Anti-HCV IgG avidity index in acute hepatitis C.
The diagnosis of acute hepatitis C (AHC) is based on seroconversion to positive anti-HCV, which is usually not clinically possible. To determine if avidity of anti-HCV IgG can be used for the diagnosis of AHC infection. We enrolled 40 consecutive patients with AHC, 16 drug addicts (IVDA) with exacerbation of chronic hepatitis C (IVDA e-CHC group), 21 non-IVDA with exacerbation of chronic hepatitis C (IVDA-free e-CHC group) and 40 with chronic hepatitis C (CHC group). HCV avidity index (HCV-AI) was determined by ELISA on sera pre-diluted 1:10 with 1M guanidine. On admission, HCV-AI values were significantly lower in the AHC group (mean+/-S.D.: 0.50+/-0.30) than in IVDA-free e-CHC group (0.97+/-0.08, p<0.0001), IVDA e-CHC group (0.90+/-0.29, p<0.0001) or CHC group (1.06+/-0.20, p<0.0001). An HCV-AI lower than 0.7 obtained within the 8th day of illness distinguished patients with AHC infection from the IVDA-free e-CHC cases. An increase in HCV-AI was observed in 24 (72.7%) of 33 in AHC group, in none of 13 in IVDA-free e-CHC group and in 3 (27.3%) of 11 in IVDA e-CHC group. HCV-AI is useful in identifying AHC infection in patients observed within the 8th day from the onset of symptoms.


Evaluation of Specific Administering Devices for Antineoplastic Drugs Compounded in Syringes in Paediatry: Methodology Proposal.
Purpose The aims of this study were to propose a simple methodology to assess the rinsing volume of syringe extension sets and to compare several marketed devices. Methods A UV-spectrophotometry assay using quinine hydrochloride as drug substitute was developed. Quinine concentration ranged from 20 to 200 µg/ml. The assay was validated with the accuracy profile method and tested on five different assemblies (device+extension sets) with different dead-space volumes (1.28-2.80 ml) and at two different quinine concentrations (0.3 and 8.0 mg/ml). Rinsing was performed stepwise with water for injection until reaching an undetectable quinine concentration. After fitting the data with a Weibull model, assemblies were compared with an ANOVA performed on ranks (GraphPad, La Jolla, USA). Results The within-day and between-day precision ranges were 0.39-0.81 and 0.48-0.84%, respectively. The lower limit of quantification was 4.26 µg/ml. The volume required to completely rinse the infusion line was different according to the initial drug concentration and to the device assessed: from 6 to 10 ml for a low quinine concentration and from 7 to 17 ml for a high quinine concentration. Conclusion This study shows that a simple, cheap and easy-to-use methodology may be used to assess the rinsing volume of syringe extension sets. The rinsing volume is different according to the tested device.


Policies of dental journals for reporting and monitoring authorship and contributorship.
Authorship contribution is an important issue that has been discussed frequently in the medical literature. There are many reported cases of 'guest' authors (who sign as authors without meeting authorship criteria) and 'ghost' authors (who are credited to get authorship, but for some reason do not sign the article). Therefore, clear and transparent policies for reporting authorship/contributorship are needed in scientific journals. The objective of this survey was to assess the authorship and contributorship policies that are made publically available on the homepages of dental journals. The policies of 64 impact factor-ranked dental journals were assessed with a 6-item checklist based on the International Committee of Medical Journal Editors (ICMJE) guidelines for authorship/contributorship. Most dental journals partially reported the ICMJE guidelines, and therefore the improvement of this reporting is a requirement to promote transparency and integrity in dental research. Moreover, dental journals should develop strategies to improve author adherence to available guidelines for authorship and contributorship.


A first prospective study of the individual straight line velocity of the spermatozoon and its influences on the fertilization rate after intracytoplasmic sperm injection.
The straight line velocity of 500 individual spermatozoa was measured immediately before their direct injection into the cytoplasm of 500 metaphase II oocytes. The straight line velocity (VSL) did not have a normal distribution (P < 0.01) and ranged between 0 and 35 microm/s. The fertilization rate (84%) was significantly (P < 0.008) higher in the quartile of the sperm population with the highest VSL compared to the fertilization rate (68%) in the quartile with the lowest VSL. Embryo cleavage and embryo quality were not different in the quartiles of the sperm population used for injection.


Comparative transcriptomic analysis of Clostridium acetobutylicum biofilm and planktonic cells.
Biofilm-based immobilization of solventogenic Clostridia has been extensively exploited to overcome traditional bottlenecks in biobutanol production like solvent toxicity and low productivities. However, the molecular basis of solventogenic Clostridia biofilm is rarely explored. Here, for the first time, we report DNA array-based study of Clostridium acetobutylicum biofilm cells to elucidate the transcriptional modulation. Results showed that 16.2% of the C. acetobutylicum genome genes within the biofilm cells were differentially expressed, with most genes being up-regulated. The most dramatic changes occurred with amino acid biosynthesis, with sulfur uptake and cysteine biosynthesis being the most up-regulated and histidine biosynthesis being the most down-regulated in the biofilm cells. It was demonstrated that C. acetobutylicum biofilm cells increased metabolic activities probably by up-regulating iron and sulfur uptake and Fe-S cluster biosynthesis genes as well as glycolysis genes. Furthermore, genes involved in sporulation, granulose formation, extracellular polymer degradation, pentose catabolisms, and various other processes were also notably regulated, indicating that the biofilm mode of growth rendered the cells a distinct phenotype. This study provides valuable insights into the transcriptional regulation in C. acetobutylicum biofilm cells and should be highly useful for understanding and developing the biofilm-based processes.


Effects of calcium phosphate solutions on dentin permeability.
Calcium phosphate solutions at various concentrations and pH levels were used to obstruct the dentinal tubules. The effects were evaluated by measurements of permeability through dentin discs and by scanning electron microscopy. Precipitation kinetics were followed by pH changes in the solutions and products were determined by X-ray powder diffraction. The solutions were applied in two ways: (a) calcium and phosphate solutions were mixed before application and (b) one solution (calcium or phosphate) was applied first followed by the other solution. Three kinds of human dentin discs were used; one with smear layer and the other two with tubules exposed by sonication or etched by acid. The high concentration calcium phosphate solutions at pH = 9.5 rapidly precipitated amorphous calcium phosphates that obstructed the dentinal tubules and decreased dentin permeability by 85% or more. At pH = 5.6, the calcium phosphate solutions precipitated large crystals of dicalcium phosphate dihydrate. In this case, the effectiveness in obstructing dentinal tubules was found to be procedure sensitive.


Optimizing epilepsy surgery with intraoperative MR imaging.
The surgical treatment of medically intractable temporal lobe epilepsy includes the resection of temporal lobe structures. Although the reported seizure-free outcomes are highly variable, there is growing evidence that the extent of resection of the mesiotemporal lobe directly correlates with seizure control. A moveable, high-field intraoperative magnetic resonance (MR) system was used to monitor and optimize the resection of the amygdala and hippocampus in 14 epilepsy patients. Fourteen patients with intractable seizures of temporal lobe origin underwent standard preoperative investigations including MR imaging, EEG telemetry, single-photon emission computed tomography, and neuropsychologic and sodium amytal testing. Anterior temporal lobectomy was performed on 10 patients, whereas four were treated with selective amygdalohippocampectomy. Intraoperative electrocorticography was applied as required. For all procedures, the objective was to resect the amygdala completely, and hippocampus to the posterior margin of the brainstem. Interdissection intraoperative MR imaging taken when optimal resection was thought to have been achieved revealed residual unresected amygdala or hippocampus in seven of 14 patients. An unexpected acute hematoma was found in one patient. At 17 months' follow-up, 13 (93%) of 14 patients are seizure free or have significantly improved seizure control. The mobile high-field intraoperative MR system provides high-resolution images without restriction on surgical instruments or techniques. The ability to identify and resect residual mesial temporal lobe targets before craniotomy closure is of potentially tremendous value in optimizing seizure control.


Graphene-Wrapped Anatase TiO2 Nanofibers as High-Rate and Long-Cycle-Life Anode Material for Sodium Ion Batteries.
Anatase TiO2 has been suggested as a potential sodium anode material, but the low electrical conductivity of TiO2 often limits the rate capability, resulting in poor electrochemical properties. To address this limitation, we propose graphene-wrapped anatase TiO2 nanofibers (rGO@TiO2 NFs) through an effective wrapping of reduced graphene oxide (rGO) sheets on electrospun TiO2 NFs. To provide strong electrostatic interaction between the graphene oxide (GO) sheets and the TiO2 NFs, poly(allylamine hydrochloride) (PAH) was used to induce a positively charged TiO2 surface by the immobilization of the -NH3(+) group and to promote bonding with the negatively charged carboxylic acid (-COO(-)) and hydroxyl (-O(-)) groups on the GO. A sodium anode electrode using rGO@TiO2 NFs exhibited a significantly improved initial capacity of 217 mAh g(-1), high capacity retention (85% after 200 cycles at 0.2C), and a high average Coulombic efficiency (99.7% from the second cycle to the 200th cycle), even at a 5C rate, compared to those of pristine TiO2 NFs. The improved electrochemical performances stem from highly conductive properties of the reduced GO which is effectively anchored to the TiO2 NFs.


Intravitreal bevacizumab injections combined with laser photocoagulation for adult-onset Coats' disease.
To evaluate the efficacy of intravitreal bevacizumab injections combined with laser photocoagulation in the treatment of adult-onset Coats' disease. Thirteen eyes of 13 patients suffering from adult-onset Coats' disease were retrospectively included and analyzed. All patients were treated at baseline using intravitreal bevacizumab injections combined with laser photocoagulation. Follow-up treatment was performed as necessary. The mean age of the subjects was 40.3 years, and the mean follow-up period was 24.8 months. The mean number of bevacizumab injections was 2.69, and the mean number of laser treatment sessions was 1.68. The mean baseline best-corrected visual acuity (BCVA) was 0.72 logarithm of the minimum angle of resolution (logMAR; 20/104 Snellen equivalent), while the mean BCVA at the final visit was 0.68 logMAR (20/95; P = 0.548). In three patients (23.0 %), BCVA had improved by more than 3 lines, and seven patients (54.0 %) showed stable BCVA (changes within 2 lines of visual acuity) after treatment. The mean central foveal thickness improved significantly, from 473 μm at baseline to 288 μm at the final visit (P = 0.023). Final BCVA was significantly correlated with a baseline BCVA (P < 0.001; ρ = 0.882). The final BCVA of patients who had subfoveal hard exudates at baseline was significantly worse than that of patients without such exudates (P = 0.005). Intravitreal bevacizumab injection combined with laser photocoagulation may be an effective treatment option for adult-onset Coats' disease. Both poor initial BCVA and the occurrence of subfoveal hard exudates at baseline were associated with poor prognosis and poor therapeutic response.


Hybrid benzofuran-bisindole derivatives: new prototypes with promising anti-hyperlipidemic activities.
A series of different benzofuran-bisindole hybrids were synthesized and evaluated in vitro for their antioxidant and in vivo for antidyslipidemic activity in triton WR-1339 induced hyperlipidemic rats. Among the series, compounds 4a, 4c, 4h and 4j showed significant decrease in plasma levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG) followed by increase in post heparin lipolytic activity (PHLA). In addition, the active hybrids possessed moderate antioxidant properties and increased the plasma lecithin cholesterol acyltransferase (LCAT) activity, which plays a key role in lipoprotein metabolism contributing to an increased level of HDL-C in serum. These results indicate that these hybrids constitute novel prototypes for the management of dyslipidemia.


Age and obesity-associated changes in the expression and activation of components of the AMPK signaling pathway in human right atrial tissue.
Obesity is associated with an increased incidence of left ventricular hypertrophy, diastolic dysfunction, heart failure, and premature cardiac aging. In the heart, intrinsic activation of the AMP-dependent protein kinase (AMPK) plays a pivotal role in the stress response to ischemia and hypertrophy. Furthermore, AMPK is an important regulator of cardiac mitochondrial biogenesis. The purpose of the present study was to investigate the influence of obesity and aging on the AMPK signaling pathway in human cardiac tissue. 60 male cardiac surgery patients were included in the study and divided into 4 groups (old normal weight: ON; old obese: OO; young normal weight: YN, young obese: YO) according to their body mass index (18.5-25: normal weight or 30-35: obese) and age (<55 years: young or >70: old) with 15 patients each. Right atrial tissue (RA) was analyzed for the expression of the AMPK upstream kinases CAMKK and LKB1, activation of AMPK as well as phosphorylation of the AMPK downstream targets ACC, eEF2, mTOR and eNOS. Epicardial adipose tissue was analyzed for the expression of the endogenous AMPK activator adiponectin. The metabolic state of all patients was further characterized in fasting blood samples. Old patients (ON, OO) and young obese (YO) subjects displayed higher fasting glucose, insulin and leptin serum levels compared to the young, normal weight group, although HbA1c was below the threshold required for the diagnosis of type 2 diabetes. Serum adiponectin as well as total adiponectin protein expression in epicardial adipose tissue was decreased in these three groups. Analyses of adiponectin isoforms by native gel electrophoresis revealed significant differences in the high molecular weight (HMW) isoforms between the groups. Despite the low total serum adiponectin and HMW adiponectin, AMPK activation was high in the RA of obese patients (YO, OO). Among the AMPK upstream kinases, LKB1 expression showed a strong positive correlation with AMPK activation. While the phosphorylation of the AMPK downstream targets mTOR, eEF-2 and ACC was not altered, phospho-eNOS was significantly lower in old patients (ON, OO). Despite strong AMPK activation, mitochondrial biogenesis and respiration were impaired in old (ON, OO) and young obese (YO) subjects. These data indicate that obesity and aging result in significant changes although many direct parameters in the AMPK signaling pathway are not changed in the same direction. LKB1 may represent a stronger activator of the AMPK pathway than adiponectin or the CAMKKs in human right atrial tissue.


N-terminal Gag domain required for foamy virus particle assembly and export.
Among the Retroviridae, foamy viruses (FVs) exhibit an unusual way of particle assembly and a highly specific incorporation of envelope protein into progeny virions. We have analyzed deletions and point mutants of the prototypic FV gag gene for capsid assembly and egress, envelope protein incorporation, infectivity, and ultrastructure. Deletions introduced at the 3' end of gag revealed the first 297 amino acids (aa) to be sufficient for specific Env incorporation and export of particulate material. Deletions introduced at the 5' end showed the region between aa 6 and 200 to be dispensable for virus capsid assembly but required for the incorporation of Env and particle egress. Point mutations were introduced in the 5' region of gag to target residues conserved among FVs from different species. Alanine substitutions of residues in a region between aa 40 and 60 resulted in severe alterations in particle morphology. Furthermore, at position 50, this region harbors the conserved arginine that is presumably at the center of a signal sequence directing FV Gag proteins to a cytoplasmic assembly site.


Correction of the disease phenotype in the mouse model of Stargardt disease by lentiviral gene therapy.
Autosomal recessive Stargardt disease (STGD1) is a macular dystrophy caused by mutations in the ABCA4 (ABCR) gene. The disease phenotype that is most recognized in STGD1 patients, and also in the Abca4-/- mouse (a disease model), is lipofuscin accumulation in retinal pigment epithelium. Here, we tested whether delivery of the normal (wt) human ABCA4 gene to the subretinal space of the Abca4 -/- mice via lentiviral vectors would correct the disease phenotype; that is, reduce accumulation of the lipofuscin pigment A2E. Equine infectious anemia virus (EIAV)-derived lentiviral vectors were constructed expressing either the human ABCA4 gene or the LacZ reporter gene under the control of the constitutive (CMV) or photoreceptor-specific (Rho) promoters. Abca4-/- mice were injected subretinally with 1 microl ( approximately 5.0 x 10(5) TU) of each EIAV vector in one eye at postnatal days 4 and 5. An injection of saline, an EIAV-null vector, or an uninjected contralateral eye served as a control. Mice were killed at various times after injection to determine photoreceptor (PR) transduction efficiency and A2E concentrations. EIAV-LacZ vectors transduced from 5 to 20% of the PRs in the injected area in mice. Most importantly, a single subretinal injection of EIAV-CMV-ABCA4 to Abca4-/- mouse eyes substantially reduced disease-associated A2E accumulation compared to untreated and mock-treated control eyes. Treated eyes of Abca4-/- mice accumulated 8-12 pmol per eye (s.d.=2.7) of A2E 1 year after treatment, amounts comparable to wt controls, whereas mock-treated or untreated eyes had 3-5 times more A2E (27-39 pmol per eye, s.d.=1.5; P=0.001-0.005). Although extrapolation to humans requires caution, the high transduction efficiency of both rod and cone photoreceptors and the statistically significant reduction of A2E accumulation in the mouse model of STGD1 suggest that lentiviral gene therapy is a potentially efficient tool for treating ABCA4-associated diseases.


The ocular secretory immune system of the rat.
Ocular tissues and tears of adult male rats were examined for the presence of immunoglobulins (Ig) and secretory component (SC). By immunofluorescent analysis, we found the highest density of Ig-containing cells in the exorbital (lacrimal) gland. In contrast, few if any Ig-containing cells were observed in the conjunctiva or Harder's gland. IgA was the most frequent cell-associated isotype identified in the exorbital gland, and the number of IgA-containing cells was much greater than that of IgM- or IgG-containing cells. With respect to IgG, cell counts were fairly evenly distributed among the various subclasses. No IgE-containing cells were detected in ocular tissues. SC was identified exclusively within the acinar cells of the exorbital gland. In tears, IgA was the predominant isotype and occurred almost entirely in the polymeric form. Of the IgG subclasses, IgG 2a was present in the greatest concentration. Only trace amounts of IgG 2b were found, and IgG 1, IgG 2c and IgM could not be detected. The level of free SC in tears was relatively high, compared to the concentration of free SC reported in other mucosal secretions. These results suggest that the exorbital gland is the primary tissue associated with the ocular secretory immune system of the rat. Furthermore, our findings indicate that rat tears contain components that may provide immune defense for the ocular surface.


Effect of pterygium on contrast sensitivity.
The purpose of this study is to evaluate the effect of pterygium on contrast sensitivity. Thirty-six eyes with pterygium and 18 eyes without pterygium were included in the study. The size of the pterygium was measured on the slit lamp both vertically at the limbus and categorized into three groups (≤3, 3.1 to ≤5, >5 mm), and horizontally on the cornea and categorized into two groups (0.5 to ≤2, >2 mm), and the area calculated by multiplying the two measurements was then categorized into three groups (≤7, 7.1 to ≤14, >14 mm(2)). Contrast sensitivity was measured using CSV-1000E charts (Vector Vision) at 3, 6, 12 and 18 cycles per degree under photopic and mesopic conditions. The mean vertical length of pterygium was 4.41 ± 1.12 mm, mean horizontal width was 2.09 ± 0.68 mm and mean area was 9.7 ± 5.01 mm(2). Significant differences in both photopic and mesopic contrast sensitivities at all frequencies were noted between normal eyes and vertical length of pterygium >3 mm, horizontal width ≥0.5 mm and area >7 mm(2). Contrast sensitivity had significant negative correlation with all three parameters. Pterygium with vertical length >3 mm, horizontal width ≥0.5 mm and area >7 mm(2) caused a significant decrease in both photopic and mesopic contrast sensitivity at all spatial frequencies. Contrast sensitivity had significant negative correlation with all three parameters.


Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis.
Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD2, is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD2 and its metabolite, but not PGE2 and a panel of cytokines including TGF-β, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD2-dependent, rather than PGE2-dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD2, as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS.


Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety).
The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.


Antifungal activity of some Tanzanian plants used traditionally for the treatment of fungal infections.
Using the ethnobotanical approach, some Tanzanian plants reported to be used by traditional healers for the treatment of oral candidiasis and fungal infections of the skin were collected and screened for their antifungal activity against Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida krusei and Cryptococcus neoformans. A total of 65 crude methanol extracts belonging to 56 plant species and 38 families were screened using the broth microdilution method, according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI) (formerly, National Committee for Clinical and Laboratory Standards) [National Committee for Clinical Laboratory Standards, 2002. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. Approved Standard-2nd Edition M27-A2, National Committee for Clinical Laboratory Standards, Wayne, PA, USA]. Among the tested plant species, 45% (25 species) showed antifungal activity against one or more of the test fungi. The most susceptible yeasts were Cryptococcus neoformans, followed by Candida krusei, Candida tropicalis, and Candida parapsilosis. The least susceptible were Candida albicans and Candida glabrata. Strong antifungal activity was exhibited by extracts of Clausena anisata Oliv., Sclerocariya birrea Sond, Turraea holstii Gurk, Sterculia africana (Lour) Fiori, Acacia robusta subsp. Usambarensis (Taub) Brenan, Cyphosterma hildebrandti (Gilg), Desc, Elaeodendron buchannanii (Lows), Acacia nilotica (L.) Wild ex Del, Jatropha multifida L., and Pteridium aquilinum (L.) Kuhn.


Isolation of Environmental Bacteria Able to Degrade Sterols and/or Bile Acids: Determination of Cholesterol Oxidase and Several Hydroxysteroid Dehydrogenase Activities in Rhodococcus, Gordonia, and Pseudomonas putida.
Interest about the isolation and characterization of steroid-catabolizing bacteria has increased over time due to the massive release of these recalcitrant compounds and their deleterious effects or their biotransformation derivatives as endocrine disruptors for wildlife, as well as their potential use in biotechnological approaches for the synthesis of pharmacological compounds. Thus, in this chapter, an isolation protocol to select environmental bacteria able to degrade sterols, bile acids, and androgens is shown. Moreover, procedures for the determination of cholesterol oxidase or different hydroxysteroid dehydrogenase activities in Pseudomonas putida DOC21, Rhodococcus sp. HE24.12, Gordonia sp. HE24.4J and Gordonia sp. HE24.3 are also detailed.


Morphological and biochemical analyses of original and regenerated lizard tails reveal variation in protein and lipid composition.
Caudal autotomy, or voluntary self-amputation of the tail, is a common and effective predator evasion mechanism used by most lizard species. The tail contributes to a multitude of biological functions such as locomotion, energetics, and social interactions, and thus there are often costs associated with autotomy. Notably, relatively little is known regarding bioenergetic costs of caudal autotomy in lizards, though key morphological differences exist between the original and regenerated tail that could alter the biochemistry and energetics. Therefore, we investigated lizard caudal biochemical content before and after regeneration in three gecko and one skink species. Specifically, we integrated biochemical and morphological analyses to quantify protein and lipid content in original and regenerated tails. All lizards lost significant body mass, mostly protein, due to autotomy and biochemical results indicated that original tails of all species contained a greater proportion of protein than lipid. Morphological analyses of two gecko species revealed interspecific differences in protein and lipid content of regenerated lizard tails. Results of this study contribute to our understanding of the biochemical consequences of a widespread predator evasion mechanism.


Reproductive health of Asian women: a comparative study with hospital and community perspectives.
A comparative study of Asian and non-Asian women's reproductive health was performed. The hospital case notes of 48 Asian and 51 non-Asian women, matched for age, were examined. Asian women had shorter stature, bigger families, booked later for antenatal care, and were less likely to have a cervical smear taken. Of the above, 30 Asian and 24 non-Asian women were interviewed in their homes. Many Asian women had difficulties with the English language and a low literacy rate which gave rise to communication barriers during health care. Their knowledge of procedures and tests such as amniocentesis, self examination of the breast etc. was comparatively low. Fewer Asians attended parent-craft classes or did post-natal exercises. Many disliked, and some refused, vaginal examination by male doctors. Despite equal access, Asian women were less well informed and made lesser use of services. Lack of knowledge and difficulties of communication, rather than negative attitudes, may explain Asian women's lesser use of services and to some extent the poor outcome of pregnancy observed in many studies.


Protein kinase C stimulatory activity in the pseudopregnant rat ovary.
Ovarian cytosol from pseudopregnant rats was heated to 80-90 degrees C for 2 min and precipitated proteins removed by centrifugation. The supernatant of the heated ovarian cytosol contained no protein kinase C activity but when added to a control preparation containing protein kinase C, enzyme activity was increased to 200% of control. The stimulatory activity was stable to heating for 10 min, was retained on a centrifugal filtration device with a 100,000 M(r) cut-off, did not affect cAMP-dependent protein kinase, was not extractable in petroleum ether or chloroform/methanol (2:1), and enhanced the phosphorylation of protein kinase C-specific peptide substrates. The stimulatory factor was calcium-dependent and could substitute for phosphatidylserine and diacylglycerol in the protein kinase C assay. This stimulatory factor may provide a mechanism whereby the response of protein kinase C to hormonal activation could be regulated by the cell.


Developmental genetic malformations of the cerebral cortex.
Cortical malformations give rise to severe clinical manifestations such as epilepsy and mental retardation, but sometimes to more subtle problems like dyslexia. From a clinical standpoint, such structural abnormalities are diagnosed by radiographic and histologic findings, with disease classifications often based on these observations. Using this categorization, many of the responsible genes have been determined and now provide a means of understanding the molecular basis of the neurologic disorders. This review discusses the known genetic developmental syndromes in the context of the observed cortical malformations, the expression and function of the responsible genes, and their potential roles during the various stages of central nervous system development.


Influence of a pulp and paper mill effluent on aspects of distribution, survival and feeding of Nipigon Bay, Lake Superior, larval fish.
Surface distribution of Nipigon Bay larval fish was characterized by high abundance, between 500 and 2100 larval fish/10,000 m3 near shore, particularly in proximity to the pulp and paper mill effluent discharge, and low abundance, less than 100/10,000 m3 away from shore. Static bioassay indicated that approximately 60% effluent concentration was intolerable to the natural mixed larval fish community. No wood fibre was found among stomach contents and no difference was apparent in stomach contents of fish caught in influenced and uninfluenced areas. Data therefore suggest that larval fish either were not greatly influenced by plume conditions or were transients.


Human adaptation to diverse biomes over the past 3 million years.
To investigate the role of vegetation and ecosystem diversity on hominin adaptation and migration, we identify past human habitat preferences over time using a transient 3-million-year earth system-biome model simulation and an extensive hominin fossil and archaeological database. Our analysis shows that early African hominins predominantly lived in open environments such as grassland and dry shrubland. Migrating into Eurasia, hominins adapted to a broader range of biomes over time. By linking the location and age of hominin sites with corresponding simulated regional biomes, we also find that our ancestors actively selected for spatially diverse environments. The quantitative results lead to a new diversity hypothesis: Homo species, in particular Homo sapiens, were specially equipped to adapt to landscape mosaics.


An Urgent Need for a Common Framework for the Articulation, Design and Reporting of Surgical System Strengthening Interventions Comment on "Improving Access to Surgery Through Surgical Team Mentoring - Policy Lessons From Group Model Building With Local Stakeholders in Malawi".
Nearly 60% of the world's inhabitants lack access to timely, safe, and ffordable emergency and essential surgical, anesthetic, and obstetric (SAO) services when needed. Although acknowledged as an important step in resolving this disparity, situation analysis informed development of national surgical, obstetric and anesthesia plans (NSOAPs) has not been performed widely. There are even fewer published examples of NSOAP driven SAO system vulnerability resolving policy interventions, potentially hindering broader acceptance and drafting. Thus, there is urgent need for alignment of academic global surgery activities through a common framework for SAO strengthening intervention articulation, design and reporting which can be informed by the Malawian experience and others. This is a logical next step in the evolution of surgical system science as we move towards the articulation of actionable inequity resolving interventions through stakeholder engagement embedded in a plan-do-study-act (PDSA) model for iterative refinement of strengthening policies.


Haploinsufficiency of cathepsin D leads to lysosomal dysfunction and promotes cell-to-cell transmission of α-synuclein aggregates.
Lysosomal dysfunction has been implicated both pathologically and genetically in neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease (PD). Lysosomal gene deficiencies cause lysosomal storage disorders, many of which involve neurodegeneration. Heterozygous mutations of some of these genes, such as GBA1, are associated with PD. CTSD is the gene encoding Cathepsin D (CTSD), a lysosomal protein hydrolase, and homozygous CTSD deficiency results in neuronal ceroid-lipofuscinosis, which is characterized by the early onset, progressive neurodegeneration. CTSD deficiency was also associated with deposition of α-synuclein aggregates, the hallmark of PD. However, whether partial deficiency of CTSD has a role in the late onset progressive neurodegenerative disorders, including PD, remains unknown. Here, we generated cell lines harboring heterozygous nonsense mutations in CTSD with genomic editing using the zinc finger nucleases. Heterozygous mutation in CTSD resulted in partial loss of CTSD activity, leading to reduced lysosomal activity. The CTSD mutation also resulted in increased accumulation of intracellular α-synuclein aggregates and the secretion of the aggregates. When α-synuclein was introduced in the media, internalized α-synuclein aggregates accumulated at higher levels in CTSD+/- cells than in the wild-type cells. Consistent with these results, transcellular transmission of α-synuclein aggregates was increased in CTSD+/- cells. The increased transmission of α-synuclein aggregates sustained during the successive passages of CTSD+/- cells. These results suggest that partial loss of CTSD activity is sufficient to cause a reduction in lysosomal function, which in turn leads to α-synuclein aggregation and propagation of the aggregates.


Therapeutic drug monitoring of amikacin in preterm and term neonates with late-onset sepsis. Can saliva samples replace plasma samples?
Amikacin is an aminoglycoside antibiotic that is frequently used for the treatment of neonatal late-onset sepsis, for which therapeutic drug monitoring (TDM) is advised. In order to decrease the TDM associated burden of plasma sampling, a noninvasive TDM method using saliva samples was investigated. This was a prospective single-centre, observational feasibility study with 23 premature and term neonates from whom up to 8 saliva samples were collected, together with residual plasma from clinical routine. Amikacin concentrations in saliva and plasma were quantified with liquid chromatography-tandem mass spectrometry. A population pharmacokinetic analysis was performed to develop an integrated pharmacokinetic model of amikacin in plasma and saliva and for the identification of covariates. TDM performance of different sampling regimens was evaluated using Monte Carlo simulations in a fictional cohort of representative neonates (n = 10 000). Amikacin could be detected in saliva and a saliva compartment was appended to a 2-compartment plasma model. First-order absorption (k13 ) of the saliva compartment was 0.0345 h-1 with an interindividual variability of 45.3%. The rate of first-order elimination (k30 ) was 0.176 h-1 . Postmenstrual age had a significant negative covariate effect on k13 , with an exponent of -4.3. Target attainment increased from 77.6 to 79.2% and from 79.9 to 83.2% using 1-to 5 saliva samples or 1-5 plasma samples, respectively. TDM of amikacin using saliva samples results in target attainment comparable to plasma samples and may be beneficial for (premature) neonates with late-onset sepsis.


Association between first language and SARS-CoV-2 infection rates, hospitalization, intensive care admissions and death in Finland: a population-based observational cohort study.
Motivated by reports of increased risk of coronavirus disease 2019 (COVID-19) in ethnic minorities of high-income countries, we explored whether patients with a foreign first language are at an increased risk of COVID-19 infections, more serious presentations, or worse outcomes. In a retrospective observational population-based quality registry study covering a population of 1.7 million, we studied the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), admissions to specialist healthcare and the intensive care unit (ICU), and all-cause case fatality in different language groups between 27th February and 3rd August 2020 in Southern Finland. A first language other than Finnish, Swedish or Sámi served as a surrogate marker for a foreign ethnic background. In total, 124 240 individuals were tested, and among the 118 300 (95%) whose first language could be determined, 4005 (3.4%) were COVID-19-positive, 623 (0.5%) were admitted to specialized hospitals, and 147 (0.1%) were admitted to the ICU; 254 (0.2%) died. Those with a foreign first language had lower testing rates (348, 95%CI 340-355 versus 758, 95%CI 753-762 per 10 000, p < 0.0001), higher incidence (36, 95%CI 33-38 versus 22, 95%CI 21-23 per 10 000, p < 0.0001), and higher positivity rates (103, 95%CI 96-109 versus 29, 95%CI 28-30 per 1000, p < 0.0001). There was no significant difference in ICU admissions, disease severity at ICU admission, or ICU outcomes. Case fatality by 90 days was 7.7% in domestic cases and 1.2% in those with a foreign first language, explained by demographics (age- and sex-adjusted HR 0.49, 95%CI 0.21-1.15). The population with a foreign first language was at an increased risk for testing positive for SARS-CoV-2, but when hospitalized they had outcomes similar to those in the native, domestic language population. This suggests that special attention should be paid to the prevention and control of infectious diseases among language minorities.


[Promoting autonomy by redesigning support in psychiatry].
Therapeutic patient education in psychiatry is a unique form of support in which the relational aspect is used as a means of developing the patient's capabilities and awareness of the disorder. This time helps to support users' autonomy and favours health professionals' participative approach.


The pharmacokinetics of clarithromycin and its 14-OH metabolite.
Clarithromycin has been administered to 486 subjects in 23 different Phase I studies. Absorption of clarithromycin is rapid and peak concentrations are reached within 2 h of oral dosing. Bioavailability of clarithromycin is c. 50% after oral dosing. However, additional clarithromycin is absorbed and converted into 14-OH-clarithromycin in the liver before entering the systemic circulation. The antimicrobial activity of 14-OH-(R)-clarithromycin, if anything, is superior to that of the parent compound, so that the total absorption of biologically active substance is more than 50% of the administered dose. Peak serum concentrations after oral administration of a 250 mg, film-coated tablet of clarithromycin are 1.5 mg l-1 clarithromycin and 0.8 mg l-1 of 14-OH-(R)-clarithromycin. Clarithromycin is 72% bound to plasma proteins at a concentration of 0.45 mg l-1 but binding decreases with increasing concentration of clarithromycin. Concentrations of clarithromycin in lung are approximately five-fold greater than serum concentrations. Clarithromycin is metabolized in the liver and in the stomach. Approximately 22% of an oral dose is recovered as parent compound, 18% in the urine and 4% in the faeces. Clearance of clarithromycin decreases with increasing dose, probably because of saturable hepatic metabolism. There is a progressive increase in serum concentrations of clarithromycin and 14-OH-(R)-clarithromycin with renal impairment so that doses may need to be reduced in severe impairment (glomerular filtration rate less than 30 ml min-1). No effect of age on clarithromycin clearance has been demonstrated when clarithromycin clearance is corrected for creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)


Lymph nodes primary staging of colorectal cancer in 18F-FDG PET/MRI: a systematic review and meta-analysis.
To assess the diagnostic efficacy of 18F-FDG PET/MRI for lymph node (LN) metastasis primary staging in patients with colorectal cancer (CRC). This study was conducted and reported in accordance with the PRISMA-DTA statement. Electronic databases (PubMed, Embase, Cochrane Library) were searched for studies on 18F-FDG PET/MRI for diagnosing LN metastasis. The pooled sensitivity (SEN), specificity (SPE), and area under the curve (AUC) were applied to assess the diagnostic performance. Heterogeneity was identified and processed using meta-regression and sensitivity analysis. All data analyses were performed via STATA 15 and Meta-Disc 1.4 software. There were finally 7 studies included, involving a total of 184 patients. The Spearman rank correlation coefficient was 0.108 (P = 0.818), with no threshold-effect observed. The pooled SEN was 0.81 (95%CI 0.66-0.90) and the SPE was 0.89 (95% CI 0.73-0.96). In sub-groups, prospective groups demonstrated to have the highest SEN of 0.92 (95%CI 0.79-1.00). The studies conducted by Catalano et al. and Kang et al. were considered to be potential sources of heterogeneity. 18F-FDG PET/MRI has shown remarkable diagnostic performance in identification of LN metastases in newly diagnosed CRC patients. It would be of great application value for the primary staging of CRC lymph node metastases.


Are conventional pressure-flow measurements dependent upon filled volume?
To determine, in a prospective study, whether detrusor pressure (p(det.Qmax)) and maximum urinary flow rate (Q(max)) measurements obtained after filling to maximum cystometric capacity (MCC) differ from those obtained with filling restricted to average voided volume (V(void)), as standard protocols for pressure flow studies (PFS) mandate bladder filling until the subject has a strong desire to void, which aids standardization but further divorces the test from real-life experience. After calculating the appropriate sample size, 84 patients attending for PFS with an adequately completed 3-day frequency-volume chart were recruited. Each underwent two consecutive PFS with filling to MCC and average V(void) in a random order, and measurements of p(det.Qmax) and Q(max) were compared. For men, the agreement for a diagnosis of obstruction between the tests was also assessed. Complete data were obtained from 76 (90%) of the patients, with a mean (range) age of 64 (20-94) years. The mean (sd) difference between MCC and average V(void) was 134 (113) mL (P < 0.01). There were no significant differences between estimates of Q(max), at - 0.1 (3) mL/s (P = 0.75), and of p(det.Qmax), at - 1 (13) cmH(2)O (P = 0.91), obtained within each patient. For men there was 91% agreement (32 of 35) in the classification of obstruction. Restriction of filling to the average V(void) during PFS allows a closer approximation to normal voiding and results in no clinically relevant change to the value of standard pressure-flow measurements or alters individual classification of obstruction.


Ryegrass cv. Lema and guava cv. Paluma biomonitoring suitability for estimating nutritional contamination risks under seasonal climate in Southeastern Brazil.
The risks posed by nutrient deposition due to air pollution on ecosystems and their respective services to human beings can be appropriately estimated by bioindicator plants when they are well acclimated to the study region environmental conditions. This assumption encouraged us to comparatively evaluate the accumulation potential of ryegrass cv. Lema and guava cv. Paluma macro and micronutrients. We also indicated the most appropriate species for biomonitoring nutrient contamination risks in tropical areas of Southeastern Brazil, which are characterized by marked dry and wet seasons and complex mixtures of air pollutants from different sources (industries, vehicle traffic and agriculture). The study was conducted in 14 sites with different neighboring land uses, within the Metropolitan Region of Campinas, central-eastern region of São Paulo State. The exposure experiments with ryegrass and guava were consecutively repeated 40 (28 days each) and 12 (84 days each) times, respectively, from Oct/2010 to Sept/2013. Macro and micronutrients were analyzed and background concentrations and enrichment ratios (ER) were estimated to classify the contamination risk within the study region. Significantly higher ER suggested that ryegrass were the most appropriate accumulator species for N, S, Mg, Fe, Mn, Cu and Zn deposition and guava for K, Ca, P and B deposition. Based on these biomonitoring adjustments, we concluded that the nutrient deposition was spatially homogeneous in the study area, but clear seasonality in the contamination risk by nutritional inputs was evidenced. Significantly higher contamination risk by S, Fe, K and B occurred during the dry season and enhanced contamination risk by Mn, Cu and Zn were highlighted during the wet season. Distinctly high contamination risk was estimated for S, Fe and Mn in several exposure experiments.


Paragonimus westermani in Malaysian Felidae and Viverridae: probable modes of transmission in relation to host feeding habits.
Examination of naturally infected felids and viverrids in Malaysia confirmed previously published records which indicated that P. westermani occurred only in felid cats. Felis planiceps and F. temnickli were reported as new host records. Analysis of stomach contents revealed no crab remains in either family of cats, but confirmed that felids were strictly carnivorous while viverrids were often omnivorous. In feeding experiments, only viverrids ate the host crabs Potomiscus johorensis and Parathelphusa maculata. The probable transmission of P. westermani to felids via paratenic hosts was discussed.


Risk factors for ipsilateral adrenal involvement in renal cell carcinoma.
We retrospectively review patients treated for renal cell carcinoma at 19 institutes in collaboration with the Japanese Society of Renal Cancer, to clarify the risk factors for ipsilateral adrenal involvement (IADI). The clinicopathologic factors of the 30 patients with IADI were compared with those of the 926 control patients without IADI, and independent predictors for IADI were identified by multivariate analysis. Preoperative computed tomography (CT) could detect 83.3% of the instances of synchronous ipsilateral adrenal metastasis. Patients with IADI had significantly larger primary tumors, higher pT stages and histologic grades, and higher percentages of upper pole involvement, microvascular invasion, spindle-cell-type tumors, lymph node metastasis (LNM), and distant metastasis (DM) outside the ipsilateral adrenal gland (IAd) than in control patients. Multivariate logistic regression analysis of clinical factors revealed that tumor size greater than 5.5 cm, pT stage of 3 or higher, LNM, and DM outside IAd, but not upper pole involvement, were significant predictors of IADI. Tumor size greater than 5.5 cm, clinical T stage of 3 or higher (tumor for which pT stage of 3 or higher is suspected), LNM, and DM outside IAd seemed to be important preoperative indicators of IADI. These factors and CT findings would be useful preoperative indicators for ipsilateral adrenalectomy. Moreover, patients with renal cell carcinoma who have normal adrenal on CT, have a T1 tumor extending less than 5.5 cm, and have neither LNM nor DM are good candidates for adrenal-sparing nephrectomy.


Variation in the biological characteristics of BAC during ultrasonic regeneration.
Ultrasonic treatment has been shown to have a favorable effect on the regeneration of spent biological activated carbon (BAC) from drinking water treatment plants. In this study, the use of ultrasound as a regeneration method had a significant effect on the recovery of spent BAC after 7.5 years of use; it effectively increased the iodine value from 300 mg/g to 600 mg/g and restored the specific surface area and pore volume of BAC. Ultrasound effectively changed the structure of the biofilm inside and on the surfaces of BAC particles, on the basis of confocal laser scanning microscopy (CLSM) images. The thickness of the surface biofilm attached to BAC reached an "active" level (about 100 μm) at the regeneration frequency of 40 kHz. The dehydrogenase activity significantly improved from 4.50 mg TF/g BAC to 9.13 mg TF/g BAC, and the content of adenosine-triphosphate (ATP) in regenerated BAC was maintained at a high level (2.501 × 10-6g ATP/g BAC), thus allowing the development of microbial growth. The production of soluble microbial products (SMPs) from regenerated BAC decreased during the reuse process. The removal efficiency of DOC, CODMn, NH4+ and NO3- control increased by approximately 78%, 71%, 50% and 20%, respectively.


Three dimensional spatial memory and learning in real and virtual environments.
Human orientation and spatial cognition partly depends on our ability to remember sets of visual landmarks and imagine their relationship to us from a different viewpoint. We normally make large body rotations only about a single axis which is aligned with gravity. However, astronauts who try to recognize environments rotated in 3 dimensions report that their terrestrial ability to imagine the relative orientation of remembered landmarks does not easily generalize. The ability of human subjects to learn to mentally rotate a simple array of six objects around them was studied in 1-G laboratory experiments. Subjects were tested in a cubic chamber (n = 73) and a equivalent virtual environment (n = 24), analogous to the interior of a space station node module. A picture of an object was presented at the center of each wall. Subjects had to memorize the spatial relationships among the six objects and learn to predict the direction to a specific object if their body were in a specified 3D orientation. Percent correct learning curves and response times were measured. Most subjects achieved high accuracy from a given viewpoint within 20 trials, regardless of roll orientation, and learned a second view direction with equal or greater ease. Performance of the subject group that used a head mounted display/head tracker was qualitatively similar to that of the second group tested in a physical node simulator. Body position with respect to gravity had a significant but minor effect on performance of each group, suggesting that results may also apply to weightless situations. A correlation was found between task performance measures and conventional paper-and-pencil tests of field independence and 2&3 dimensional figure rotation ability.


Intestinal absorption of aluminium from antacids: a comparison between hydrotalcite and algeldrate.
The intestinal absorption of aluminium (Al) from the antacid hydrotalcite (Ultacit) was compared with that from algeldrate (Algeldratum des-acidans) in 8 healthy human subjects in a cross-over study. The level of Al in serum (AlS) was increased in 7 out of 8 subjects 7 hr after intake of 6 g algeldrate while AlS did not rise after intake of 8 g hydrotalcite--a dose with at least comparable acid-neutralizing capacity--in any of the subjects.


Evaluation of antiherpetic activity of crude extract and fractions of Avicenna marina, in vitro.
This study was carried out to check antiherpetic substances of crude methanol leaf extract of Avicenna marina and its column chromatographic fractions. Herpes simplex virus 2 (HSV-2) is a harmful pathogen especially in highly susceptible individuals. The antiherpetic activity of crude methanol extract and sub-fractions was performed in different concentrations (20, 2, 0.2, and 0.02μg/ml) by use of plaque-forming unit (PFU) assay and real time polymerase chain reaction (PCR) assay. The most active fraction analyzed by NMR contained luteolin 7-O-methylether 3'-O-beta-d-glucoside (LMEG). The other active fraction was detected by HPLC as luteolin. The apparent effective concentrations for 50% plaque reduction (EC50) of crude methanol extract, LMEG, luteolin and ACV were 10, 5, 16.6 and 2.97μg/ml, respectively. The three extracts showed no cytotoxic effect on Vero cell line at concentrations of 32μg/ml or below. According to the consequences of time-of-addition studies, antiherpetic compound LMEG exerted an inhibitory effect on the early stage of HSV-2 infection during which it was added. In conclusion, LMEG isolated from A. marina could probably inhibit HSV attachment to the cell membrane and its entry into the cell.


Local conformal autoencoder for standardized data coordinates.
We propose a local conformal autoencoder (LOCA) for standardized data coordinates. LOCA is a deep learning-based method for obtaining standardized data coordinates from scientific measurements. Data observations are modeled as samples from an unknown, nonlinear deformation of an underlying Riemannian manifold, which is parametrized by a few normalized, latent variables. We assume a repeated measurement sampling strategy, common in scientific measurements, and present a method for learning an embedding in [Formula: see text] that is isometric to the latent variables of the manifold. The coordinates recovered by our method are invariant to diffeomorphisms of the manifold, making it possible to match between different instrumental observations of the same phenomenon. Our embedding is obtained using LOCA, which is an algorithm that learns to rectify deformations by using a local z-scoring procedure, while preserving relevant geometric information. We demonstrate the isometric embedding properties of LOCA in various model settings and observe that it exhibits promising interpolation and extrapolation capabilities, superior to the current state of the art. Finally, we demonstrate LOCA's efficacy in single-site Wi-Fi localization data and for the reconstruction of three-dimensional curved surfaces from two-dimensional projections.


Determination of 90Sr traces in medical 90Y after separation on DGA column.
A new analytical procedure for (90)Sr determination in freshly milked (90)Y from a (90)Sr/(90)Y generator is described. To a solution containing 125 mg of Sr a 200 to 400 MBq sample of (90)Y is added and strontium is separated from (90)Y using DGA column of 1 mL volume. (90)Sr is recovered in a yield close to 100% and counted in a liquid scintillation spectrometer (LSC). The separated strontium is slightly contaminated with (90)Y in the range from 7 to 19% of (90)Sr activity. The separation and counting can be completed within 30 min. The detection limit in 900 s counting time is equal to about 0.2 Bq. This corresponds to (90)Sr/(90)Y activity ratio of 10(-8) level.


[Neuronavigation-assisted resection of gliomas near eloquent regions].
To evaluate the effect of the neuronavigation system in operation of gliomas near eloquent regions. The brain LAB VV2 navigation system was used in 11 patients with gliomas near eloquent regions. The value of this system for glioma resection was assessed, and the accuracy and notice for application were discussed. The mean registration error was (1.5 +/- 0.7) mm in the patients. Total lesion removal was achieved in 9 patients (81.8%). The clinical status of all patients improved, and their functions of motor were not significantly affected. No complications were attributed to the use of this system. The neuronavigation system is reliable and accurate in surgical treatment of gliomas near eloquent regions. It increases the fraction of radical in glioma resection without injury to the critical functions.


Leiomyoma of the lung. Literature review and case report.
Sixty-five cases of pulmonary leiomyomas previously have been reported. A new case is reported of a 23-year-old man. Electron microscopy showed typical ultrastructural smooth muscle differentiation. In a series of 66 cases from the world literature, the ratio of females to males was of 1.5:1. There is a slight preponderance of parenchymal localization versus bronchial. The average age of presentation was 37 years, and the tumor was found rarely in the aged or in children. The diagnosis of pulmonary leiomyoma should be made with the knowledge of recently-introduced concepts of smooth-muscle proliferation in the lung and the possibility that metastatic low-grade leiomyosarcoma may simulate a primary leiomyoma.


Effect of PPARgamma ligands on the viability of gastric epithelial cells.
[corrected] Peroxisome proliferator-activated receptors (PPAR) are a family of three nuclear receptors (PPARalpha, PPARdelta, and PPARgamma). Although recent evidence suggests a role for PPARgamma in the regulation of colonic epithelial cell growth, the role for PPARgamma in the stomach has not been established. To examine the expression of PPARgamma and the effects of PPARgamma ligands on the viability of gastric epithelial cells. MKN45 cells and primary cultured rat gastric epithelial cells were used. Troglitazone (TGZ) and 15-deoxy-Delta12, 14-prostaglandin J2 (15d-PGJ2) were used as PPARgamma ligands. Expression of PPARgamma was examined by RT-PCR and Western blot analysis. Cell viability was measured by WST-1 assay and TUNEL assay was performed to detect apoptosis. MKN45 cells expressed all subtypes of PPAR. PPARgamma ligands decreased cell viability and induced cell death in a dose-dependent manner, whereas ligands for PPARalpha and PPARdelta had no significant effect. TUNEL assay showed that this cell death is apoptosis. Primary cultured rat gastric epithelial cells also expressed PPARgamma and activation of PPARgamma decreased cell viability. These results suggest that PPARgamma plays an important role in the regulation of cell growth and cell death in gastric epithelial cells.


Humoral response to coronavirus disease-19 vaccines is dependent on dosage and timing of rituximab in patients with rheumatoid arthritis.
Humoral response to vaccines in RA patients treated with rituximab (RTX) in standard dosages (≥1000 mg) is decreased. Ultra-low dosages (500 or 200 mg) may have better response. Also, timing after latest RTX infusion may be an important variable. We aimed to investigate the influence of RTX dosage and timing on response to COVID-19 vaccination in RA patients. A single-centre observational study (n = 196) investigated the humoral response, measured by total Ig anti-COVID-19 assay (positive response ≥1.1), 2-6 weeks after complete COVID-19 vaccination. A multivariable logistic regression model was built to study the effect of RTX dosage and time between latest rituximab and vaccination on response, adjusting for age and methotrexate use. After two-dose vaccination, the response rate was significantly better for patients receiving 200 mg (n = 31, 45%) rituximab compared with 1000 mg (n = 98, 26%; odds ratio 3.07, 95% CI 1.14-8.27) and for each additional month between latest rituximab and vaccination (OR 1.67, 1.39-2.01). Both increased time between latest rituximab infusion and complete vaccination, and 200 mg as latest dose were associated with a better response to COVID-19 vaccination and should be considered when trying to increase vaccine response after rituximab in RA patients. Netherlands Trial Register, https://www.trialregister.nl/, NL9342.


Cyclosporine as Therapy for Traumatic Brain Injury.
Drug development in traumatic brain injury (TBI) has been impeded by the complexity and heterogeneity of the disease pathology, as well as limited understanding of the secondary injury cascade that follows the initial trauma. As a result, patients with TBI have an unmet need for effective pharmacological therapies. One promising drug candidate is cyclosporine, a polypeptide traditionally used to achieve immunosuppression in transplant recipients. Cyclosporine inhibits mitochondrial permeability transition, thereby reducing secondary brain injury, and has shown neuroprotective effects in multiple preclinical models of TBI. Moreover, the cyclosporine formulation NeuroSTAT® displayed positive effects on injury biomarker levels in patients with severe TBI enrolled in the Phase Ib/IIa Copenhagen Head Injury Ciclosporin trial (NCT01825044). Future research on neuroprotective compounds such as cyclosporine should take advantage of recent advances in fluid-based biomarkers and neuroimaging to select patients with similar disease pathologies for clinical trials. This would increase statistical power and allow for more accurate assessment of long-term outcomes.


Oxygen detoxification in algal-invertebrate symbioses from the Great Barrier Reef.
Examination of 34 species of symbiotic invertebrates in four phyla has confirmed the generality of a direct relationship between chlorophyll concentration and the activities of superoxide dismutase and catalase, two enzymes involved in the detoxification of active oxygen. On a finer scale, activities of these enzymes also depend on the localization of the algal symbions (intracellular or extracellular) and hence on the extent to which photosynthetic O2 actually contacts animal cytoplasm, and on the solar irradiance experienced by the symbionts. Differences in SOD activity among organs of Tridacna crocea are not fully explained by local O2 levels but are further related to organ-specific retes of O2 consumption. This result is discussed in terms of known mechanisms of superoxide radical production in mitochondria and differences in O2 utilization concentrations among various organs in bivalve molluscs.


Integration of ethnic food into Swedish food rituals. The cultural fitness of tacos.
This paper explores the meaning of the Mexican dish tacos for Swedish consumers. As such, this study examines the relationship between ethnic food and food culture in light of contemporary changing food rituals. The results reveal that the Swedish food ritual of Friday dinner can be enacted through eating tacos. Friday dinner is a point in time and space at which family members gather, after a busy week following divergent schedules that keep them from eating together, and to which children's food preferences are central. Tacos fulfil all the requirements for a quick-to-cook yet social dish that enables hardworking but time-constrained families to eat together. The much-debated informal and fragmented character of food consumption in contemporary society is accommodated in the taco meal.


An evaluation of the Stihler 1FT 200 blood warmer.
The performance of the Stihler 1FT 200 blood warmer was evaluated at flow rates from 25 to 150 ml/minute and compared with that of the Hetotherm and Fenwal warmers. The Fenwal proved to be an efficient apparatus at all flow rates but the performance of the Hetotherm fell off slightly at higher flow rates. The Stihler 1FT 200 did not meet requirements for use in the operating room.


The use of modified glove-like abdominal flap for reconstruction of contracture following burns of dorsal hand and fingers: A case report.
Burn contracture has been a challenge for its acquired functional disabilities and deformities. Surgical reconstruction poses a significant challenge for optimal aesthetic and functional improvement. Super thin abdominal skin pedicle flap can be used, but it has only one pedicle from one site of abdomen and needs tissue expander for a larger defect. The use of modified glove-like abdominal flap has been stated to be an option mainly for the use on acute hand burn. In this study, application of the modified glove-like abdominal flap was applied to contracture of dorsal hand and fingers. A 39-year-old male patient with severe contracted hand, eight-month post-burn injury presented at outpatient clinic Santosa Central Hospital in 2017. Multiple series of surgeries were performed on this patient, consisting of released contracture, defect closure using a modified "glove-like" thin abdominal flap, and flap separation. Abdominal flap has been the commonly used technique but has the disadvantage of being bulky. Glove-like abdominal flap, a subcutaneous layer plane flap, can be performed simply, safely, and briefly. It has been published mainly for reconstruction for acute burn hand injuries, not for burn hand contracture. The use of modified glove abdominal flap technique for reconstruction in hand burn contracture gives a satisfactory result in terms of functional and aesthetic outcome and can be an option in reconstruction in contracted dorsal hand and fingers.


FDG PET/CT Imaging of Carotid Atherosclerosis.
Atherosclerosis is a complex inflammatory process and an integral component of myocardial infarction and stroke. Atherosclerotic plaques can be detected using ultrasonography, myocardial perfusion imaging, coronary angiography, multidetector computed tomography (CT), and MR imaging. These modalities assess the luminal encroachment of the plaques or the structural features. Imaging plaque biology in concert with plaque structure may provide important insights. PET scanning using (18)F fluorodeoxyglucose. ((18)F FDG-PET) is commonly combined with CT scanning to characterize oncological processes. This review examines the role of (18)F FDG-PET/CT imaging in the characterization of atherosclerotic plaque biology.


Wavelet-based artifact identification and separation technique for EEG signals during galvanic vestibular stimulation.
We present a new method for removing artifacts in electroencephalography (EEG) records during Galvanic Vestibular Stimulation (GVS). The main challenge in exploiting GVS is to understand how the stimulus acts as an input to brain. We used EEG to monitor the brain and elicit the GVS reflexes. However, GVS current distribution throughout the scalp generates an artifact on EEG signals. We need to eliminate this artifact to be able to analyze the EEG signals during GVS. We propose a novel method to estimate the contribution of the GVS current in the EEG signals at each electrode by combining time-series regression methods with wavelet decomposition methods. We use wavelet transform to project the recorded EEG signal into various frequency bands and then estimate the GVS current distribution in each frequency band. The proposed method was optimized using simulated signals, and its performance was compared to well-accepted artifact removal methods such as ICA-based methods and adaptive filters. The results show that the proposed method has better performance in removing GVS artifacts, compared to the others. Using the proposed method, a higher signal to artifact ratio of -1.625 dB was achieved, which outperformed other methods such as ICA-based methods, regression methods, and adaptive filters.


Phase variation of a beta-1,3 galactosyltransferase involved in generation of the ganglioside GM1-like lipo-oligosaccharide of Campylobacter jejuni.
Ganglioside mimicry by Campylobacter jejuni lipo-oligosaccharide (LOS) is thought to be a critical factor in the triggering of the Guillain-Barré and Miller-Fisher syndrome neuropathies after C. jejuni infection. The combination of a completed genome sequence and a ganglioside GM1-like LOS structure makes C. jejuni NCTC 11168 a useful model strain for the identification and characterization of the genes involved in the biosynthesis of ganglioside-mimicking LOS. Genome analysis identified a putative LOS biosynthetic cluster and, from this, we describe a putative gene (ORF Cj1139c), which we have termed wlaN, with a significant level of similarity to a number of bacterial glycosyltransferases. Mutation of this gene in C. jejuni NCTC 11168 resulted in a LOS molecule of increased electrophoretic mobility, which also failed to bind cholera toxin. Comparison of LOS structural data from wild type and the mutant strain indicated lack of a terminal beta-1,3-linked galactose residue in the latter. The wlaN gene product was demonstrated unambiguously as a beta-1,3 galactosyltransferase responsible for converting GM2-like LOS structures to GM1-like by in vitro expression. We also show that the presence of an intragenic homopolymeric tract renders the expression of a functional wlaN gene product phase variable, resulting in distinct C. jejuni NCTC 11168 cell populations with alternate GM1 or GM2 ganglioside-mimicking LOS structures. The distribution of wlaN among a number of C. jejuni strains with known LOS structure was determined and, for C. jejuni NCTC 12500, similar wlaN gene phase variation was shown to occur, so that this strain has the potential to synthesize a GM1-like LOS structure as well as the ganglioside GM2-like LOS structure proposed in the literature.


Protective effects of Capsicum fruits and their constituents on damage in TNF-α-stimulated human dermal fibroblasts.
Antioxidant and anti-inflammatory effects of natural products on skin cells have been proved to be effective in improving skin damage. Capsicum species contain capsaicinoids that have antioxidant and anti-inflammatory properties, and various subspecies are cultivated. In this study, the effects of four Capsicum fruits and major constituents on oxidative stress and inflammatory reactions were measured using human dermal fibroblasts (HDFs) to verify their effects on skin damage. The inhibitory effects of nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2 ) by cucumber hot pepper, red pepper (RDP), Shishito pepper (SSP), and Cheongyang pepper were determined in HDFs. RDP and SSP inhibited the production of NO, ROS, and PGE2 in tumor necrosis factor-alpha-stimulated HDFs. Additionally, SSP seeds restored tumor necrosis factor-alpha-induced increase in matrix metalloproteinase-1 and decreased procollagen I α1 (COLIA1). In high-performance liquid chromatography analysis of the capsaicinoids capsaicin (CAP) and dihydrocapsaicin (DHC), CAP was detected at a higher level than DHC in the peel and seeds of all four types of Capsicum fruits, and the total amount of capsaicinoids was the highest in SSP. CAP and DHC, which are major constituents of Capsicum fruits, also inhibited NO, ROS, and PGE2 and restored matrix metalloproteinase-1 and procollagen I α1. RDP and SSP were shown to have a significant protective effect on skin damage, including oxidative stress, inflammatory reactions, and reduction of collagens. Capsaicinoids CAP and DHC were proved as active constituents. This research may provide basic data for developing Capsicum fruits as ingredients to improve skin damage, such as inflammation and skin aging. © 2022 Society of Chemical Industry.


Enhanced patient retention after combination vs single modality treatment using hyaluronic acid filler and neuromodulator: A multicenter, retrospective review by The Flame Group.
It is believed that combination treatment with both neuromodulators (NM) and hyaluronic acid soft-tissue fillers (HA) results in superior aesthetic results and increased patient satisfaction compared to either treatment alone. To determine whether combined treatment with NM and HA leads to greater patient retention than treatment with NM or HA alone. This is a large, multi-center, retrospective review of patient retention rates from 7 aesthetic practices across 5 continents, incorporating over 2600 patients. Patient retention is interpreted as a surrogate marker for overall patient satisfaction. Retention rates were compared at 1, 3, and 5 years for patients who received NM only, HA only, or combination treatment with both NM and HA. Combination therapy significantly increased the probability of retention for each time point (1, 3, and 5 years) compared with NM alone (P < .0001) and HA alone (P < .0001). This large multicenter, global retrospective review demonstrates that patients who received combined HA and NM were more likely to be retained in the same practice over many years than those who received either treatment alone.


HHV-6 encoded small non-coding RNAs define an intermediate and early stage in viral reactivation.
Human herpesvirus 6A and 6B frequently acquires latency. HHV-6 activation has been associated with various human diseases. Germ line inheritance of chromosomally integrated HHV-6 makes viral DNA-based analysis difficult for determination of early stages of viral activation. We characterized early stages of HHV-6 activation using high throughput transcriptomics studies and applied the results to understand virus activation under clinical conditions. Using a latent HHV-6A cell culture model in U2OS cells, we identified an early stage of viral reactivation, which we define as transactivation that is marked by transcription of several viral small non-coding RNAs (sncRNAs) in the absence of detectable increase in viral replication and proteome. Using deep sequencing approaches, we detected previously known as well as a new viral sncRNAs that characterized viral transactivation and differentiated it from latency. Here we show changes in human transcriptome upon viral transactivation that reflect multiple alterations in mitochondria-associated pathways, which was supported by observation of increased mitochondrial fragmentation in virus reactivated cells. Furthermore, we present here a unique clinical case of DIHS/DRESS associated death where HHV-6 sncRNA-U14 was abundantly detected throughout the body of the patient in the presence of low viral DNA. In this study, we have identified a unique and early stage of viral activation that is characterized by abundant transcription of viral sncRNAs, which can serve as an ideal biomarker under clinical conditions.


Evaluation of Commercial Next-Generation Sequencing Bioinformatics Software Solutions.
Next-generation sequencing (NGS) diagnostics continue to expand rapidly in clinical medicine. An ever-expanding menu of molecular biomarkers is deemed important for diagnostic, prognostic, and therapeutic assessment in patients. The increasing role of NGS in the clinic is driven mainly by the falling costs of sequencing. However, the data-intensive nature of NGS makes bioinformatic analysis a major challenge to many clinical laboratories. Critically needed NGS bioinformatics personnel are hard to recruit and retain in small- to mid-size clinical laboratories. Also, NGS software often lacks the scalability necessary for expanded clinical laboratory testing volumes. Commercial software solutions aim to bridge the bioinformatics barrier via turnkey informatics solutions tailored specifically for the clinical workplace. Yet, there has been no systematic assessment of these software solutions thus far. This article presents an end-to-end vendor evaluation experience of commercial NGS bioinformatics solutions. Six different commercial vendor solutions were assessed systematically. Key metrics of NGS software evaluation to aid in the robust assessment of software solutions are described. Comprehensive feedback, provided by the TriCore Reference Laboratories molecular pathology team, enabled the final vendor selection. Many key lessons were learned during the software evaluation process, which are described herein. This article aims to provide a detailed road map for small- to mid-size clinical laboratories interested in evaluating commercial bioinformatics solutions available in the marketplace.


The detection of mutation in human diploid fibroblasts after mutagen treatment using non-selective cloning and enzyme electrophoresis.
In an attempt to study mutagenesis in human diploid fibroblasts, clones derived from mass cultures treated with mutagen have been examined by starch-gel electrophoresis for 43 different enzyme loci. A technique of mutagen treatment was devised which facilitated the cloning and which enabled the cells to be exposed to very high doses of EMS and MNNG. Two alterations in phenotype, presumably the result of mutation, were observed, one involving peptidase D (PEPD) and the other phosphoglucomutase (PGM1).


A paradox of temporal perception revealed by a stimulus oscillating in colour and orientation.
Psychophysical experiments with stimuli oscillating concurrently in colour and orientation revealed an apparently paradoxical dissociation between the perceived simultaneity of stimulus changes and the perceptual pairing of the events demarked by those changes. When subjects were required to report whether changes in colour and orientation were simultaneous, judgements were generally accurate within +/-10 ms. When subjects were required to report which colour was paired predominantly with which orientation, judgements showed a systematic temporal bias of up to 50 ms in favour of colour. This dissociation between different temporal judgements concerning the same stimulus sequence is not predicted by any of the current models of binding in conscious vision. We propose an account of these data based on the temporal response properties of colour- and orientation-selective model neurons such that the perceived pairing of visual attributes is modelled as the cross-correlation of time-varying neural response profiles and thus reflects both neuronal latencies and the rate of rapid adaptation rather than simply the temporal pattern of responses to stimulus transitions.


Identification of copy number variants with genome sequencing: Clinical experiences from the NYCKidSeq program.
Copy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first-tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0-21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype-driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes.


Resolution of symptoms after Heller's cardiomyotomy with DOR fundoplication versus endoscopic balloon dilatation in patients with achalasia Cardia at tertiary care hospital.
To compare improvement in symptoms following Heller's myotomy with Dor fundoplication and endoscopic pneumatic dilatation for the treatment of achalasia cardia. The prospective comparative study was conducted at the Department of Upper Gastroenterology and Minimally Invasive Surgery, Civil Hospital, Karachi, from February 2016 to January 2019, and comprised patients diagnosed with achalasia cardia on oesophageal manometry. The subjects were randomised into endoscopic pneumatic dilatation group A and laparoscopic Heller's myotomy with Dor fundoplication group B. Eckardt scores were compared between the groups at one-year follow-up. Data was analysed using SPSS 22. Of the 42 patients, 21(50%) were in each of the two groups. The mean age of patients in group A was 37±12.87 years compared to 34±8.59 years in group B. Treatment success in group A was 11(52%) compared to 21(76%) in group B. Eckardt scores between the groups were significant (p<0.001). Patient satisfaction was significantly more in group B (p<0.05). The efficacy of Heller's myotomy with Dor fundoplication was found to be greater than endoscopic pneumatic dilatation for improvement in dysphagia and overall patient satisfaction at one-year follow-up.


Electrophysiological heterogeneity of atrial fibrillation and local effect of propafenone in the human right atrium: analysis based on symbolic dynamics.
A recently developed algorithm that is based on symbolic dynamics and computation of the normalized algorithmic complexity (C(alpha)) was applied to basket-catheter mapping of the atrial fibrillation (AF). The aim of our study was to analyze the spatial distribution of the C(alpha) during AF and effects of propafenone on this distribution. During right atrial mapping in 25 patients with AF 31 intra-atrial and 1 surface bipolar channels were acquired. The anatomical location of the intra-atrial electrodes was defined fluoroscopically. C(alpha) was calculated for a moving window (size: 2000 points; step 500 points). Generated C(alpha) was analyzed within 10 minutes before and after administration of propafenone. The inter-regional C(alpha) distribution was analyzed using the Friedman-test (intra-individually) and Kruskall-Wallis-H-test (inter- individually). A value of p=0.05 was set for an error probability. Inter-regional C(alpha) differences were found in all patients (p<0.001). The right atrium could be divided in high- and low complexity areas according to individual patterns. A significant C(alpha) increase in cranio-caudal direction (with the exception of septum) was confirmed inter-individually (p<0.01). The administration of propafenone enlarged the areas of low complexity. This new method utilizing the combination of symbolic dynamics and adaptive power estimation can provide complex evaluation of the dynamics of AF in man. High-density mapping will be required for further evaluation of results.


Genetic modification of plant cell walls to enhance biomass yield and biofuel production in bioenergy crops.
Plant cell walls represent an enormous biomass resource for the generation of biofuels and chemicals. As lignocellulose property principally determines biomass recalcitrance, the genetic modification of plant cell walls has been posed as a powerful solution. Here, we review recent progress in understanding the effects of distinct cell wall polymers (cellulose, hemicelluloses, lignin, pectin, wall proteins) on the enzymatic digestibility of biomass under various physical and chemical pretreatments in herbaceous grasses, major agronomic crops and fast-growing trees. We also compare the main factors of wall polymer features, including cellulose crystallinity (CrI), hemicellulosic Xyl/Ara ratio, monolignol proportion and uronic acid level. Furthermore, the review presents the main gene candidates, such as CesA, GH9, GH10, GT61, GT43 etc., for potential genetic cell wall modification towards enhancing both biomass yield and enzymatic saccharification in genetic mutants and transgenic plants. Regarding cell wall modification, it proposes a novel groove-like cell wall model that highlights to increase amorphous regions (density and depth) of the native cellulose microfibrils, providing a general strategy for bioenergy crop breeding and biofuel processing technology.


Cover crops do not increase soil organic carbon stocks as much as has been claimed: What is the way forward?
When compared to virgin land (forest and grassland), croplands store significantly lower amounts of organic carbon (OC), mainly as a result of soil tillage, and decreased plant inputs to the soil over the whole year. Doubts have been expressed over how much reduced and zero tillage agriculture can increase OC in soils when the whole soil profile is considered. Consequently, cover-crops that are grown in-between crops instead of leaving soils bare appear as the "last man standing" in our quest to enhance cropland OC stocks. Despite the claim by numerous meta-analyses of a mean carbon sequestration rate by cover crops to be as high as 0.32 ± 0.08 ton C ha-1 year-1 , the present analysis showed that all of the 37 existing field studies worldwide only sampled to a depth of 30 cm or less and did not compare treatments on the basis of equivalent soil mass. Thirteen studies presented information on OC content only and not on OC stocks, had inappropriate controls (n = 14), had durations of 3 years or lower (n = 5), considered only one to two data points per treatment (n = 4), or used cover crops as cash crops (i.e., grown longer that in-between two crops) instead of catch crops (n = 2), which in all cases constitutes shortcomings. Of the remaining six trials, four showed non-significant trends, one study displayed a negative impact of cover crops, and one study displayed a positive impact, resulting in a mean OC storage of 0.03 ton ha-1 year-1 . Models and policies should urgently adapt to such new figure. Finally, more is to be done not only to improve the design of cover-crop studies for reaching sound conclusions but also to understand the underlying reasons of the low efficiency of cover crops for improved carbon sequestration into soils, with possible strategies being suggested.


Ischaemic strictures in patients treated with a low anterior resection and perioperative radiotherapy for rectal carcinoma.
In five (6 per cent) of 78 consecutive patients treated with an anterior resection for rectal carcinoma, a stenosis of the sigmoid colon just above the anastomosis was observed. Four patients had received preoperative radiotherapy over a period of 1 week to a total dose of 25.5 Gy and one patient had received postoperative radiotherapy (60 Gy) over a total of 8 weeks. The length of the stenosis varied from 4 to 120 cm. Two patients subsequently underwent reoperation with an abdominoperineal resection and three patients with a Hartmann procedure. In all patients the inferior mesenteric artery had been ligated close to the aorta. It is proposed that the stenosis may have been due to insufficient circulation in the marginal artery. This insufficiency may have been aggravated by the irradiation, as the retained part of the sigmoid colon was partly included in the irradiation target.


Effect of chronic alcohol consumption on ethanol and acetaldehyde metabolism.
Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase (ADH) pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system (MEOS). Since the major fraction of ethanol metabolism proceeds via ADH and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate MEOS pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Eventually, injury develops with alterations of the rough endoplasmic reticulum and structural and functional abnormalities of the mitochondria.


Do outcomes vary according to the source of admission to the pediatric intensive care unit?
To examine associations between mortality, length of stay, and the sources of admission to tertiary pediatric intensive care. A retrospective analysis of prospectively collected data. A tertiary medical center with a 16-bed medical-surgical intensive care unit and a 15-bed cardiac pediatric intensive care unit (PICU). All admissions from July 1, 1998, through June 30, 2004. Multivariable regression methods compared length of stay and mortality between the sources of PICU admission, controlling for multiple variables, including severity of illness. None. Of 8,897 eligible admissions, 74% were directly from the study hospital's emergency department or operating rooms, while 26% were from indirect sources, including the study hospital's wards (11%) or interhospital transfer from either non-PICU (12%) or PICU settings (3%). Compared with emergency department admissions, ward admissions had higher odds of mortality (odds ratio 1.65, 95% confidence interval 1.08-2.51), transfer admissions from non-PICU settings did not have elevated odds of mortality (odds ratio 0.80, 95% confidence interval 0.51-1.25), and inter-PICU transfer admissions had higher odds of mortality (odds ratio 1.43, 95% confidence interval 0.80-2.56), although not reaching statistical significance. Compared with emergency department admissions, ward admissions stayed almost 4 days longer in the PICU, while interhospital transfer admissions from non-PICU and PICU settings stayed 2 and 6 days longer, respectively. Outcomes of tertiary pediatric intensive care vary significantly by source of admission. Strategies aimed at reduction of mortality at the tertiary PICU should target transfer admissions from the hospital's wards and from PICUs of other hospitals.


Renal autotransplantation for managing a short upper ureter or after ex vivo complex renovascular reconstruction.
To report our contemporary experience with renal autotransplantation (AT), an established treatment for managing patients with a shortened ureter or renovascular disease, as despite its historical importance, AT remains an underused technique by urologists. All patients undergoing AT between 1997 and 2002 for a short ureter after ureteric injury and for renovascular disease were assessed by creatinine level and blood pressure before and after surgery, and antihypertensive drug use and complications. Eleven patients had AT for renovascular disease and four for ureteric injury. There was no statistical difference in creatinine levels or blood pressure before and after surgery in either group. Eight patients treated with AT for renovascular disease required less antihypertensive medication after surgery. Minor complications occurred in both groups and included a suture abscess, chronic wound pain, and transient acute tubular necrosis. One patient in the ureteric injury group required a transplant nephrectomy after renal vein thrombosis, and one in the renovascular group died from multi-organ system failure. AT remains a treatment option for patients with a short ureter after ureteric injury and in those with renovascular disease. Patients had stable renal function and blood pressure after surgery. Most patients treated for renovascular disease required less medication after AT. The procedure is associated with both minor and major complications, which must be considered before surgery.


Prolonged Induction of miR-212/132 and REST Expression in Rat Striatum Following Cocaine Self-Administration.
Chronic exposure to cocaine in vivo induces long-term synaptic plasticity associated with the brain's circuitry that underlies development of repetitive and automatic behaviors called habits. In fact, prolonged drug consumption results in aberrant expression of protein-coding genes and small regulatory RNAs, including miRNAs that are involved in synaptic plasticity and neuroadaptations. However, the mechanisms mediating cocaine use disorder are still not fully understood. The present study is designed to examine the expression of miR-124, miR-132, miR-134, and miR-212, as well as the levels of the Ago2, Pum2, and REST mRNAs and proteins implicated in their regulation. We applied rat cocaine self-administration (SA) and extinction training procedures with a yoked triad to assess the changes in the levels of four miRNAs and three protein-coding genes and corresponding proteins in the dorsal striatum. We demonstrated that elevated expression of mature miR-212 and miR-132 is long-lasting and persists in the drug-free period (till 10-day abstinence). Moreover, mRNA and protein of REST, a regulator of neuronal transcription, was raised selectively in cocaine self-administering rats and Ago2 transcript decreased after cocaine treatment. Unexpectedly, the expression level of Ago2 and Pum2 proteins changed only in the active cocaine-receiving animals. These results point out the important aspects of long-lasting alterations in microRNAs, genes, and protein expressions involved in the control of synaptic plasticity associated with reward and motivation learning related to cocaine addiction.


The early identification of poor treatment outcome in a women's weight loss program.
Research examining factors associated with program attrition or failure to lose weight during active treatment has yielded mixed findings. The goal of the current investigation was to confirm and extend prior research on the predictors and correlates of attrition and failure to lose weight during treatment. This investigation examined whether baseline characteristics, early weight loss, attendance, weight-related quality of life, confidence and difficulties with eating and exercise, and diet-related thoughts and feelings during the final week of treatment were associated with percentage change in body weight. Forty-four, obese, sedentary, postmenopausal women were recruited to participate in a 24-session weight loss intervention. Poor treatment outcome (i.e., percentage change in body weight) was significantly associated with several baseline characteristics including higher body mass index (BMI), greater fat and lower carbohydrate consumption, poor body image, and greater expectations for program success. Poor treatment outcome was also significantly associated with poor program attendance, unsatisfactory early weight loss, unsatisfactory improvements in weight-related quality of life, and lower self-control and self-confidence. By the end of active treatment, women with poor treatment outcome evidenced significantly higher levels of guilt and feelings of failure. The need for early identification and intervention with participants at risk for treatment failure is discussed.


CRISPRs in the human genome are differentially expressed between malignant and normal adjacent to tumor tissue.
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) have been identified in bacteria, archaea and mitochondria of plants, but not in eukaryotes. Here, we report the discovery of 12,572 putative CRISPRs randomly distributed across the human chromosomes, which we termed hCRISPRs. By using available transcriptome datasets, we demonstrate that hCRISPRs are distinctively expressed as small non-coding RNAs (sncRNAs) in cell lines and human tissues. Moreover, expression patterns thereof enabled us to distinguish normal from malignant tissues. In prostate cancer, we confirmed the differential hCRISPR expression between normal adjacent and malignant primary prostate tissue by RT-qPCR and demonstrate that the SHERLOCK and DETECTR dipstick tools are suitable to detect these sncRNAs. We anticipate that the discovery of CRISPRs in the human genome can be further exploited for diagnostic purposes in cancer and other medical conditions, which certainly will lead to the development of point-of-care tests based on the differential expression of the hCRISPRs.


Enhancing efficacy, safety, and convenience of immunotherapy: a workshop presentation.
To discuss issues in delivering appropriate allergen immunotherapy. Review of Immunotherapy Collegium II workshop presented at the 2005 Annual Meeting of the American College of Allergy, Asthma and Immunology. Topics discussed during Immunotherapy Collegium II. In the past, dosage schedules, levels, and rates of acceleration were linked to skin test results. The most recent published schedules for administration of immunotherapy do not reflect the initial reaction to the skin test, but leave it to the treating physician to factor in the results of testing with plans for administration in both increments and frequency. However, there are no official recommendations for physicians relevant to using a skin test to gauge patient sensitivity. Rather, allergists are advised to set up a maintenance concentrate and then make suitable dilutions when immunotherapy is initiated. Although recommendations are lacking regarding the use of a skin test to gauge patient sensitivity, official recommendations are clear in other areas of immunotherapy, such as the use of premedication. It is important that standard terms be adopted by all physicians who prescribe allergen immunotherapy and that modified allergens and/or oral immunotherapy be explored in the future to make immunotherapy more comfortable.