivation). Each selected species was also cultivated in individual pots for investigating their efficiency to remove HMs. The Cd, Cu and Pb removal efficiency of CW was recorded as 39.5%, 80.3% and 85.5%, respectively. The removal efficacy of hydrophyte species including cattail, water hyacinth, duck weed and water cabbage was 96.2%, 72.2%, 60.4% and 93.3%, respectively for Cd, while 83.6%, 82.3%, 90.0% and 81.7% for Cu and 95.9%, 78.0%, 91.3% and 97.1% for Pb, respectively. Findings of T-Test and One-Way ANOVA showed that the concentrations of Cd, Cu and Pb in IWW were significantly (P ≤ 0.01) reduced by the treatment of hydrophytes revealing the higher efficiency of CW and selected species used in this study. The HMs were removed in order of Pb > Cu > Cd. Most efficient removal for Cd was found by water cabbage, Cu by duck weed and Pb by water hyacinth. It was concluded that CW is one of the environmentally friendly and cost-effective technologies that can be used for the treatment of IWW due to the efficiency of hydrophytes species in terms of HMs removal.


Replication bypass model of sister chromatid exchanges and implications for Bloom's syndrome and Fanconi's anemia.
A model of the sister chromatid exchange (SCE) process is outlined as a replication mechanism to bypass DNA crosslinks. The model suggests that when normal bidirectional replication advances from both sides towards a crosslink along the two opposite parental strands, the complementary parental strand segments can be temporarily displaced at each contralateral 5' side from the crosslink. The free ends produced in this first step will be terminally aligned but will have opposite polarity. The second step of the bypass can, however, be completed by either of two rejoining processes--terminal ligation of the free ends via nascent Okazaki pieces or aberrant complementation by overlapping the free ends. This bypass mechanism (1) allows replication to continue past a crosslink leaving it intact but (2) results in the switching of parental strands and their attached incomplete nascent strands above and below the crosslink site producing an exchange between sister chromatids. This model is compatible with the findings of current SCE studies using the new BUDR/stain techniques as well as with previous autoradiographic studies. It also suggests that the chromatid breaks and deletions in Fanconi's Anemia represent a defect in step two of the replication bypass mechanism and that the high frequency of SCE's and quadriradials in Bloom's Syndrome represent the SCE overload effects of a defect in crosslink repair.


Influence of nucleotides on the secondary structure and on the thermal stability of mitochondrial F1 visualized by infrared spectroscopy.
We have studied the secondary structure of mitochondrial F1 using infrared spectroscopy. Our results show that in the absence of added nucleotides this complex contains similar percentages of alpha-helices, beta-structures and reverse turns (30%, 28% and 31%, respectively). The influence of ADP and ATP on the different types of secondary structure was determined; when all the nucleotide-binding sites were occupied, small but reproducible changes were observed, corresponding to a decrease in beta-structure and an increase in alpha-helix and reverse turns. The effect of nucleotide binding on the thermal stability of F1 was also studied; the thermal denaturation temperature, 55 degrees C, was increased by 11 degrees C and 7 degrees C by ATP and ADP, respectively. These results indicate that nucleotide binding affects the secondary structure of F1, stabilizing the complex.


Gene frequencies in the cat deme of Tampa, Florida.
The frequencies of mutant alleles at five loci were calculated for a sample of cats from the deme of Tampa, Florida. Owing to certain diagnostic problems, precise comparisons to other populations are unwarranted. However, there is general concordance with other U.S. cat populations.


Bilateral primary extramedullary orbital plasmacytomas.
An 81-year-old man presented with bilateral orbital tumors that were found to be extramedullary plasmacytomas. Immunoperoxidase staining of the tissue was positive for IgG-kappa; no lambda chains were seen. Results of serum immunoelectrophoresis were positive for monoclonal IgG-kappa. Test results of the urine were positive for Bence Jones protein; only kappa chains were seen on radial diffusion. Systemic evaluation failed to show tumor elsewhere. The patient was treated with radiation and low-dose melphalan/prednisone, with good response. Five years later, the results of immunoelectrophoresis are normal and there is no clinical evidence of tumor; however, a small amount of kappa light chains remains in the urine. This case supports the important therapeutic and prognostic differences among orbital involvement in extramedullary plasmacytoma, solitary myeloma of bone, and multiple myeloma.


Noninvasive and simultaneous quantitative analysis of multiple human blood components based on the grey analysis system.
Noninvasive detection of human blood components is the dream of human beings and the goal of clinical detection. From the perspective of mathematical analysis, based on the grey analysis system, the principle of spectral chemical quantitative analysis and the solution method of multivariate linear equation, this paper pioneers the spectrum elimination method, and obtains a complete, high-precision, synchronous and noninvasive detection system for a variety of human blood components. The spectral elimination method applies the principle of elimination method in mathematics to the noninvasive quantitative analysis of human blood components by spectral method, reduces the influence of non-target components on the detection of target components, and improves the accuracy of noninvasive quantitative analysis of human blood components. To demonstrate the effectiveness of the method, taking the analysis of the contents of seven blood components (hemoglobin, red blood cell count, neutrophils, lymphocytes, monocytes, eosinophils and basophils) in blood as an example, fourteen models were established by two different methods. From the comparison of modeling results, it can be concluded that when the seven models established by spectral elimination method predict the corresponding seven components of all samples, the predicted correlation coefficients are more than 0.9500. The experimental results show that the spectral elimination method and non-invasive detection system proposed can predict the content of human blood components with high accuracy. This paper studies a high-precision, simultaneous and noninvasive quantitative analysis system of multiple human blood components for the first time, which not only makes great progress in the non-invasive chemical quantitative analysis of human blood components by spectroscopy, but also has great application value for clinical medical treatment and disease diagnosis.


Mirror quality and efficiency improvements of reflective spatial light modulators by the use of dielectric coatings and chemical-mechanical polishing.
To date, silicon backplane spatial light modulators have been characterized by poor-quality mirrors. Hillock formation during metal sintering has been identified as the source of this problem. Here hillock elimination is achieved by constraining the metal with a low-temperature plasma-enhanced chemicalvapor deposition silicon dioxide coating. A double-layer metallization procedure increases the silicon area available for circuitry and improves the mirror fill factor. Second-layer metal mirrors require a flat, intermediate dielectric substrate. Chemical-mechanical polishing is demonstrated to provide the flatness necessary to achieve high optical quality.


Hybrid Density Functional Methods Empirically Optimized for the Computation of (13)C and (1)H Chemical Shifts in Chloroform Solution.
Two hybrid generalized-gradient approximation density functionals, WC04 and WP04, are optimized for the prediction of (13)C and (1)H chemical shifts, respectively, using a training set of 43 molecules in chloroform solution. Tests on molecules not included in the training set, namely six stereoisomeric methylcyclohexanols and a β-lactam antibiotic, indicate the models to be robust and moreover to provide results more accurate than those from equivalent B3LYP, PBE1, or mPW1PW91 calculations, particularly for the prediction of downfield resonances in nuclear magnetic resonance spectra. However, linear regression of the B3LYP, PBE1, and mPW1PW91 predicted values on the experimental data improves the accuracy of those models so that they are comparable to WC04 and WP04.


Autophagy inhibits the mesenchymal stem cell aging induced by D-galactose through ROS/JNK/p38 signalling.
Autophagy and cellular senescence are two critical responses of mammalian cells to stress and may have a direct relationship given that they respond to the same set of stimuli, including oxidative stress, DNA damage, and telomere shortening. Mesenchymal stem cells (MSCs) have emerged as reliable cell sources for stem cell transplantation and are currently being tested in numerous clinical trials. However, the effects of autophagy on MSC senescence and corresponding mechanisms have not been fully evaluated. Several studies demonstrated that autophagy level increases in aging MSCs and the downregulation of autophagy can delay MSC senescence, which is inconsistent with most studies that showed autophagy could play a protective role in stem cell senescence. To further study the relationship between autophagy and MSC senescence and explore the effects and mechanisms of premodulated autophagy on MSC senescence, we induced the up- or down-regulation of autophagy by using rapamycin (Rapa) or 3-methyladenine, respectively, before MSC senescence induced by D-galactose (D-gal). Results showed that pretreatment with Rapa for 24 hours remarkably alleviated MSC aging induced by D-gal and inhibited ROS generation. p-Jun N-terminal kinases (JNK) and p-38 expression were also clearly decreased in the Rapa group. Moreover, the protective effect of Rapa on MSC senescence can be abolished by enhancing the level of ROS, and p38 inhibitor can reverse the promoting effect of H2 O2 on MSC senescence. In summary, the present study indicates that autophagy plays a protective role in MSC senescence induced by D-gal, and ROS/JNK/p38 signalling plays an important mediating role in autophagy-delaying MSC senescence.


Surgical management of the pancreatic pseudocyst in children: a long-term evaluation.
Pseudocyst of the pancreas is an uncommon disorder in children. During the period of 1977 to 1990, the authors reviewed the records of 10 consecutive patients with pancreatic pseudocyst (PP) who were surgically treated in our institution. In 8 patients, the surgical procedure that was used was transgastric cystogastrostomy, and in 1 patient it was total excision of the pseudocyst. The remaining 1 patient underwent external drainage. After an average follow-up of previous operation except the 1 patient who was treated with external drainage. Biochemical tests, abdominal ultrasonographies, and barium meals were also normal in 9 patients. The analysis of the results indicates that despite new percutaneous therapeutic modalities, it is still an internal drainage through transgastric cystogastrostomy that should be favored in treatment of PP in children.


Noninvasive evaluation of mitral regurgitation by analysis of left atrial signal loss in cine magnetic resonance.
Magnetic resonance imaging that uses shallow flip angles, short repetition times, and gradient refocused echoes results in multiple images throughout the cardiac cycle in which the blood pool has high signal intensity. In cine magnetic resonance images, disturbed (high velocity) blood flow produces a loss of signal intensity within the intracavitary blood pool, which makes this technique potentially useful for evaluating valvular disease. Multilevel cine magnetic resonance imaging was performed in 26 patients with mitral regurgitation (MR) documented and graded for severity by Doppler echocardiography or contrast ventriculography. Intracavitary left atrial signal intensity was analyzed in order to derive parameters that reflect the severity of the lesion. Seven normal volunteers were studied for comparison. All regurgitant lesions were visualized in cine magnetic resonance images as discrete regions of systolic signal loss extending from the mitral valve into the left atrium. The extent and degree of signal loss correlated well with severity. In patients with mild MR, signal loss was seen in 3.3 +/- 1.2 (+/- SD) anatomic levels compared to 4.9 +/- 1.4 levels in patients with moderate MR (p = NS), and in 7.0 +/- 1.4 levels in patients with severe MR (p less than 0.001 versus mild MR). The total area of maximal systolic left atrial signal loss seen in all levels was 10 +/- 6 cm2 in mild versus 31 +/- 17 cm2 in moderate (p less than 0.001) and 96 +/- 30 cm2 in severe MR (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Lead poisoning of raccoons in Connecticut.
A wild raccoon (Procyon lotor) had clinical signs, histopathologic and ultrastructural lesions indicative of lead intoxication. The diagnosis was confirmed by chemical analyses of liver and kidney tissues which revealed 35 ppm of lead in wet tissues. A survey of hepatic lead concentration in 13 additional raccoons was conducted.


Influence of prostaglandin-synthesis inhibitors on carbachol- and histamine-induced vasodilatation in perfused rat hindquarters.
In perfused rat hindquarters, in which vascular tone was maintained by norepinephrine, carbachol-induced dilatations were blocked by atropine (10(-7) M), while histamine dilatations were inhibited as well by mepyramine (10(-6) M) as by cimetidine (10(-5) M) indicating a histamine effect through both H1- and H2-receptors. This double-receptor histamine effect was confirmed by the observation that specific H1- and H2-receptor agonists, respectively PEA (2-pyridyl-ethyl-aminedihydrochloride) and dimaprit also produced a vasodilatation. Carbachol- and histamine-induced dilatations were also inhibited by ETYA (5,8,11,14-eicosatetraynoic acid) and quinacrine but not by indomethacin. The inhibition of the histamine vasodilatation appeared to rest on an interference with the H1-receptor mechanism. It is concluded that metabolites of arachidonic acid possibly mediate the dilating effect of carbachol, acting through muscarine receptors, and of histamine, acting through H1-receptors.


FtsZ dynamics in bacterial division: What, how, and why?
Bacterial cell division is orchestrated by the divisome, a protein complex centered on the tubulin homolog FtsZ. FtsZ polymerizes into a dynamic ring that defines the division site, recruits downstream proteins, and directs peptidoglycan synthesis to drive constriction. Recent studies have documented treadmilling of FtsZ polymer clusters both in cells and in vitro. Emerging evidence suggests that FtsZ dynamics are regulated largely by intrinsic properties of FtsZ itself and by the membrane anchoring protein FtsA. Although FtsZ dynamics are broadly required for Z-ring assembly, their role(s) during constriction may vary among bacterial species. These recent advances set the stage for future studies to investigate how FtsZ dynamics are physically and/or functionally coupled to peptidoglycan metabolic enzymes to direct efficient division.


Gabapentin attenuates late but not early postoperative pain after thyroidectomy with superficial cervical plexus block.
Preoperative oral gabapentin has been shown to reduce postoperative pain. However, the effects of gabapentin as an adjunct to regional anesthesia is unclear and its effects on chronic pain remains unknown. In patients undergoing thyroidectomy, we investigated the effects on early and late (at 6 mo) postoperative pain of preoperative oral gabapentin as an adjunct to superficial cervical plexus block (SCPB). Fifty consecutive consenting patients were randomized to receive either 1200 mg of gabapentin (Group G) or placebo (Group P) 2 h preoperatively. Preoperative anxiety was assessed on a numeric scale from 0 to 6. A SCPB was performed after a standardized induction of anesthesia. The primary outcome, analgesic drug consumption, was assessed during the procedure and postoperatively in the postanesthesia care unit and after discharge to the ward. Over the first 24 h, pain levels at rest and during swallowing were measured on a numeric scale from 0 to 10. If the pain level was more than 4/10 at rest, patients received 1 g/6 h of IV paracetamol and/or 50 mg/6 h of IV tramadol as a rescue analgesic treatment in the interval. The day before operation and 6 mo after thyroidectomy, included patients were asked to answer a neuropathic pain diagnostic questionnaire. Population characteristics, preoperative anxiety, intraoperative drug consumption, procedure duration, and postoperative care unit stay were comparable in both groups. Analgesic consumption during the first 24 postoperative hours was similar in both groups (G: 3 [0-5] doses/24 h; P: 3 [1-5] doses/24 h; P = NS), as well as pain at rest (G: 2,2 [0.2-3.7]; P: 2 [0-6.3]; P = NS), and during swallowing (G: 2.8 [0.4-8.9]; P: 3 [1.4-6.3]; P = NS]). Eight patients had a diagnostic questionnaire score more than 3, 6 mo after operation versus 2 in preoperative period (P = 0.04). Such delayed neuropathic pain complaints were reported in seven patients receiving SCPB alone and only in one patient receiving both SCPB and preoperative adjunctive oral gabapentin. (P = 0.01). Oral preoperative administration of gabapentin did not modify immediate pain management in thyroidectomy patients receiving SCPB, but prevented delayed neuropathic pain at 6 mo.


Effect of roscovitine pretreatment on in vitro maturation of oocytes and their subsequent developmental after chemical activation in dromedary camel (Camelus dromedarius).
Studies were conducted to evaluate an optimal concentration of roscovitine needed to maintain abattoir origin oocytes at germinal vesicle stage in experiment 1 and their subsequent maturation and developmental competence after chemical activation in experiments 2 and 3, respectively. The cumulus-oocyte complexes (COCs) aspirated from ovaries collected from a local slaughterhouse were cultured in TCM-199 based pre-maturation medium supplemented with 25, 50 or 75 μM roscovitine, depending on the experimental group. After 24 h, the COCs were denuded of cumulus, fixed and stained with aceto-orcein and examined for their nuclear status. They were classified as germinal vesicle, diakinesis, metaphase-I, metaphase-II and those with degenerated, fragmented, scattered, activated or without visible chromatin as others. In experiment 2, the COCs pre-matured in media supplemented with 50 μM roscovitine for 24 h were washed and kept for in vitro maturation along with another group of freshly collected COCs for 30 h. All the oocytes were fixed and stained to evaluate their nuclear status as described above. In experiment 3, all mature oocytes obtained from the COCs pre-matured in media supplemented with 50 μM roscovitine and those obtained from freshly collected group were activated by 5 mM ionomycin. Activated oocytes were cultured in embryo culture medium for a period of 7 days to evaluate their developmental potential. The proportion of oocytes at GV stage in the group pre-matured in media with 50 μM-was significantly (P < 0.01) higher when compared with the group having 25 μM of roscovitine. No difference was found in the proportion of GV stage oocytes in this group when compared with the freshly collected COCs. None of the oocytes reached to M-II stage in any of the three treatment groups. In experiment 2, no difference was observed in the proportion of oocytes reaching M-II stage between the groups after 30 h of in vitro culture; however, higher proportion of oocytes (P < 0.05) were classified as others in the pre-maturation group when compared with the group having freshly collected oocytes. In experiment 3, no difference was observed in the proportion of oocytes cleaving and those developing to the blastocyst stage between the pre-matured and freshly matured groups. In conclusion, the present study, for the first time, demonstrates the possible use of roscovitine as a meiotic inhibitor for camel oocytes. Keeping in view the ability of these oocytes to mature and develop to the blastocyst stage at par with the fresh oocytes, more flexible schedules for maturation and manipulation of such oocytes could be developed.


Analysis of the Trend and Seasonal Cycle of Carbon Monoxide Concentrations in an Urban Area (4 pp).
Air quality is an field of major concern in large cities. This problem has led administrations to introduce plans and regulations to reduce pollutant emissions. The analysis of variations in the concentration of pollutants is useful when evaluating the effectiveness of these plans. However, such an analysis cannot be undertaken using standard statistical techniques, due to the fact that concentrations of atmospheric pollutants often exhibit a lack of normality and are autocorrelated. On the other hand, if long-term trends of any pollutant's emissions are to be detected, meteorological effects must be removed from the time series analysed, due to their strong masking effects. The application of statistical methods to analyse temporal variations is illustrated using monthly carbon monoxide (CO) concentrations observed at an urban site. The sampling site is located at a street intersection in central Valencia (Spain) with a high traffic density. Valencia is the third largest city in Spain. It is a typical Mediterranean city in terms of its urban structure and climatology. The sampling site started operation in January 1994 and monitored CO ground level concentrations until February 2002. Its geographic coordinates are W0º22'52\ N39º28'05\ and its altitude is 11 m. Two nonparametric trend tests are applied. One of these is robust against serial correlation with regards to the false rejection rate, when observations have a strong persistence or when the sample size per month is small. A nonparametric analysis of the homogeneity of trends between seasons is also discussed. A multiple linear regression model is used with the transformed data, including the effect of meteorological variables. The method of generalized least squares is applied to estimate the model parameters to take into account the serial dependence of the residuals of this model. This study also assesses temporal changes using the Kolmogorov-Zurbenko (KZ) filter. The KZ filter has been shown to be an effective way to remove the influence of meteorological conditions on O3 and PM to examine underlying trends. The nonparametric tests indicate a decreasing, significant trend in the sampled site. The application of the linear model yields a significant decrease every twelve months of 15.8% for the average monthly CO concentration. The 95% confidence interval for the trend ranges from 13.9% to 17.7%. The seasonal cycle also provides significant results. There are no differences in trends throughout the months. The percentage of CO variance explained by the linear model is 90.3%. The KZ filter separates out long, short-term and seasonal variations in the CO series. The estimated, significant, long-term trend every year results in 10.3% with this method. The 95% confidence interval ranges from 8.8% to 11.9%. This approach explains 89.9% of the CO temporal variations. The differences between the linear model and KZ filter trend estimations are due to the fact that the KZ filter performs the analysis on the smoothed data rather than the original data. In the KZ filter trend estimation, the effect of meteorological conditions has been removed. The CO short-term component is attributable to weather and short-term fluctuations in emissions. There is a significant seasonal cycle. This component is a result of changes in the traffic, the yearly meteorological cycle and the interactions between these two factors. There are peaks during the autumn and winter months, which have more traffic density in the sampled site. There is a minimum during the month of August, reflecting the very low level of vehicle emissions which is a direct consequence of the holiday period. The significant, decreasing trend implies to a certain extent that the urban environment in the area is improving. This trend results from changes in overall emissions, pollutant transport, climate, policy and economics. It is also due to the effect of introducing reformulated gasoline. The additives enable vehicles to burn fuel with a higher air/fuel ratio, thereby lowering the emission of CO. The KZ filter has been the most effective method to separate the CO series components and to obtain an estimate of the long-term trend due to changes in emissions, removing the effect of meteorological conditions. . Air quality managers and policy-makers must understand the link between climate and pollutants to select optimal pollutant reduction strategies and avoid exceeding emission directives. This paper analyses eight years of ambient CO data at a site with a high traffic density, and provides results that are useful for decision-making. The assessment of long-term changes in air pollutants to evaluate reduction strategies has to be done while taking into account meteorological variability.


Elemental analysis of natural quartz from Um Higlig, Red Sea Aea, Egypt by instrumental neutron activation analysis.
A scheme for INAA of 25 elements: As, Ba, Ca, Ce, Co, Cr, Cs, Eu, Fe, Hf, K, La, Lu, Mg, Mn, Na, Nd, Rb, Sc, Sm, Th, U, Yb, Zn and Zr in quartz collected from the eastern desert along the Egyptian Red Sea coast is proposed. The samples were prepared together with standard reference material and irradiated in a neutron flux of 7×10(11)n/cm(2)s in the TRIGA Mainz research reactor facilities. The gamma spectra were collected by a HPGe detector and the analysis was done by a computerized multichannel analyzer.The accuracy of the procedure is evaluated by the analysis of two geo-standard reference materials (Dolerite WSE and Microgabro PMS). The choice of the nuclear reaction, irradiation and decay times and of the proper gamma radiation in counting are presented and discussed. The data presented here are our contribution to understanding the elemental composition of the quartz rock. Because there are no existing databases for the elemental analysis of quartz, our results are a start to establishing a database for the Egyptian quartz. It is hoped that the data presented here will be useful to those dealing with geochemistry, quartz chemistry and related fields.


Skin oncoplasties: O-to-Z technique a technique of choice in situation of limited resources? Case of Burkina Faso.
In developing countries, the long delays in consultation lead to a delay in diagnosis and management of the skin tumors. The lesions are often large and bring the problem of skin coverage after their resections. Several reconstruction techniques allow skin coverage. The objective of this study is to describe the place of O-to-Z technique in the surgical treatment of skin cancers in Ouagadougou. We hypothesized that O-to-Z technique reduces healing times and the number of dressings compared with directed wound healing. It was a two-center, retrospective, descriptive study on O-to-Z technique in skin cancers. It included patients who underwent surgery between January 1st, 2013 and March 30th, 2021 in Ouagadougou. Scar quality and healing time in Z-plasty were compared with those of secondary healing. We used the Student's t test. In 8 years and 3 months, 171 skin cancers were identified. The mean time to consultation was 13.6 months. The average size of the tumors was 9 cm. An O-to-Z technique was performed in 42 cases, being 58.3% of the patients operated on. The average healing time was 15 days. It was four and a half times shorter in O-to-Z technique than in secondary healing. Ischemic necrosis of the Z-corner was noted in 7 cases. The recurrence rate in O-to-Z technique and secondary healing was 7.1% and 9.1% respectively. Hypertrophic or keloidal scars were noticed in 7 cases and hypochromia in 2 cases. O-to-Z technique is a technique of choice for skin coverage after large resections in surgical oncology. It reduces the healing time and the cost of postoperative care without increasing the risk of tumor recurrence.


Possible role of surface potential in the gating mechanism of Ca2+ channels in cat adrenal chromaffin cells: studies with fura-2 microfluorometry.
The cytosolic free Ca2+ concentration ([Ca]in) in isolated cat chromaffin cells was measured by fura-2 microfluorometry. During 30 mM KCl depolarization or sucrose substitution for NaCl, a reduction in external Ca2+ concentration under optimal conditions paradoxically caused a rise in [Ca]in and, in separate experiments, in catecholamine secretion. The results support a previously suggested role of surface potentials in the gating mechanism of Ca2+ channels.


Breast Cancer Knowledge and Screening Practice and Barriers Among Women in Madinah, Saudi Arabia.
A breast screening program may help to reduce cancer mortality rates among women. However, the use of the screening program by women in Madinah city is low, and studies examining its practice and barriers of low uptake are sparse. To identify breast cancer knowledge, practice and screening barriers among women attending primary health centers (PHC) in Madinah, Saudi Arabia. A primary health center-based cross-sectional study was performed in Madinah city in 2015. A multistage stratified cluster sample was obtained and included 465 women (15 years and older) from five PHC. Data concerning socio-demographics, knowledge about breast cancer, and practice and barriers of mammography use were collected using a structured questionnaire. The mean age of the studied 465 women was 34.9 ± 12.2 years. Of these women, 27.7 and 38.5 % received mammography and performed breast self-examination, respectively. A high level of poor knowledge about breast cancer was detected in the overall studied women and those who never received a mammography, particularly knowledge related to the risk factors of breast cancer. The most important predictors of the barriers to mammography were incorrect beliefs about mammography and its procedures. A belief that mammography is painful was significantly associated with a 56 % reduction in its use (OR = 0.44; 95 % CI = 0.22-0.88). The high levels of poor knowledge about cancer breast observed in this study reflect the need for greater efforts to increase breast awareness education.


2-Deoxy-D-glucose attenuates isoflurane-induced cytotoxicity in an in vitro cell culture model of H4 human neuroglioma cells.
β-Amyloid protein (Aβ) accumulation and caspase activation have been shown to contribute to Alzheimer disease neuropathogenesis. Aβ is produced from amyloid precursor protein through proteolytic processing by aspartyl protease β-site amyloid precursor protein-cleaving enzyme (BACE). The inhaled anesthetic isoflurane has been shown to induce caspase activation and increase levels of BACE and Aβ. However, the underlying mechanisms and interventions of the isoflurane-induced neurotoxicity remain largely to be determined. The glucose analog 2-deoxy-d-glucose (2-DG) has neuroprotective effects. Therefore, we sought to determine whether 2-DG can reduce caspase-3 activation and the increase in the levels of BACE and reactive oxygen species (ROS) induced by isoflurane. H4 human neuroglioma cells were treated with saline or 2-DG (5 mM) for 1 hour followed by a control condition or 2% isoflurane for 6 hours. The levels of caspase-3 cleavage (activation), BACE, cytosolic calcium, and ROS were determined. Two-way analysis of variance was used to assess the interactions of 2-DG and isoflurane on caspase-3 activation, and levels of BACE and ROS. In H4 human neuroglioma cells, 2-DG reduced the caspase-3 activation (477% vs 186%, F = 8.68; P = 0.019) and the increase in BACE levels (345% vs 123%, F = 42.24; P = 0.0002) induced by isoflurane. 2-DG decreased the levels of cytosolic calcium and ROS (100% vs 66%, F = 1.94; P = 0.014). These results suggest that 2-DG may decrease oxidative stress and increase cytosolic calcium levels, thus attenuating isoflurane-induced neurotoxicity.


[Technics and indications of limited petrosectomy. Value of the combined transcochlear and infratemporal approach].
The authors describe the extended trans-cochlear approach and define its indications on the basis of a series of 10 cases operated by the transcochlear approach, 6 of which were extended. This approach has a well defined indication between the trans-cochlear approach described by W. House and the infra-temporal approach described by Fish.


Retrospective study of endoscopic submucosal tunnel dissection (ESTD) for surgical resection of esophageal leiomyoma.
Esophageal leiomyoma is benign and often asymptomatic, but if the tumor is too large or obstructive, it should be resected. The aim of this study was to compare a novel approach, endoscopic submucosal tunnel dissection (ESTD), with a more established method, endoscopic submucosal dissection (ESD). This was a retrospective study of 39 patients in Chongqing Xinqiao Hospital, China, undergoing resection for leiomyoma >2 cm in diameter, or 1.5-2.0 cm in diameter with symptoms of obstructive dysphagia. Epidemiological data, presenting symptoms, diagnostic investigations, tumor location, histopathological findings, and safety and efficacy of surgical resection were analyzed. Mean tumor sizes in the ESTD (n = 18; mean age = 36.7 ± 6.3 years) and ESD (n = 21; age = 41.0 ± 4.4 years) groups were 3.3 ± 0.7 and 3.0 ± 0.4 cm, respectively. The male:female ratio was 25:14, with a distribution of lesions among the lower, middle, and upper esophagus of 22:14:3. Operating time was significantly shorter (p < 0.05) for ESTD (67.5 ± 9.5 min) than for ESD (87.2 ± 7.7 min), while incision healing was faster (p < 0.05) for ESTD (14.7 ± 2.5 days) than for ESD (57.9 ± 7.5 days). Hospital stay was also shorter (p < 0.05) for ESTD (2.3 ± 0.5 days) than for ESD (5.7 ± 1.0 days). Bleeding was the only complication with ESTD (3/18 patients), with no significant difference in the incidence of complications between groups. ESTD was rapidly learned by surgeons. ESTD is a safe and effective treatment for esophageal leiomyoma, with advantages over ESD.


An equine herpesvirus 1 mutant with a lacZ insertion between open reading frames 62 and 63 is replication competent and causes disease in the murine respiratory model.
An equine herpesvirus 1 (EHV-1) mutant was constructed by inserting a lacZ expression cassette into the intergenic region upstream of gene 62 (glycoprotein L; gL) and downstream of gene 63 (a homologue of the herpes simplex virus transcriptional activator ICP0). The recombinant lacZ62/63-EHV-1 had similar growth kinetics in cell culture to those of the parental wild type (wt) virus, with indistinguishable cytopathic effects and plaque morphology. Reverse transcriptase PCR confirmed that the lacZ insertion did not interfere with transcription of gL and immunoblot analysis indicated there was no modification to late gene expression as monitored by synthesis of EHV-1 glycoproteins C and D. The parental EHV-1 isolate HVS25A used here had almost identical nucleotide sequence to that published for isolate Ab4, in a 1200 bp region surrounding the insert, but lacked a HindIII site corresponding to Ab4 position 109,048. The lacZ62/63-EHV-1 caused respiratory disease in BALB/c mice with clinical signs, histopathology and virus titres in lungs throughout days 1-5 post infection similar to those induced by wt EHV-1. X-gal staining for beta-galactosidase expression in murine lungs clearly demonstrated EHV-1 infection in cells of the bronchiolar epithelium and pulmonary parenchyma, with a peak of infection evident at day 2 post infection, when up to 50% of bronchioles demonstrated blue-staining and thus virus-infected epithelial cells. The construction of this replication competent virus carrying a reporter gene identifies a site for insertion of foreign genes and will facilitate studies on the pathogenesis of EHV-1.


Investigations on immunogenicity of bovine fibrous connective tissue.
The immunogenicity of fibrous connective bovine tissue preserved by different methods was tested by a regional lymph node blastic cell reaction. The results were presented after transplantation of 10 experimental groups of grafts.


Mitral valve dynamics in severe aortic stenosis before and after aortic valve replacement.
The aortic and mitral valves are anatomically linked through a fibrous continuity. The investigators hypothesized that severe aortic stenosis (AS) would alter this fibrous continuity, affecting both the mitral valve and left ventricular function, and that mitral valve function would be altered after aortic valve replacement (AVR). The aim of this study was to evaluate the impact of AS and its treatment with surgical AVR on the mitral valve. Three-dimensional transesophageal echocardiography (using a Philips iE33 system) was performed on 49 patients: 20 controls with normal valves and left ventricular function, 20 with AS and normal left ventricular function studied before and after AVR, and nine with systolic heart failure and normal valves. Custom software tracked the aortic and mitral valves in three-dimensional space, allowing automated measurements of aortic and mitral annular (MA) morphology throughout the cardiac cycle. Patients with AS before AVR had reduced MA velocities. After AVR, aortic and MA areas were significantly smaller throughout the cardiac cycle compared with controls and pre-AVR values. MA displacement was reduced after AVR and in patients with systolic heart failure compared with those with AS and controls. Dynamic MA function is changed with AS and after AVR through alterations in the aortic-mitral fibrous continuity. The prosthetic valve ring results in reduced aortic and MA areas, which could affect blood flow in and out of the left ventricle. These changes suggest that the design of future prosthetic aortic valves should be more flexible to preserve the function of the aortic-mitral fibrous continuity.


Microbial diversity of vermicompost bacteria that exhibit useful agricultural traits and waste management potential.
Vermicomposting is a non-thermophilic, boioxidative process that involves earthworms and associated microbes. This biological organic waste decomposition process yields the biofertilizer namely the vermicompost. Vermicompost is a finely divided, peat like material with high porosity, good aeration, drainage, water holding capacity, microbial activity, excellent nutrient status and buffering capacity thereby resulting the required physiochemical characters congenial for soil fertility and plant growth. Vermicompost enhances soil biodiversity by promoting the beneficial microbes which inturn enhances plant growth directly by production of plant growth-regulating hormones and enzymes and indirectly by controlling plant pathogens, nematodes and other pests, thereby enhancing plant health and minimizing the yield loss. Due to its innate biological, biochemical and physiochemical properties, vermicompost may be used to promote sustainable agriculture and also for the safe management of agricultural, industrial, domestic and hospital wastes which may otherwise pose serious threat to life and environment.


Psychopharmacology of anticonvulsants: do all anticonvulsants have the same mechanism of action?
Anticonvulsants are not a single therapeutic class, but are composed of multiple distinct subclasses with different mechanisms of action, efficacies, and side effects.


[Prenatal treatment with magnesium sulphate: Initial clinical outcomes in pre-term infants less than 29 weeks and correlation with neonatal magnesium levels].
Antenatal magnesium sulphate (MgSO4) administration has shown to be effective in minimising cerebral palsy and severe motor dysfunction at the age of 2 years. The aim of this study is to analyse the initial clinical outcome of preterm neonates less than 29 weeks who have received prenatal MgSO4, as well as to determine the relationship between the magnesium dose delivered to the mother and the magnesium concentration in the neonates. A prospective cohort study was conducted on neonates of less than 29 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) of Hospital Universitario de Vigo from December 2012 to July 2015. Comparative analysis was performed on the perinatal outcomes, neonatal morbidity, mortality, and magnesium levels between the groups of neonates exposed to magnesium sulphate and the control group. A total of 42 neonates were included in the study. The mothers of 28 of them had received MgSO4 as a neuroprotective agent. Statistical significance was obtained in the mortality variable. There were no significant differences in the rest of studied variables. There was a significant correlation between the full dose of MgSO4 received by the mother and the levels of magnesium in the neonate in the first 24hours of life (r2 0.436; P<.001). A lower mortality was observed in the group that had been exposed to MgS04. No significant side effects were found as a result of administering of MgS04. The MgS04 dose received by mother has a linear relationship with the magnesium levels obtained in neonates.


Increased incidence of critical illness among patients with inflammatory bowel disease: a population-based study.
Little is known about how often, and for what reasons, patients with inflammatory bowel diseases (IBD) are admitted to the intensive care unit (ICU). We compared incidences of ICU admission, characteristics of critical illness, and mortality after ICU admission between patients with IBD and the general population. We identified all persons with IBD in the province of Manitoba using a validated administrative definition of IBD for the period from 1984 to 2010. Cases were considered incident for IBD if their first health system contact for IBD was in 1989 or later. We identified a population-based control group, matched by age, sex, and geography (based on postal code). Case and control cohorts were linked to the Manitoba ICU database. We compared outcomes between groups using age- and sex-standardized rates, Cox proportional hazards models, and logistic regression models, adjusting for age, sex, comorbidity, and socioeconomic status. There were 8224 prevalent and 4580 incident cases of IBD. After adjustment, the risk for ICU admission was higher for patients with IBD than controls (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.58-2.02). The risk of ICU admission was higher for patients with Crohn's disease (HR, 2.31; 95% CI, 1.95-2.75) than ulcerative colitis (HR, 1.37; 95% CI, 1.13-1.65). From 2000 through 2010, age- and sex-standardized annual incidence rates for ICU admission in the prevalent IBD cohort ranged from 0.55% to 1.12%. Compared with controls admitted to ICUs, 1 year after ICU admission, mortality was 32% among patients with IBD. Patients with IBD have a higher risk for admission to the ICU than the general population, and increased mortality 1 year after admission. These findings underscore the potential severity of IBD.


Incidence of clinically relevant psychiatric symptoms during glioblastoma treatment: an exploratory study.
In addition to neurological symptoms glioblastoma (GBM) patients can experience psychiatric complaints, which are often hard to recognize and difficult to treat. Research on psychiatric symptoms during glioblastoma treatment is limited, but can have significant impact on quality of life, treatment processes and even survival. The aim of this study is to explore the incidence of clinically relevant psychiatric symptoms, during glioblastoma treatment and active surveillance. Medical records of 302 GBM patients were reviewed from diagnostic surgery until discontinuation of treatment or active surveillance. Clinical relevance was defined as psychiatric symptoms that interfered with the oncological treatment and required referral to a psychiatrist. "Referred" versus "non-referred" GBM patients were compared using the Pearson Chi-Square test, Fisher's Exact Test or Mann Whitney-U test. Psychiatric symptoms occurred in 11.5% of patients during glioblastoma treatment or active surveillance, most often mood or behavioral symptoms, followed by psychotic symptoms. Referral occurred mainly during concomitant chemoradiation or adjuvant chemotherapy (64.3%). In 28.6% of patients psychiatric symptoms were thought to be attributive to medication. Treatment was discontinued in 17.9% of patients and temporarily interrupted in 3.6%. Possible risk factors included male gender, history of psychiatric disorder, postoperative delirium, non-frontal tumor location, anti-epileptic drug use at baseline and corticosteroid initiation during treatment. The found incidence of 11.5% and the high number of patients discontinuing treatment due to psychiatric symptoms justify more research in this, to date, understudied topic in scientific literature. Further prospective studies are needed to identify risk factors and unravel possible effects on survival.


SHARP: genome-scale identification of gene-protein-reaction associations in cyanobacteria.
Genome scale metabolic model provides an overview of an organism's metabolic capability. These genome-specific metabolic reconstructions are based on identification of gene to protein to reaction (GPR) associations and, in turn, on homology with annotated genes from other organisms. Cyanobacteria are photosynthetic prokaryotes which have diverged appreciably from their nonphotosynthetic counterparts. They also show significant evolutionary divergence from plants, which are well studied for their photosynthetic apparatus. We argue that context-specific sequence and domain similarity can add to the repertoire of the GPR associations and significantly expand our view of the metabolic capability of cyanobacteria. We took an approach that combines the results of context-specific sequence-to-sequence similarity search with those of sequence-to-profile searches. We employ PSI-BLAST for the former, and CDD, Pfam, and COG for the latter. An optimization algorithm was devised to arrive at a weighting scheme to combine the different evidences with KEGG-annotated GPRs as training data. We present the algorithm in the form of software "Systematic, Homology-based Automated Re-annotation for Prokaryotes (SHARP)." We predicted 3,781 new GPR associations for the 10 prokaryotes considered of which eight are cyanobacteria species. These new GPR associations fall in several metabolic pathways and were used to annotate 7,718 gaps in the metabolic network. These new annotations led to discovery of several pathways that may be active and thereby providing new directions for metabolic engineering of these species for production of useful products. Metabolic model developed on such a reconstructed network is likely to give better phenotypic predictions.


Quality control material for the detection of somatic mutations in fixed clinical specimens by next-generation sequencing.
Targeted next generation sequencing (NGS) technology to assess the mutational status of multiple genes on formalin-fixed, paraffin embedded (FFPE) tumors is rapidly being adopted in clinical settings, where quality control (QC) practices are required. Establishing reliable FFPE QC materials for NGS can be challenging and/or expensive. Here, we established a reliable and cost-effective FFPE QC material for routine utilization in the Ion AmpliSeq™ Cancer Hotspot Panel v2 (CHP2) assay. The performance characteristics of the CHP2 assay were determined by sequencing various cell line mixtures and 55 different FFPE tumors on the Ion Torrent PGM platform. A FFPE QC material was prepared from a mixture of cell lines derived from different cancers, comprising single nucleotide variants and small deletions on actionable genes at different allelic frequencies. The CHP2 assay performed with high precision and sensitivity when custom variant calling pipeline parameters where established. In addition, all expected somatic variants in the QC material were consistently called at variant frequencies ranging from 9.1 % (CV = 11.1 %) to 37.9 % (CV = 2.8 %). The availability of a reliable and cost-effective QC material is instrumental in assessing the performance of this or any targeted NGS assay that detects somatic variants in fixed solid tumor specimens.


A Placebo-Controlled Study to Assess the Sensitivity of Finger Tapping to Medication Effects in Parkinson's Disease.
Movement Disorder Society-Unified Parkinson's Rating Scale Part III (MDS-UPDRS III) is the gold standard for assessing medication effects in patients with Parkinson's disease (PD). However, short and rater-independent measurements would be ideal for future trials. To assess the ability of 3 different finger tapping tasks to detect levodopa/carbidopa-induced changes over time and to determine their correlation and compare their discriminatory power with MDS-UPDRS III. This was a randomized, double-blind, crossover study in 20 patients with PD receiving levodopa/carbidopa and placebo capsules after overnight medication withdrawal. Pre- and up to 3.5 hours postdose, MDS-UPDRS III and tapping tasks were performed. Tasks included 2 touchscreen-based alternate finger tapping tasks (index finger versus index-middle finger tapping) and a thumb-index finger task using a goniometer. In the alternate index finger tapping task, levodopa/carbidopa compared with placebo resulted in significantly faster (total taps: 12.5 [95% confidence interval, CI, 6.7-18.2]) and less accurate tapping (total spatial error: 240 mm [95% CI, 123-357 mm]) with improved rhythm (intertap interval standard deviation [SD], -16.3% [95% CI, -29.9% to 0.0%]). In the thumb-index finger task, tapping was significantly faster (mean opening velocity, 151 degree/s [64-237 degree/s]), with a higher mean amplitude (8.4 degrees [3.7-13.0 degrees]) and improved rhythm (intertap interval SD, -46.4% [95% CI, -63.7% to -20.9%]). The speed-related endpoints showed a moderate-to-strong correlation with the MDS-UPDRS III (r = 0.45-0.70). The effect sizes of total taps and spatial error in the alternate index finger tapping task and opening velocity in the thumb-index finger task were comparable with the MDS-UPDRS III. In contrast, the MDS-UPDRS III performed better than the alternate index-middle finger task. The alternate index finger and the thumb-index finger tapping tasks provide short, rater-independent measurements that are sensitive to levodopa/carbidopa effects with a similar effect size as the MDS-UPDRS III.


Simulated exposure of hospital emergency personnel to solvent vapors and respirable dust during decontamination of chemically exposed patients.
To ascertain the breathing-zone level of organic solvents and respirable particulates in a simulated hospital patient decontamination. An adult-sized, clothed plastic mannequin was contaminated with a solvent or particulate, then decontaminated. Rescuers were exposed to acetone, p-xylene, iron oxide, or zinc oxide during decontamination. We performed breathing-zone air sampling on the two rescuers. Five trials were run with each chemical. Two physicians performed the decontamination. Measured breathing-zone concentrations for the chemicals tested were significantly lower than their respective short-term breathing-zone limits (P = .042, .043, .001, and .001 for acetone, p-xylene, iron, and zinc oxide, respectively). The chemicals tested during simulated hospital decontamination did not pose a respiratory health risk to rescuers. This model may be useful in the extrapolation of breathing-zone exposure to more toxic chemicals. Because ours are preliminary data, the use of respiratory protective equipment during decontamination must be recommended.


["Mixed" and "miscellaneous" vulvovaginitis: diagnostics and therapy of vaginal administration of nystatin and nifuratel].
The evaluation of combined and miscellaneous vulvovaginal infections incidence and their treatment with combined vaginal products containing nifuratel and nystatin. Prospective study. Gynecologic outpatient department LEVRET, Prague; Laboratories of Microbiology AescuLab, Prague. 70 consecutive patients were examined with complaint of vaginal fluor and/or pruritus. We established macroscopic features of fluor, pH, amine test and mounts stained with Giemsa and Gram. We qualified the cases with more diagnostic criteria (mycosis, lactobacillosis, anaerobic vaginosis, aerobic vaginitis) as combined infection, those with no diagnostic criteria as miscellaneous. We treated all patients with vaginal tablets nystatin + nifuratel (Macmiror complex). We prescribed clotrimazol cream, if pruritus was present. We evaluated withdrawals of symptoms and relapses during 3 months after treatment. Combined infection was found in 21 patients from 70 (30%). The most frequent combination was that of mycosis and aerobic vaginitis (13/70, 18.6%) or mycosis and anaerobic vaginosis (4/70, 5.7%); 11 patients fulfilled criteria of no diagnosis. We concluded them as "miscelaneous". The treatment was successful in all cases, 10 women relapsed in 3 months. Combined vaginal infection findings are present very often (30%), likewise miscellaneous ones (15%) occur. The treatment of these women in successful with vaginal tablets with nystatin + nifuratel.


Spontaneous phagocytosis of C-type synaptic terminals by spinal alpha-motoneurons in newborn kittens. An electron microscopic study.
The cell bodies and proximal dendrites of spinal alpha-motoneurons were studied electron microscopically with the aid of serial sections during the first postnatal week in the cat. The observations suggested that some of the synaptic terminals of the so-called C-type on the cell bodies and dendrites are phagocytosed by the motoneurons during the first few days after birth. This finding is discussed in relation to the earlier demonstrated postnatal loss of synaptic terminals on the motoneurons after birth and differences demonstrated between different functional types of spinal motoneurons with respect to the number and distribution of C-type terminals in the adult cat.


Sex- and age-related changes in bone and serum osteocalcin.
We measured bone osteocalcin concentrations in EDTA extracts from iliac crest cortical bone specimens obtained postmortem from 63 men and 71 women (age range 19-90 years), and serum osteocalcin levels in healthy blood donors, 49 men and 49 women (age range 21-65 years). Bone and serum osteocalcin concentrations were higher in men than in women, and an age-related decline was observed in both sexes. In women, however, a temporary increase in serum (P less than 0.05) osteocalcin was seen in the sixth decade. This study shows sex- and age-related changes in bone osteocalcin consistent with changes in serum osteocalcin, confirming that serum measurement of osteocalcin reflects bone levels. As osteocalcin reflects osteoblastic activity and thus bone formation, the overall decline in bone and serum osteocalcin in men and women, and the increase in serum osteocalcin in the sixth decade in women, indicate that aging is associated with a decrease in bone formation and turnover and that osteoblastic activity and bone turnover are stimulated at the menopause.


Comparative study of the combustion, pyrolysis and gasification processes of Leucaena leucocephala: Kinetics and gases obtained.
Leucaena leucocephala is a fast-growing leguminous biomass with great energetical and value-added chemical compounds potential (saccharides, biogas, bio-oil, etc.). Using the thermogravimetric and derivative thermogravimetric curves, the different trends followed by L. leucocephala during pyrolysis, 0.25 equivalence ratio (ER) of gasification, 0.50 equivalence ratio of gasification and combustion were analyzed, and the activation energies were obtained by Distributed Activation Energy Model (DAEM) method. Gas samples were collected through adsorption tubes during the gasification at 0.25 ER and 0.50 ER to observe the distribution of the main chemical products in this process by gas chromatography/mass spectrometry and were compared with pyrolysis products. It was found that small amounts of oxygen have changes in the kinetics of the process, leading to significant decreases in the activation energy at the beginning of the degradation of components such as cellulose (from 170 to 135 kJ mol-1 at 0.25 conversion at 0.50 ER gasification). The activation energy of lignin disintegration was also reduced (342 kJ mol-1), assimilating the beginnings of gasification processes such as the Boudouard reaction. 0.50 ER gasification is potentially an interesting process to obtain quality bio-oil, since a large amount of hexane is detected (44.96%), and value-added oxygenated intermediates such as alcohols and glycols. Gasification at 0.25 ER, on the other hand, is much more similar to pyrolysis, obtaining a wide variety of short-chain compounds resulting from the disintegration of the main lignocellulosic components, especially ketones such as 1-hydroxypropan-2-one (19.48%), and notable amount of furans and anhydrosugars like d-allose (5.50%).


Obesity, rather than high fat diet, exacerbates the outcome of influenza virus infection in influenza-sensitized mice.
Obesity is associated with impaired immune function and increased susceptibility to infection. High fat (HF) diet-induced obesity is a commonly used animal model. However, HF diet itself is known to affect immune function and infection. Thus, it is not discernable which one, HF diet or adiposity, is the major contributor to the observed impairment in immunity and susceptibility to infection in HF diet-induced obesity. We hypothesized that obesity is a major contributor to impaired immune function. Weight-matched outbred female CD-1 mice (1-mo) were randomly assigned to either a HF (45%) or a low fat (LF, 10%) diet group. Ten week after feeding their respective diets, weight gain in the mice fed the HF diet varied greatly. Thus, based on the average body weight, mice in HF diet group were divided into two sub-groups: HF lean (HF-L) and HF obese (HF-O). After 25-week, mice were immunized with an influenza A/Puerto Rico/8/34 vaccine and boosted 3-week later. Five week after the booster, mice were infected with influenza A/Puerto Rico/8/34 virus, and body weight was recorded daily for 1 month. HF-O mice exhibited significant weight loss after influenza virus challenge compared to LF and HF-L mice while LF and HF-L mice largely maintained their weight to a similar extent. Our findings suggest that obesity, rather than HF diet, per se, may impair the efficacy of influenza vaccination.


Infection rate of Opisthorchis viverrini metacercariae in cyprinoid fish from the markets and its association to human opisthorchiasis in the local community in the Northeast Thailand.
The prevalence of Opisthorchis viverrini, a fish-borne zoonotic trematode that can provoke cholangiocarcinoma, is high in the Northeast Thailand. The aim of this study was to determine the prevalence of O. viverrini metacercariae in the cyprinid fish and determine its association of O. viverrini infection among the consumers who regularly buy fish in the markets. A cross-sectional study was conducted in nine provinces covering 20 districts of Thailand, and we examined 778 cyprinoid fish specimens belonging to five species purchased from local markets. Pepsin-HCl digestion method was used to recover O. viverrini metacercariae from fish. In all districts surveyed, O. viverrini metacercariae-positive fish were found with the infection rates ranging from 3.9 to 21.1%. All five fish species studied were positive for O. viverrini metacercariae: Henicorhynchus siamensis (13.7%), Cyclocheilichtys spp. (12.7%), Hampala spp. (8.1%), Systomus spp. (6.9%) and Barbonymus goniatus (5.0%). An average prevalence of O. viverrini infection was 7.1% in the fish consumers surveyed in the markets. The source of fish was determined and our results showed that parasitized fish are sold in markets up to 100 km away from the point of capture, which contributes to the dispersion and maintenance of this helminthiasis. Our results point to the transmission of liver flukes via markets, in spite of many active programs of health education, elimination, prevention and control aimed to reduce O. viverrini infection and subsequent cholangiocarcinoma in the endemic areas of Thailand.


Advances into Understanding the Vital Role of the Mitochondrial Citrate Carrier (CIC) in Metabolic Diseases.
The mitochondrial citrate carrier (CIC) is a nuclear-encoded protein located in the inner mitochondrial membrane. By mediating efflux of citrate from the mitochondria to the cytosol, CIC links mitochondrial central carbon metabolism and cytosolic lipogenesis together. Abnormal activity or expression of CIC was found in cancers, developmental disorders and many other diseases. Recently, the specific inhibitors of CIC were proved to modify basic cellular metabolism, which in turn led to changes in disease course such as reverted steatohepatitis and cancer cell death. CIC is believed to be a key player and may serve as a novel therapeutic target in types of human metabolic diseases. Therefore, in this paper, we integrally described the structure and function of CIC. Then, we gave an overview of CIC related diseases including cancers, congenital diseases, pro-inflammatory effects and some other diseases. At the same time, the potential molecular mechanisms of CIC in the above diseases were illuminated. Finally, we illuminated some emerging areas for future investigation.


Nutritional implications of chronic dyspepsia in childhood.
Chronic dyspepsia is common in children. However, the association of individual predominant symptoms with gastric emptying and their impact on nutritional status are poorly defined. We therefore studied 31 children (mean age 11 years, 14 boys) with chronic dyspepsia and classified their predominant symptoms (PS) by their character and severity. Gastric emptying (GE) T(1/2) of a solid meal was carried out in all patients, while upper gastrointestinal endoscopy was done in the treatment failures. All patients received two months treatment with cisapride. Weight for age z scores were recorded before and three months after treatment. There were 12 patients with epigastric pain (EP) as the PS (7 moderate/severe). Postprandial fullness (PF) was the PS in 19 patients (12 moderate/severe). GE T(1/2) was prolonged and weight for age z scores were lower in children who had moderate/severe (but not mild) PF comparing to those who had EP (P < 0.0001 and P = 0.003, respectively). A significant improvement in weight was observed in the same group alone following treatment with cisapride (P = 0.0003). In conclusion, impaired GE is common in dyspeptic children with PF and have adverse effects on nutritional status.


Abiotic and biotic factors influencing the winter distribution of predatory insects.
Various environmental factors were investigated to analyse those involved in successful overwintering and possibly overwintering site selection for Tachyporus hypnorum and Demetrias atricapillus, both important coleopteran predators of cereal aphids. The results of the study indicated food supply to be important for both predator species during the winter period, although the role of biotic factors in site selection in the autumn could not be clearly demonstrated. The winter distribution of the two species could, however, be explained well in terms of abiotic factors. It is suggested that these and other similar predator species have well-defined overwintering requirements and that these can be exploited in the management of field boundary habitats.


Elution and disinfection of silver and zinc nanoparticles in co-fired ceramic water filters.
Ceramic water filters (CWFs) are decentralized water treatment technologies commonly used in resource-restricted geographies. Inclusion of silver nanoparticles (AgNP) assists with disinfection but can substantially increase costs. This research investigates AgNP supplementation with zinc oxide (ZnO) as a low-cost bactericide alternative. CWF disks were impregnated with varying AgNP and/or ZnO concentrations and challenged against Escherichia coli. Effluent bacteria were enumerated and monitored over 72 h while eluted metal concentrations were measured and scaled according to surface area to establish 'pot-equivalent' estimates (0-50 ppb Ag and 0-1200 ppb Zn). Ag addition correlated to subsequent measured release values, though Zn impregnation did not. Background Zn was thus evidently present. Meanwhile, the eluted metal concentration related to disinfection: a CWF with a pot-equivalent elution estimate of 2 ppb Ag and 156 ppb Zn achieved a Log Removal Value (LRV) of 2.0 after 60 min of filtration and 1.9 after 24 h of storage while a CWF with a pot-equivalent elution estimate of 20 ppb Ag and 376 ppb Zn achieved LRVs of 3.1 and 4.5 after the same filtration and storage times, respectively. Clay elemental composition may therefore impact filter performance more than previously considered This trend was further confirmed by batch experiments with Ag and Zn in concentrations of 0-20 ppb Ag and 0-800 ppb Zn, respectively: bacterial regrowth was only observed when Ag and Zn were each below 5 ppb and 160 ppb while 1 ppb Ag and 800 ppb Zn maintained complete disinfection for 72 h. Increased Zn concentrations thus reduced Ag required to maintain disinfection over time. Overall, it is recommended to include Zn with Ag for CWF to improve short-term and long-term disinfection efficacy and associated water safety.


"Better the devil you know": Are stated preferences over health and happiness determined by how healthy and happy people are?
Most people want to be both happy and healthy. But which matters most when there is a trade-off between them? This paper addresses this question by asking 4000 members of the UK and US public to make various choices between being happy or being physically healthy. The results suggest that these trade-offs are determined in substantial part by the respondent's own levels of happiness and health, with unhappy people more likely to choose unhappy lives and unhealthy people more likely to choose unhealthy ones: "better the devil you know, than the devil you don't". Age also plays an important role; older people are more likely to choose being healthy over being happy. Information about adaptation to physical health conditions matters too, but less so than respondent characteristics. These results further our understanding of public preferences with important implications for policymakers concerned with satisfying those preferences.


Computerized brain tomography measures compared with spontaneous and suppressed plasma cortisol levels in major depression.
We determined brain density and ventricular measurements with computerized tomography (CT) in 33 depressed patients and compared the results with basal plasma cortisol and its suppressibility by dexamethasone. Mean plasma cortisol was positively related to elevated ventricular brain ratio (VBR). No association could be found between dexamethasone suppression test (DST) status and VBR or any other CT parameter. Elevated plasma cortisol levels and increased VBRs were positively correlated with total scores on the Brief Psychiatric Rating Scale, the Global Assessment Scale and the Bech-Rafaelsen Melancholia Scale, but they were not significantly correlated with total score on the Hamilton Anxiety Scale.


Perinatal dexamethasone-induced alterations in apoptosis within the hippocampus and paraventricular nucleus of the hypothalamus are influenced by age and sex.
Exposure to high levels of glucocorticoids (GCs) during development leads to long-term changes in hypothalamic-pituitary-adrenal (HPA) axis regulation, although little is known about the neural mechanisms that underlie these alterations. In this study, we investigated the effects of late gestational (days 18-22) or postnatal (days 4-6) administration of the GC receptor agonist dexamethasone (DEX) on an apoptosis marker in two brain regions critical to HPA axis regulation, the hippocampus and the hypothalamic paraventricular nucleus (PVN). One day after the final DEX injection, male and female rats were sacrificed, and brains were processed for immunohistochemical detection of cleaved caspase-3, an apoptotic cell death indicator. DEX increased cleaved caspase-3 immunoreactivity in the CA1 hippocampal region of both sexes following prenatal but not postnatal treatment. Prenatal DEX also increased caspase-3 immunoreactivity in the CA3 region, an elevation that tended to be greater in females. In contrast, postnatal DEX resulted in a much smaller, albeit significant, induction in CA3 caspase-3 compared with prenatal treatment. Quantitative real-time PCR analysis revealed that prenatal but not postnatal DEX-induced hippocampal cleaved caspase-3 correlated with elevated mRNA of the proapoptotic gene Bad. Few caspase-3-ir cells were identified within the PVN regardless of treatment age, although postnatal but not prenatal DEX increased this number. However, the region immediately surrounding the PVN (peri-PVN) showed significant increases in caspase-3-ir cells following pre- and postnatal DEX. Together these findings indicate that developmental GC exposure increases apoptosis in HPAaxis-associated brain regions in an age- and sex-dependent manner.


Immunoconcentration of Shiga toxin-producing Escherichia coli O157 from animal faeces and raw meats by using Dynabeads anti-E. coli O157 and the VIDAS system.
To identify the reservoirs and routes of transmission of Shiga toxin-producing Escherichia coli (STEC) O157, sensitive detection and isolation methods are necessary. The sensitivity of traditional culture methods can be improved significantly by the inclusion of an immunoconcentration step, resulting in less false-negatives. In this report, we evaluated the results of two commercially available test systems: Dynabeads anti-E. coli O157 and the Vitek Immunodiagnostic Assay System (VIDAS) Immuno-Concentration E. coli O157 (ICE) kit. Additionally, we compared two selective isolation media for STEC O157. Statistical analysis of the results obtained for animal faecal samples (n=637) examined by both immunoconcentration methods showed that by the manual Dynabeads anti-E. coli O157 procedure systematically more samples were identified as positive than by the VIDAS ICE. In case of meat samples (n=360), no difference between the results of the two methods was found. In addition to being accurate, the Dynabeads anti-E. coli O157 method is a less expensive method than the VIDAS ICE. But, the Dynabeads method is laborious and there is a risk of cross-contamination. The VIDAS ICE procedure on the other hand is fully automated with a standardised performance; fast and safe for the user. Irrespective of the type of sample (faeces or meat) and the immunoconcentration technique applied (Dynabeads anti-E. coli O157 or VIDAS ICE) more samples were found positive after plating onto CHROMagar O157 with cefixime (0.025 mg l(-1)) and tellurite (1.25 mg l(-1)) than after plating onto sorbitol-MacConkey agar with cefixime (0.05 mg l(-1)) and tellurite (2.5 mg l(-1)). However, only in case of meat samples examined by the VIDAS ICE the difference between the isolation media was not statistically significant.


Assessing the Acceptability of a Co-Produced Long COVID Intervention in an Underserved Community in the UK.
The COVID-19 pandemic has disproportionately affected people from more deprived communities. The experience of Long COVID is similarly distributed but very few investigations have concentrated on the needs of this population. The aim of this project was to co-produce an acceptable intervention for people with Long COVID living in communities recognised as more deprived. The intervention was based on a multi-disciplinary team using approaches from sport and exercise medicine and functional rehabilitation. The co-production process was undertaken with a stakeholder advisory group and patient public involvement representation. This study identified participants by postcode and the indices of multiple deprivation (IMD); recruitment and engagement were supported by an existing health and wellbeing service. A virtual 'clinic' was offered with a team of professional practitioners who met participants three times each; to directly consider their needs and offer structured advice. The acceptability of the intervention was based on the individual's participation and their completion of the intervention. Ten participants were recruited with eight completing the intervention. The partnership with an existing community health and wellbeing service was deemed to be an important way of reaching participants. Two men and six women ages ranging from 38 to 73 were involved and their needs were commonly associated with fatigue, anxiety and depression with overall de-conditioning. None reported serious hardship associated with the pandemic although most were in self-employment/part-time employment or were not working due to retirement or ill-health. Two older participants lived alone, and others were single parents and had considerable challenges associated with managing a household alongside their Long COVID difficulties. This paper presents the needs and perspectives of eight individuals involved in the process and discusses the needs and preferences of the group in relation to their support for self- managed recovery from Long COVID.


Fluoride removal using a chelating resin containing phosphonic-sulfonic acid bifunctional group.
S9570-Fe(III), a modified chelating resin containing sulphonated monophosphonic acid bifunctional groups, was used for the fluoride removal from aqueous phase for the first time. The results specified that S9570-Fe(III) exhibited better adsorption towards the fluoride ions as compared to the other commonly used chelating resins having monofunctional group such as iminodiacetic acid, sulfonic acid or carboxylic acid. Adsorption thermodynamic and kinetic studies of S9570-Fe(III) chelating resin for the fluoride also have been carried out. The thermodynamic results demonstrated that the adsorption was a spontaneous process accompanied with a gradual decrease in entropy and the low temperature was favorable for the fluoride ion adsorption. The kinetic experiments showed that the resin exhibited a rapid initial adsorption behavior and the adsorption process more complied with the pseudo-second order reaction model which indicating that the whole adsorption process was controlled by a combined mechanism of intraparticle diffusion and chemical sorption. Adsorption mechanism of S9570-Fe(III) resin for fluoride ions was predicted. The study demonstrated the effectiveness of the phosphoric-sulfonic acid bifunctional group chelating resin to remove fluoride, and provided a novel type removal method for the fluoride.


Microplastics and other emerging contaminants in the environment after COVID-19 pandemic: The need of global reconnaissance studies.
Evidence of the increase of emerging contaminants in the environment due to the COVID-19 pandemic, such as personal protective equipment (PPE), disinfectants, pharmaceuticals, etc., has enlarged. Here we explain the variety of pathways of these emerging contaminants to enter the environment, including wastewater treatment plants, improper disposal of PPE, and runoff from surfaces treated with disinfectants. We also discuss the current state-of-art of the toxicological implications of these emerging contaminants. Initial research suggests that they may have harmful effects on aquatic organisms and human health. Future directions are suggested as further research is needed to fully understand the impacts of these contaminants on the environment and humans, as well as to develop effective approaches to mitigate their potential negative effects.


Maternal predictors of RBC folate levels in an urban Canadian population.
To assess factors associated with low Red Blood Cell folate (RBCf) levels in an obstetric population in a tertiary centre. Cross-sectional study. Three hundred and fifty women completed a questionnaire detailing use of folic acid supplementation, and had their RBCf levels measured. Values ≥ 906 nmol/L were considered optimal. Factors associated with optimal RBCf were assessed, individually and in a logistic regression model. Median RBCf was 1282 nmol/L. Thirty-five women (10%) had suboptimal levels. Predictors of suboptimal RBCf were non-Caucasian ethnicity, non-consumption of folic acid supplementations, and inadequate health care provider information regarding the benefits of folic acid consumption. Although, in our population, a high proportion of women achieved optimal levels of RBCf, some women remain at risk due to inadequate folate consumption. Patient and health care provider education regarding folate can still be improved, particularly in the groups identified to be at greater risk.


Hypoplastic left heart syndrome, cor triatriatum and partial anomalous pulmonary venous connection: Imaging of a very rare association.
A newborn is presented with an association of hypoplastic left heart syndrome, cor triatriatum and partial anomalous pulmonary venous connection. The diagnosis was established with echocardiography and further confirmed with computed tomography. To our knowledge the images of such an association have never been reported before.


Prevalence of cardiac involvement in home-based recovered coronavirus disease 2019 (COVID-19) patients: a retrospective observational study.
Coronavirus disease 2019 (COVID-19) has a risk of cardiac arrhythmia, acute coronary syndrome, heart failure and myocarditis, and the prognosis of COVID-19 has been associated with cardiovascular symptoms. However, there has not been enough information about cardiovascular involvement in patients who had recovered home-based mild symptoms of COVID-19 infection. Therefore, this study evaluates the prevalence of cardiac involvement and associated factors in home-based recovered COVİD-19 patients. A total of 64 participants who applied to cardiology outpatient clinics with cardiac symptoms after recovering from COVID infection were recorded between April and December 2020. The patients were divided into two according to cardiovascular involvement in the cardiovascular magnetic resonance (CMR) imaging results. No significant difference between the two groups regarding age and co-morbidities. Patients with cardiac involvement had higher C-reactive protein compared to without cardiac involvement patients. A total of 46 patients who recently recovered from COVID-19 had abnormal CMR findings such as myocardial late gadolinium enhancement or pericardial enhancement. In addition, the left ventricular ejection fraction and stroke volume were significantly lower in the cardiac involvement patients. We demonstrate cardiac involvement in 46 patients (71%) with recent COVID-19, independent of pre-existing conditions. This indicates that there may be widespread cardiac involvement without high troponin values or severe clinical symptoms.


Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.
The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.


Comparative proteomics revealed duodenal metabolic function associated with feed efficiency in slow-growing chicken.
The Korat chicken (KR), developed in Thailand, is a slow-growing breed developed as an alternative breed for Thai chicken producers. The growing interest in slow-growing chicken meat, due to its unique taste, distinct texture, health benefits, and higher broiler welfare have led to higher market demand for KR. However, its low feed efficiency (FE) has a significant negative impact on farm profitability. Understanding the molecular mechanism regulating FE allows for designing a suitable selection program and contributing to breeding more efficient chicken for poultry production. Thus, the objective of our study was to investigate the proteome differences and possible pathways associated with FE in male KR using a label-free quantitative proteomic approach. Seventy-five KR males were individually evaluated for FE, and duodenum samples from 6 animals (3 high-FE and 3 low-FE chickens) were collected at 10 wk of age for differential abundant proteins (DAPs), protein networks, functional enrichment, and pathway analyses. In this study, we found 40 DAPs significantly associated with FE pathways, including glycolysis/gluconeogenesis, peroxisome, oxidative phosphorylation, tight junction, and cysteine and methionine metabolism. Thus, variations in observed DAPs or genes related to DAPs could be interesting biomarker candidates for selection for higher feed utilization efficiency in chicken.


The follow-up of renal transplant recipients by telephone consultation: three years experience from a single UK renal unit.
Although telephone consulting is increasingly used by clinicians seeking to balance rising caseloads, heightened patient expectation and the desire to ensure continued improvements in the quality, convenience and accessibility of the care they provide, its use to provide care to renal transplant recipients has not previously been described. Climate change is a major global public health threat. However, the provision of healthcare itself has a significant environmental impact. A transformation to lower carbon clinical care must be achieved without detriment to the quality of the patient care. This article reports the use of telephone consultation clinics to provide follow-up to renal transplant recipients over a three-year period. The benefits of this service to patients, providers and the environment are outlined, the existing literature regarding the provision of virtual care to patients with kidney disease is reviewed, and the possibilities of more widespread adoption are discussed.


Characterization of the microbiota of commercially traded finfish fillets.
The profile of human gut microbiota is known to be affected by diet and is linked to human health. Seafood is a highly consumed food and it accounts for a large proportion of food-borne illness. The objective of this study is to characterise the microbiota of fish fillets of various species sold in the Canadian market. We test 19 fish fillet samples from nine species in five fish families, ten of which were previously determined to be mislabeled as different species. The microbiota profiles were characterized using 16S rRNA gene high-throughput sequencing. Despite the complexities of the supply chain to produce these fillets, the major microbial groups were fairly consistent across samples. Significant differences in microbial taxa were observed between species, families, and based on labelling accuracy. Several putative spoilage and putative pathogenic taxa were identified. Studying food-associated microbiota can provide comprehensive information on food safety, authenticity, and traceability.


[Analysis of chromatic value of gingival porcelain].
To study the distribution of the chromatic value of gingival porcelains. The color change of Shofu VINTAGE and Vita VMK95 gingival porcelains on the black and white backings was determined with a spectrophotometer (PR-650). The results showed that the chromatic value of gingival porcelains was different on varying backings. The color space of gingival porcelain was L*: 41.85 - 50.64, a*: 12.46 - 19.46, b*: 1.33 - 4.62. The chromatic value distribution cannot cover the color region of natural gingiva.


Relationship between bullet diameter and bullet defect diameter in human calvariums.
Existing literature on the relationship between bullet diameter and bullet defect diameter in the human calvarium is summarized and discussed. The hypothesis, derived from the literature, that bullet deformation influences bullet defect diameter was studied in a small controlled experiment. The mean defect size caused by non-deforming projectiles was found to be smaller than the mean defect size caused by deforming projectiles of equal original mass and size. The p value of the difference between the two means, measured in two different ways, was found to be 0.002 for both in a Mann-Whitney U test and was significant if the confidence level is set at 5%.


The joint hierarchical structure of adolescent personality pathology: converging evidence from two approaches to measurement.
To examine the joint hierarchical structure of two measures of adolescent personality pathology within a community sample of Canadian adolescents. Self-reported data on demographic information and pathological personality traits were obtained from 144 youth (M age = 16.08 years, SD = 1.30). Personality pathology was measured using the youth-version of the Schedule for Nonadaptive and Adaptive Personality (SNAP-Y; Linde, Stringer, Simms, & Clark, in press) and the Dimensional Personality Symptom Item Pool (DIPSI; De Clercq, De Fruyt, Van Leeuwen, & Mervielde, 2006). Lower-order scales were subjected to structural hierarchical analyses. Scales from the two measures were complementary in defining higher-order traits. Traits at the 4-factor level of the hierarchy (Need for Approval, Disagreeableness, Detachment, and Compulsivity) showed similarities and differences with previous results in adults. The current investigation integrated top-down and bottom-up measures for a comprehensive account of the higher-order hierarchy of adolescent personality pathology. Results are discussed in the context of convergence across approaches and in comparison with previous findings in adult samples.


[Extrapulmonary tuberculosis].
Extrapulmonary tuberculosis represents an increasing proportion of all cases of tuberculosis reaching 20 to 40% according to published reports. Extrapulmonary TB is found in a higher proportion of women, black people and immunosuppressed individuals. A significant proportion of cases have a normal chest X-Ray at the time of diagnosis. The most frequent clinical presentations are lymphadenitis, pleuritis and osteoarticular TB. Peritoneal, urogenital or meningeal tuberculosis are less frequent, and their diagnosis is often difficult due to the often wide differential diagnosis and the low sensitivity of diagnostic tests including cultures and genetic amplification tests. The key clinical elements are reported and for each form the diagnostic yield of available tests. International therapeutic recommendations and practical issues are reviewed according to clinical presentation.


Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations.
Nephropathic cystinosis is an inherited lysosomal transport disorder caused by mutations in the CTNS gene that encodes for a lysosomal membrane transporter, cystinosin. Dysfunction in this protein leads to cystine accumulation in the cells of different organs. The accumulation of cystine in the kidneys becomes apparent with renal tubular Fanconi syndrome between 6 and 12 months of age and leads to renal failure in the first decade of life. The aim of this study was to analyze the CTNS mutations in 20 Iranian patients, from 20 unrelated families, all of whom were afflicted with infantile nephropathic cystinosis. In these patients, seven different mutant alleles were found, including two new mutations, c.517T>C; p.Y173H and c.492_515del, that have not been previously reported. In addition, we observed that c.681G>A, the common Middle Eastern mutation, was the most common mutation in our patients. Moreover, a new minisatellite or variable number of tandem repeat marker (KX499495) was identified at the CTNS gene. Seven different alleles were found for this marker, and its allele frequency and heterozygosity degree were calculated in cystinosis patients and healthy individuals.


A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage.
Nimodipine is the only drug approved for use by the Food and Drug Administration for improving outcome after aneurysmal subarachnoid hemorrhage (SAH). It has less than optimal efficacy, causes dose-limiting hypotension in a substantial proportion of patients, and is administered enterally 6 times daily. We describe development of site-specific, sustained-release nimodipine microparticles that can be delivered once directly into the subarachnoid space or cerebral ventricles for potential improvement in outcome of patients with aneurysmal SAH. Eight injectable microparticle formulations of nimodipine in poly(DL-lactide-co-glycolide) (PLGA) polymers of varying composition were tested in vitro, and 1 was advanced into preclinical studies and clinical application. Intracisternal or intraventricular injection of nimodipine-PLGA microparticles in rats and beagles demonstrated dose-dependent, sustained concentrations of nimodipine in plasma and cerebrospinal fluid for up to 29 days with minimal toxicity in the brain or systemic tissues at doses <2 mg in rats and 51 mg in beagles, which would be equivalent of up to 612-1200 mg in humans, based on scaling relative to cerebrospinal fluid volumes. Efficacy was tested in the double-hemorrhage dog model of SAH. Nimodipine-PLGA microparticles significantly attenuated angiographic vasospasm. This therapeutic approach shows promise for improving outcome after SAH and may have broader applicability for similar diseases that are confined to body cavities or spaces, are self-limited, and lack effective treatments.


Carboxymethylsulfonylated Ribopyrimidines: Rational Design of Ribonuclease A Inhibitors Employing Chemical Logic.
Hydrolysis of RNA by ribonuclease A crucially depends on the participation of the 2'-OH group as well as the positioning of the internucleotide bond at two different sites of the enzyme. Therefore, ribopyrimidines were modified with -SO2CH2CO2H, an acidic functional group, which was expected to interact with the phosphate binding site. These ribonucleosides were designed to understand the influence of the 2'-OH group of these inhibitors on ribonuclease A inhibition along with the effect of the -SO2CH2CO2H group. The "down" configuration of the 2'-OH group enhanced the inhibitory properties (Ki =1.75 μm) and also imparted important Val43 H-bonding with the furanose oxygen atom of the inhibitors. One of the most important aspects of this work is that there was no serendipitous discovery of the inhibitors. The inhibitors reported in this manuscript were obtained by design by employing chemical logic.


The inhibitory effects of rebamipide on cigarette smoke-induced airway mucin production.
Cigarette smoke may be the main cause of chronic bronchitis. Exposure of cigarette smoke induces the recruitment of inflammatory cells in the airway epithelium, and release of the tumor necrosis factor alpha (TNFalpha) from airways. Previous reports have shown that cigarette smoke induces goblet cell metaplasia by activating an epidermal growth factor receptor (EGFR) cascade, and that this results in mucin production. Rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, OPC-12759) directly inhibits the production of superoxide (O2-) and inhibits proinflammatory cytokines (such as TNFalpha and IL-8). In the present study, we aimed to analyze the inhibitory effects of rebamipide on TNFalpha and EGFR activation after cigarette smoke treatment in vitro and in vivo. NCl-H292 cells and Sprague-Dawley rats were used for in vitro and in vivo studies. In vitro studies, cigarette smoke solution was found to increase TNFalpha secretion, and EGFR-specific tyrosine phosphorylation, and to elevate MUC5AC production. These effects were inhibited dose-dependently by pretreatment with rebamipide (MUC5AC protein levels were inhibited from 44% to 17%, P<0.05). In vivo studies, cigarette smoke was found to cause inflammatory cell recruitment and to increase the secretion of TNFalpha in bronchoalveolar lavage (BAL) fluids (from 198+/-78 to 2270+/-158 pg/ml, P<0.01). Moreover, the pretreatment of rats with rebamipide inhibited goblet cell metaplasia and TNFalpha secretion, dose-dependently (from 2270+/-158 to 1377+/-112 pg/ml, P<0.05). In conclusion, the exposure of airway epithelium to cigarette smoke-induced TNFalpha production, neutrophil recruitment, activated EGFR, and caused MUC5AC mucin synthesis. Moreover, rebamipide was found to prevent this cigarette smoke-induced TNFalpha release, and mucin production.


Double tumor of the larynx: a case report.
A case is described of a double laryngeal tumor with simultaneous evolution but different histological patterns: a chondrosarcoma and an epidermoid carcinoma "in situ" involving both vocal cords. To our knowledge, only one previous case has been reported in the literature.


Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels.
Ion channels gated by neurotransmitters are present across metazoans, in which they are essential for brain function, sensation and locomotion; closely related homologs are also found in bacteria. Structures of eukaryotic pentameric cysteine-loop (Cys-loop) receptors and tetrameric ionotropic glutamate receptors in multiple functional states have recently become available. Here, I describe how these studies relate to established ideas regarding receptor activation and how they have enabled decades' worth of functional work to be pieced together, thus allowing previously puzzling aspects of receptor activity to be understood.


Pattern recognition receptors and differentiation antigens define murine myeloid cell heterogeneity ex vivo.
Recruitment of myeloid cells during inflammatory reactions plays an important role in the propagation and resolution of inflammation. However, the identification and characterization of these cells in mice has been hampered by cellular heterogeneity at the functional and phenotypic level. We have defined criteria for the rapid flow-cytometric identification of monocytes (M(o)), macrophages (MPhi), neutrophils (N(eu)) and eosinophils (E(os)) in murine tissues using novel and established myeloid markers. These criteria were applied to the study of naive mice and mice with experimentally induced inflammation, both local and systemic, and also to a murine model of tumor progression. We show that the murine 7/4 antigen and the beta-glucan receptor, Dectin-1, are particularly useful for the sub-division of myeloid cells into individual populations, even when inflammatory conditions modulate their surface expression. Furthermore, 7/4 expression allows distinction between M(o) recently recruited to a site and the resident cells already present. These studies highlight the heterogeneity of the murine M(o)/MPhi-lineage, define an extended phenotype for murine myeloid cells and greatly facilitate the ex vivo characterization of these cells during very different models of inflammation.