Does the Computed Tomography Hounsfield Units Change Predict Response to Perioperative Chemotherapy in Patients with Gastric Adenocarcinoma.
Purpose: We aimed to investigate whether Computed Tomography (CT) attenuation change is predictive of poor pathological response in patients with gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma who received perioperative fluorouracil (FU), leucovorin (LV), oxaliplatin, and docetaxel (FLOT) regimen. Methods: This trial was planned as a retrospective single-center study. In the neoadjuvant setting, patients received a regimen that includes docetaxel (50 mg/m2), oxaliplatin (85 mg/m2), and LV (200 mg/m2) with short-term infusional FU (2600 mg/m2 as a 24-hour infusion), on day 1 and administered every two weeks for four cycles. Patients were classified as response rates according to the CAP-TRG system (0-1 response or 2-3 response) after completing four cycles of the FLOT regimen. Results: In total, 108 patients with GC and GEJ adenocarcinoma were included in the study. In a univariate analysis, age, histologic grade, T stage, N stage, and change in attenuation were found to be the statistically significant factors (p = 0.034, p =0.038, p = 0.001, p =0.029, and p = 0.022, respectively). In a multivariate analysis, T4 tumors and a higher change in attenuation were found to be important factors associated with poor pathologic response (p = 0.027 and p = 0.038, respectively). Conclusion: Our results demonstrate that a higher decrease in CT attenuation and T4 tumors is associated with a poor response to perioperative FLOT chemotherapy in patients with GC and GEJ adenocarcinoma.


Evaluation of bronchial responsiveness by pharmacological challenges in asthma. Inhaled propranolol in comparison with histamine and methacholine.
Bronchial challenges with bronchoconstrictive drugs have supplied important information on some relevant pathophysiological aspects of bronchial asthma, i.e. nonspecific bronchial hyperresponsiveness. Until now histamine and methacholine have been the most widely used inhalation tests. Recently, propranolol, given by inhalation, has been proposed and evaluated for possible application as a bronchial provocation challenge both in clinical and experimental setting. In asthmatic subjects with bronchial hyperresponsiveness to histamine and methacholine, inhaled propranolol induces a dose-related bronchoconstriction. In a group of 25 asthmatic patients, the mean value of provocative doses, in mumoles of propranolol that causes a 20% drop in FEV1 (PD20FEV1), is thirteen times greater than that of methacholine. In the same study, there is no correlation between the bronchial responses to the two drugs. Moreover, none of 9 normal subjects of the control group responds to inhaled propranolol. The mechanisms of propranolol-induced bronchoconstriction are poorly understood. A cholinergic reflex is probably involved, but it is likely that propranolol has some different and rather peculiar pathways. Bronchial response to inhaled propranolol is a reliable, reproducible, safe, and well-tolerated method. Bronchoconstriction induced by propranolol appears to be a very promising technique in the investigation of the mechanisms of nonspecific bronchial hyperresponsiveness.


Visible and near-infrared emitting heterotrimetallic lanthanide-aluminum-sodium 12-metallacrown-4 compounds: discrete monomers and dimers.
The luminescence properties of two types of heterotrimetallic aluminum-lanthanide-sodium 12-metallacrown-4 compounds are presented here, LnNa(ben)4[12-MCAl(III)N(shi)-4] (LnAl4Na) and {LnNa[12-MCAl(III)N(shi)-4]}2(iph)4 (Ln2Al8Na2), where Ln = GdIII, TbIII, ErIII, and YbIII, MC is metallacrown, ben- is benzoate, shi3- is salicylhydroximate, and iph2- is isophthalate. The aluminum-lanthanide-sodium metallacrowns formed with benzoate are discrete monomers while, upon replacement of the benzoate with the dicarboxylate isophthalate, two individual metallacrowns can be joined to form a dimer. In the solid state, the terbium version of each structure type displays emission in the visible region, and the erbium and ytterbium complexes emit in the near-infrared. The luminescence lifetimes (τobs) and quantum yields have been collected under ligand excitation (QLLn) for both LnAl4Na monomers and Ln2Al8Na2 dimers. Several of these values tend to be shorter (luminescence lifetimes) and smaller (quantum yields) than the corresponding values recorded for the structurally similar gallium-lanthanide monomer and dimer 12-MC-4 molecules. However, the quantum yield value recorded for the visible emitting Tb2Al8Na2 dimer, 43.9%, is the highest value observed in the solid state to date for a TbIII based metallacrown.


Recurrent inflammatory pseudotumor of small bowel mesentery presenting as perforative peritonitis.
A 62-year-old man with recurrent inflammatory pseudotumor of the small bowel mesentery presented with perforative peritonitis; such a presentation has not been reported. The mass was excised successfully.


[Absence of (jaw)bone may be indicative of malignancy].
Following the loss of several molars in the left maxilla, a 73-year-old man asked his general dentist practitioner to restore his chewing efficiency. Initially, reconstruction of the left maxilla with an implant supported fixed partial denture was considered. However, intraorally a soft-tissue swelling was observed extending from the midline of the palate to the left buccal sulcus. A panoramic radiograph showed absence of bone between the oral cavity and the maxillary sinus. At first, after an incision biopsy and histopathologic examination, the condition was diagnosed as nodular fasciitis. However, because of subsequent aggressive growth of the lesion malignancy was suspected. Histopathological examination confirmed the assumption. The lesion appeared to be a sarcoma. The general diagnostic rule is that the aggressive behaviour of a lesion and the absence of a bony delineation on radiographic examination between the oral cavity and the maxillary sinus are signs of malignancy, until evidence to the contrary has been provided.


Monomorphic anti-HLA-A,B,C monoclonal antibodies detecting molecular subunits and combinatorial determinants.
Thirteen monoclonal antibodies that react with monomorphic determinants on the HLA-A,B,C-beta 2-microglobulin (beta 2m) molecule were characterized. Analysis of antibody activity included inhibition by papain-solubilized HLA antigens and free beta 2m, antibody binding to mouse-human somatic cell hybrids containing human chromosome 6 or 15, and antibody cross-reactivity with lymphocytes from nonhuman species. Two criteria for monomorphism were established: 1) equal inhibition or absorption of antibody activity by all papain-solubilized HLA antigens or cell lines of different HLA specificities tested; and 2) nonpolymorphic cross-reactivity within another species or subspecies. On the basis of soluble antigen inhibition and binding to somatic cell hybrids, 3 classes of antibodies were detected: anti-beta 2m, anti-heavy chain, and anti-complex (against a combinatorial determinant formed by heavy chain and beta 2m). Antibody cross-reaction patterns in nonhuman species were suggestive that these monomorphic antibodies detect a limited number of determinants, minimally one on each chain and 2 combinatorial determinants. Examination of the known primary sequences for HLA-A2, HLA-B7, H-2Kb, and mouse, rabbit and human beta 2m provides a molecular explanation for this limited mouse anti-HLA monomorphic antibody activity.


Flash chemistry using electrochemical method and microsystems.
This feature article provides a brief outline of the concept of flash chemistry for conducting extremely fast reactions in organic synthesis using electrochemically generated highly reactive species and microsystems.


Neck proprioception shapes body orientation and perception of motion.
This review article deals with some effects of neck muscle proprioception on human balance, gait trajectory, subjective straight-ahead (SSA), and self-motion perception. These effects are easily observed during neck muscle vibration, a strong stimulus for the spindle primary afferent fibers. We first remind the early findings on human balance, gait trajectory, SSA, induced by limb, and neck muscle vibration. Then, more recent findings on self-motion perception of vestibular origin are described. The use of a vestibular asymmetric yaw-rotation stimulus for emphasizing the proprioceptive modulation of motion perception from the neck is mentioned. In addition, an attempt has been made to conjointly discuss the effects of unilateral neck proprioception on motion perception, SSA, and walking trajectory. Neck vibration also induces persistent aftereffects on the SSA and on self-motion perception of vestibular origin. These perceptive effects depend on intensity, duration, side of the conditioning vibratory stimulation, and on muscle status. These effects can be maintained for hours when prolonged high-frequency vibration is superimposed on muscle contraction. Overall, this brief outline emphasizes the contribution of neck muscle inflow to the construction and fine-tuning of perception of body orientation and motion. Furthermore, it indicates that tonic neck-proprioceptive input may induce persistent influences on the subject's mental representation of space. These plastic changes might adapt motion sensitiveness to lasting or permanent head positional or motor changes.


The efficacy of 2 phytases on inositol phosphate degradation in different segments of the gastrointestinal tract, calcium and phosphorus digestibility, and bone quality of broilers.
The anti-nutritional effects of dietary inositol phosphates (IP6 through IP3) have been recognized in broiler chickens; however, inositol hexaphosphate (IP6) is more potent than the lower IP esters. The efficacies of 2 commercial phytases, a Buttiauxella sp. phytase (BSP) and a Citrobacter braakii phytase (CBP) at 500 and 1,000 FTU/kg, were studied on IP6-3 concentrations in the crop, proventriculus + gizzard, and distal ileum digesta, and ileal IP6 disappearance in broilers at day 22. Apparent ileal P and Ca digestibility, and bone quality at days 22 and 33 were also measured. Female Ross 308 broilers (n = 1,890; 30 birds × 7 diets × 9 replicates) were fed corn-soy-based crumbled diets. The 7 diets included a primary breeder recommendation-based positive control diet (PC); the PC marginally reduced in available P by 0.146% and Ca by 0.134% of the diet, (NC1) or moderately reduced by 0.174 and 0.159% of the diet, respectively (NC2). Other diets were the NC1 + BSP or CBP at 500 FTU/kg (NC1+500BSP and NC1+500CBP) and the NC2 + BSP or CBP at 1,000 FTU/kg (NC2+1,000BSP and NC2+1,000CBP). Each of the NC1 and NC2 had distal ileum IP6 disappearance similar to that of PC, but each had lower P digestibility and the majority of measured bone quality parameters than the PC. The ileal IP6 levels were decreased by 52.0 and 32.7% for NC1+500BSP and NC1+500CBP, respectively, relative to NC1 and by 73.6 and 50.9% for NC2+1,000BSP and NC2+1,000CBP, respectively, relative to NC2 (P < 0.001), with a similar effect for distal ileum IP6 disappearance. Overall, phytase in the NC diets increased P digestibility, and femur breaking strength and cortical bone mineral density at days 22 and 33. Overall, each of the phytases at each dose degraded IP6-3 across the gastrointestinal tract segments to increase P digestibility and the P and Ca utilization in bone. However, dietary BSP at 1,000 FTU/kg was most effective. Supplemental phytase degrades phytate to decrease the anti-nutritional effects in a dose- and phytase-dependent manner.


Period pain presenteeism: investigating associations of working while experiencing dysmenorrhea.
Although menstrual pain (dysmenorrhea) is common and can have detrimental effects on work and social functioning, little is known about how people manage it in their professional life. Existing evidence indicates that people with dysmenorrhea often engage in presenteeism, meaning they work despite experiencing symptoms and report perceptions of social stigma around menstruation. In this study, we investigated individual health-related factors, psychosocial factors, and work factors associated with period pain presenteeism in a cross-sectional survey study including N = 668 employed people with experiences of dysmenorrhea. Our results show that symptom severity, disclosure of menstrual pain to the leader, and remote work are directly associated with period pain presenteeism. We further found that the presence of medical diagnosis moderates the association between symptom severity and presenteeism. Disclosure to the leader was associated with leader gender, leader-member exchange (LMX), and the absence of a medical diagnosis, indicating a potential mediating effect. We did not, however, find the perceptions of public beliefs regarding the concealment of menstruation to be related to presenteeism or disclosure. Our findings have important implications for research on menstrual health and occupational health management practice.


Caffeine intake in eating disorders.
The current study compares caffeine consumption in females with an eating disorder and females without an eating disorder. Caffeine intake in three diagnostic groups (10 females with anorexia nervosa, 27 females with bulimia nervosa, and 42 females with binge eating disorder [BED]) was compared with caffeine intake in three comparison groups (n = 659 each). Data were obtained from a longitudinal study of Black and White girls. Three-day food records were examined for the years before the onset of the eating disorder, the onset year, and the years after the onset of the eating disorder. Data from the same years were used for the comparison groups. Caffeine intake increased over time between ages 9 and 19 years across all groups and this trend was not moderated by diagnostic status. For anorexia nervosa, relative to the non-eating disorder group, the proportional intake of caffeine from soda increased significantly before onset to onset to after onset and ingestion of chocolate-containing foods decreased sharply over time. Caffeine consumption in young girls with eating disorders differs from girls with no eating disorders only for anorexia nervosa, but not for bulimia nervosa or BED.


Acidic glycolipids from kidney of suncus (Insectivora).
Lipids were extracted from the kidney of house musk shrew (Suncus murinus), which belongs to the order Insectivora. Acidic glycosphingolipids were purified from lipid extracts by mild alkaline methanolysis followed by column chromatographies on DEAE-Sephadex and silica beads (Iatrobeads). Purified glycolipids were analyzed by thin-layer chromatography, mild acid hydrolysis, gas liquid chromatography of the methyl glycosides after methanolysis and gas chromatography-mass spectrometry of the partially methylated alditol acetates. The kidney of suncus was unique in that it contained ganglioside GM2 (NeuAc type, 28.7 nmol and NeuGc type, 15.8 nmol/g tissue) as the major ganglioside. GM4 (NeuAc) (2.6 nmol/g), and GM3 (NeuAc type, 11.5 nmol and NeuGc type, 8.7 nmol/g) were also present. The content (298.9 nmol/g) of galactosyl sulfatide (GalCer-I3-sulfate) was higher than the values reported previously for other animal species. The total amount of acidic groups in glycolipids of suncus kidney was compared with the values for the kidney of 4 placental mammals to obtain an allometric correlation: log Y = 0.266 + 0.780 log X where X designates body weight, kg and Y, total acidic groups, mumol. A highly significant correlation (r = 0.999) was obtained among values from 5 representative placental mammals which live in mesic environments, suggesting that acidic glycosphingolipids are essential for the kidney function.


Triazole Resistance in Aspergillus spp.: A Worldwide Problem?
Since the first description of an azole-resistant A. fumigatus strain in 1997, there has been an increasing number of papers describing the emergence of azole resistance. Firstly reported in the USA and soon after in Europe, it has now been described worldwide, challenging the management of human aspergillosis. The main mechanism of resistance is the modification of the azole target enzyme: 14-α sterol demethylase, encoded by the cyp51A gene; although recently, other resistance mechanisms have also been implicated. In addition, a shift in the epidemiology has been noted with other Aspergillus species (mostly azole resistant) increasingly being reported as causative agents of human disease. This paper reviews the current situation of Aspergillus azole resistance and its implications in the clinical setting.


Movement of tuberculosis patients and the failure to complete antituberculosis treatment.
The outcomes of tuberculosis (TB) patients who move before completing antituberculosis treatment have not been described. We studied a population-based cohort of 2,576 adult patients reported as having TB in California during 1993, including 147 patients who moved from one local health jurisdiction to another within California. We determined treatment outcomes (completed, defaulted, died, other) for 131 (89%) of these 147 patients. Patients who moved defaulted more often (relative risk [RR] = 5.5, 95% confidence interval [CI] = 4.1 to 7.4) than patients who did not move. Including these patients' treatment outcomes increased the known number of defaulters by 30%, from 141 to 183 persons. Additionally, diagnosis of TB in a state prison emerged as the strongest risk factor for defaulting from treatment. Patients who moved or defaulted were more likely to abuse drugs or alcohol, to be homeless or to be associated with congregate settings such as jails and prisons. On average, patients who defaulted after moving received less than three-quarters of their recommended treatment regimens. These patients may remain infectious or become infectious again. Our findings highlight the importance of ensuring complete treatment for TB patients who move; failure to do so will adversely affect patient health and TB control, especially in many high-risk populations and settings.


Regulation of intrarenal and circulating renin-angiotensin systems in severe heart failure in the rat.
Activation of the intrarenal renin-angiotensin system may contribute to the pathophysiology of heart failure by accelerating the generation of angiotensin II at local sites within the kidneys. Activation of the local intrarenal renin-angiotensin system occurs in rats and with mild heart failure. The aim of the present study was to examine components of the circulating as well as the intrarenal renin-angiotensin system in rats with severe heart failure. Six weeks after experimental myocardial infarction (heart failure, HF; n = 8) or sham operation (control, C; n = 6), haemodynamics and the circulating and intrarenal components of the renin-angiotensin system were studied. HF rats were characterised by large infarctions (scar tissue > 40% of the left ventricular circumference). In comparison to sham operated controls, large myocardial infarctions resulted in severe heart failure with decreased systolic [108(SEM 3) mm Hg v 132(3) in C; p < 0.001] and diastolic arterial blood pressure [83(3) mm Hg v 95(2) in C; p < 0.05], decreased left ventricular systolic pressure [109(3) mm Hg v 132(3) in C; p < 0.005] and increased left ventricular end diastolic pressure [27(2) mm Hg v 5(1) in C; p < 0.0001]. In rats with severe heart failure, the circulating renin-angiotensin system was activated, with an increase in plasma renin activity (3.5-fold, p < 0.05) and plasma angiotensin II concentration (threefold, p < 0.01). In parallel, the intrarenal renin-angiotensin system was activated in severe heart failure. Increases occurred in renal renin mRNA level (1.7-fold, p < 0.01), renal angiotensinogen mRNA level (1.8-fold, p < 0.05), and renal angiotensin II concentration (twofold, p < 0.05) compared to C. Intrarenal angiotensin II concentrations exceeded plasma levels by a factor of 50 and were positively correlated with renal angiotensinogen mRNA levels (r = 0.874, p < 0.001), suggesting that local synthesis is the major source of angiotensin II found in the kidney. The intrarenal renin-angiotensin system may be selectively activated in mild heart failure, while both circulating and intrarenal renin-angiotensin systems are induced as the extent of left ventricular function worsens.


ATR Inhibition Potentiates PARP Inhibitor Cytotoxicity in High Risk Neuroblastoma Cell Lines by Multiple Mechanisms.
Background: High risk neuroblastoma (HR-NB) is one the most difficult childhood cancers to cure. These tumours frequently present with DNA damage response (DDR) defects including loss or mutation of key DDR genes, oncogene-induced replication stress (RS) and cell cycle checkpoint dysfunction. Aim: To identify biomarkers of sensitivity to inhibition of Ataxia telangiectasia and Rad3 related (ATR), a DNA damage sensor, and poly (ADP-ribose) polymerase (PARP), which is required for single strand break repair. We also hypothesise that combining ATR and PARP inhibition is synergistic. Methods: Single agent sensitivity to VE-821 (ATR inhibitor) and olaparib (PARP inhibitor), and the combination, was determined using cell proliferation and clonogenic assays, in HR-NB cell lines. Basal expression of DDR proteins, including ataxia telangiectasia mutated (ATM) and ATR, was assessed using Western blotting. CHK1S345 and H2AXS129 phosphorylation was assessed using Western blotting to determine ATR activity and RS, respectively. RS and homologous recombination repair (HRR) activity was also measured by γH2AX and Rad51 foci formation using immunofluorescence. Results: MYCN amplification and/or low ATM protein expression were associated with sensitivity to VE-821 (p < 0.05). VE-821 was synergistic with olaparib (CI value 0.04-0.89) independent of MYCN or ATM status. Olaparib increased H2AXS129 phosphorylation which was further increased by VE-821. Olaparib-induced Rad51 foci formation was reduced by VE-821 suggesting inhibition of HRR. Conclusion: RS associated with MYCN amplification, ATR loss or PARP inhibition increases sensitivity to the ATR inhibitor VE-821. These findings suggest a potential therapeutic strategy for the treatment of HR-NB.


Suppression of the basic transcription element-binding protein in brain neuronal cultures inhibits thyroid hormone-induced neurite branching.
The molecular mechanisms underlying the effect of thyroid hormone (T(3)) on neurite outgrowth are unknown. We recently identified the small GC-box binding protein BTEB (basic transcription element-binding protein) as a T(3)-regulated gene in the developing rat brain. BTEB mRNAs are rapidly (by 1 h) up-regulated by T(3) in primary rat embryonic neuronal cultures. Antisense oligodeoxynucleotides (ODNs), added to the cultures, reduced by 60% the level of BTEB mRNA. Addition of BTEB antisense ODNs to the cultures, before the onset of neurite polarity, had no effect on neurite elaboration but significantly decreased, in a dose-dependent manner, the effect of T(3) on neurite branching. We then examined the effects of antisense ODNs on a thyroid hormone target neuronal population, i.e. the acetylcholinesterase-positive neurons after the onset of neurite polarity. Exposure to BTEB antisense ODNs completely abolished the effects of T(3) on neurite branching and on the elaboration of neuritic filopodia-like structures in acetylcholinesterase cells. By contrast, antisense ODNs did not alter the effect of T(3) on neurite length. Our results show that titration of BTEB levels by T(3) regulates the degree of neurite branching and that the T(3)-induced neurite elongation and the T(3)-induced neurite branching are regulated by distinct mechanisms.


Dietary effects on pancreatic exocrine function. Experiments on the isolated perfused rat pancreas.
Studies of the response of the isolated perfused rat pancreas to three doses of secretin (5.0, 10.0, 18.75 U/h) and CCK (0.6, 1.5, 2.4 U/h) show that a 35-day administration of a carbohydrate-rich (60% carbohydrate, 3% fat, 20% protein) or fat-rich (34% fat, 11.3% carbohydrate, 29.8% protein) diet increases the sensitivity of the gland to these hormones compared to a standard diet (50.5% carbohydrate, 4% fat, 19% protein). The maximal secretory flow on stimulation by secretin and on a combined stimulation by secretin (2.5 U/h) plus CCK (1.8 U/h) is significantly (p less than 0.05 and p less than 0.01, respectively) lower in both experimental diets than in controls, whereas the maximal protein and enzyme secretion is diminished only in the secretin plus CCK-stimulated pancreas of rats fed a fat-rich diet. A carbohydrate-rich diet results in a relative increase in amylase secretion and decrease in lipase and chymotrypsinogen output. Compared to controls, the fat-rich diet leads to a stronger secretion of lipase and chymotrypsinogen and to a reduced amylase secretion. This adaptation of the exocrine pancreatic function is rather due to changes in the organ itself than to an altered hormonal stimulation.


Cricothyroidotomy for long-term tracheal access. A prospective analysis of morbidity and mortality in 76 patients.
Cricothyroidotomy for long-term tracheal access was prospectively studied in 76 critically ill patients. Thirty patients (39%) survived and 46 (61%) died. Mean duration of follow-up computed in all survivors was 8.5 months. Postmortem examination of the airway was performed in 85% of the nonsurvivors. Five patients (7%) had major complications including one death, subglottic stenosis in two adolescent patients, reversible subglottic granulation with partial obstruction in one patient, and tracheomalacia in one patient. Minor complications occurred in 23 (30%) survivors. Eleven (28%) of the nonsurvivors examined post mortem had airway pathology, including ulceration, hemorrhage and abscess at the stoma or cuff site, subglottic erosion, and mucosal separation. There were no significant differences in any of the parameters studied between the group with and the group without airway pathology. The morbidity and mortality of cricothyroidotomy in adults are similar to that reported for tracheostomy. However, cricothyroidotomy should be avoided in children and adolescents because of the risk of subglottic stenosis.


Dynamic changes of proteases and protease inhibitors revealed by microarray analysis in CA3 and entorhinal cortex during epileptogenesis in the rat.
We investigated expression of genes involved in the proteolytic process during epileptogenesis in a rat model of temporal lobe epilepsy (TLE). In a previous microarray study we found prominent activation of this process, which reached highest expression during the acute and latent phase (1 week after SE) in CA3 and entorhinal cortex (EC). Detailed analysis shows differences in dynamics of the changes of several protease genes such as cathepsins, caspases, matrix metalloproteinases, and plasminogen activators. Most genes were acutely upregulated while others were mainly activated during the latent phase. Interestingly several proteolytic genes were still elevated in the chronic epileptic phase. Various protease inhibitors followed a similar time course. The identification of changes in the activation of genes involved in proteolysis at critical phases during epileptogenesis could point to potential time specific targets for intervention. The fact that several proteolytic genes were still activated in the chronic epileptic phase makes them interesting candidates to modify and slow down seizure progression.


Multi-Faceted Environmental Analysis to Improve the Quality of Anthropogenic Water Reservoirs (Paprocany Reservoir Case Study).
Maintaining good condition of dam reservoirs in urban areas seems increasingly important due to their valuable role in mitigating the effects of global warming. The aim of this study is to analyze possibilities to improve water quality and ecosystem condition of the Paprocany dam reservoir (highly urbanized area of southern Poland) using current data of the water parameters, historical sources, and DPSIR (Driver-Pressure-State-Impact-Response) and 3D modeling concerning human activity and the global warming effects. In its history Paprocany reservoir overcame numerous hydrotechnical changes influencing its present functioning. Also, its current state is significantly influenced by saline water from the coal mine (5 g L-1 of chlorides and sulphates) and biogenic elements in recreational area (about 70 mg L-1 of chlorate and to 1.9 mg L-1 Kjeldahl nitrogen) and in sediments (222.66 Mg of Kjeldahl nitrogen, 45.65 Mg of P, and 1.03 Mg of assimilable phosphorus). Concluding, the best solutions to improve the Paprocany reservoir water quality comprise: increasing alimentation with water and shortening the water exchange time, restoration of the 19th century water treatment plant, and wetlands and reed bed area revitalization. The study also proved the applicability of mathematical models in planning of the actions and anticipating their efficiency.


The Short Stem THA Provides Promising Results in Patients with Osteonecrosis of the Femoral Head.
The short stem prosthesis showed good results in patients with primary osteoarthritis. However there were afew studies about the short stem total hip arthroplasty (THA) in patients with osteonecrosis of thefemoral head (ONFH). To evaluate the clinical and radiographic results of the short stem THA in patients with ONFH. The authors hypothesized that the short stem THA would be a promising procedure for patients with ONFH. The authors reviewed 120 osteonecrotic hips in 93 patients who underwent THA with Metha® short stem between November 2010 and February 2013. The appearance of bone trabeculae development and radiolucent line was reviewed using Gruen's classification. The Harris hip score (HHS) was recorded at 6, 12, 24, and 36 monthspostoperative for evaluating the clinical results. The mean age of patients was 44.4 years (18-68) with the mean BMI of 22.7 (15.1-32.5, SD 3.5). The average follow-up period was 29.2 months (20-47). The mean HHS was significantly improved from 43.9 (22.7-74, SD 7.7) preoperatively to 97.7 (85.9-100, SD 2.7) at 6-month postoperatively (p < 0.01). The radiographic change around the stems showed bone trabeculae development at zone 1 (77 cases, 64.2%), 2 (27 cases, 22.5%), 3 (106 cases, 88.3%), 6 (120 cases, 100%), and 7 (115 cases, 95.8%). There was one case (0.8%) of 5 mm subsidence and the radiolucent line was observed in zone 1. There were six cases (5%) of intraoperativefemoralfractures and were treated with cerclage wires with nofurther subsidence observed There was one case (0.8%) of distal stem perforation that had stable bone ingrowth. No revision was required. The clinical and radiographic results of the short stem THA in patients with ONFH are generally satisfactory. Its design enables preservation of the bone stock and the bone trabeculae appear to confirm the assumption of proximal force transmission. The authors believe that the short stem THA is a promising procedure for patients with ONFH.


Argon laser iridotomy and surgical iridectomy in treatment of primary angle-closure glaucoma.
In an attempt to compare surgical peripheral iridectomy and laser iridotomy with regards to the long-term control of the intraocular pressure (IOP), analyses were carried out of the clinical records of 195 eyes of 149 primary angle-closure glaucoma patients who had undergone either peripheral iridectomy or laser iridotomy and were followed up for at least one year. One hundred and ten eyes underwent peripheral iridectomy and 85 eyes had laser iridotomy. The postoperative IOP not exceeding 20 mmHg was taken as the criterion for success. The iridectomized eyes showed no significant difference from those treated with laser iridotomy in 13 clinical factors, including age at treatment, sex, type of angle-closure glaucoma, preoperative mean IOP with medication, visual field, extent of peripheral anterior synechiae (PAS) and horizontal cup/disk (C/D) ratio. The rate of successful IOP control was obtained in 76.4% of the eyes in the peripheral iridectomy group and in 75.3% of the eyes in the laser iridotomy group. It appears that laser iridotomy is just as effective as surgical iridectomy in normalizing IOP. Discriminant analysis was done to derive a discriminant function consisting of a set of factors that will prognosticate the response of primary angle-closure glaucoma either to surgical iridectomy or to laser iridotomy. Four factors were demonstrated to be significant prognosticators. They were preoperative mean IOP with medication, visual field change, C/D ratio and PAS-index, in order of statistical significance. The discriminant function yielded the discriminant efficacy of 71.2% in overall cases.


Placenta mesenchymal stem cells differentiation toward neuronal-like cells on nanofibrous scaffold.
Introduction: Transplantation of stem cells with a nanofibrous scaffold is a promising approach for spinal cord injury therapy. The aim of this work was to differentiate neural-like cells from placenta-derived mesenchymal stem cells (PDMSCs) using suitable induction reagents in three (3D) and two dimensional (2D) culture systems. Methods: After isolation and characterization of PDMSCs, the cells were cultivated on poly-L-lactide acid (PLLA)/poly caprolactone (PCL) nanofibrous scaffold and treated with a neuronal medium for 7 days. Electron microscopy, qPCR, and immunostaining were used to examine the differentiation of PDMSCs (on scaffold and tissue culture polystyrene [TCPS]) and the expression rate of neuronal markers (beta-tubulin, nestin, GFAP, and MAP-2). Results: qPCR analysis showed that beta-tubulin (1.672 fold; P ≤ 0.0001), nestin (11.145 fold; P ≤ 0.0001), and GFAP (80.171; P ≤ 0.0001) gene expressions were higher on scaffolds compared with TCPS. Immunofluorescence analysis showed that nestin and beta-tubulin proteins were recognized in the PDMSCs differentiated on TCPS and scaffold after 7 days in the neuroinductive differentiation medium. Conclusion: Taken together, these results delegated that PDMSCs differentiated on PLLA/PCL scaffolds are more likely to differentiate towards diversity lineages of neural cells. It proposed that PDMSCs have cell subpopulations that have the capability to be differentiated into neurogenic cells.


A decrease in fasting FGF19 levels is associated with the development of non-alcoholic fatty liver disease in obese adolescents.
Fibroblast growth factor 19 (FGF19) is a hormone released from the small intestine; recently, it has emerged as an endocrine regulator of glucose and lipid metabolism. The aim of this study was to investigate the role of FGF19 in the development of nonalcoholic fatty liver disease (NAFLD). This study included 23 (17 boys) obese adolescents (mean age of 14.1 years) with NAFLD. The control group consisted of 34 (13 boys) obese peers with normal ultrasonographic imaging and normal liver function tests. The definition of NAFLD was based on clinical criteria: elevated alanine aminotransferase (>35 U/L) and liver steatosis features on ultrasound imaging. Serum FGF19 levels were measured in a fasting blood sample. The definition of insulin resistance was based on the homeostasis model assessment (HOMA) threshold: >2.5. There was a significant difference between mean FGF19 levels in patients with NAFLD and controls (142.2 vs. 206 pg/mL, p=0.04). Mean fasting FGF19 levels were decreased in insulin-resistant patients in comparison with the non-insulin-resistant group (155.0 vs. 221.0 pg/mL, p=0.05). There was an inverse correlation between FGF19 and alanine aminotransferase levels (R=-0.3, p<0.05) and triglycerides (R=-0.27, p<0.05). A decrease in fasting FGF19 is associated with the development of NAFLD in obese adolescents. A decrease in fasting FGF19 levels may be a new important risk factor for NAFLD and the metabolic syndrome in adolescents. Further studies are needed to explain whether exogenous delivery of FGF19 might be therapeutically beneficial.


Hydration in children.
Water supply is a basic public problem. In modern science, three periods with different approaches to define recommended water intake in adults can be distinguished. Pediatricians agree that hydration in children may be optimal only in breastfed infants. More data are required on the health effects of different hydration states and varying water intakes in particular age and gender groups to define optimal ranges of water intake. The fetus grows in an exceptionally well-hydrated environment. Water metabolism shows several peculiarities in preterm and term infants. Infant diarrhea remains a major topic of basic and clinical research. Water intoxication in infants, toddlers, and children is rare and can only be found in exceptional circumstances. Hydration status characterized by hyponatremia may play a role in the pathogenesis of febrile convulsions in toddlers. There is increasing indirect evidence that spontaneous drinking behavior of a population may be fixed and anchored in the age range of toddlers. Sex differences in hydration status are common, but not obligatory. What causes theses differences? What is behind the various circadian rhythms of urine osmolality in children? At what age and in what quantities can alcohol and caffeine consumption be tolerated? How can individual susceptibility be defined? Reflecting on the modern epidemic of obesity in children and adolescents, a public consensus concerning use and misuse of sweetened drinks seems mandatory. Dietary reference intakes of water refer to 24-hour intake. In nutritional counselling, food and meal-based dietary advice is primarily given. Young parents are confronted with a flood of advice of varying quality. Recommendations on fluid consumption should be collated and revised.


Comparison of ESI-MS/MS and APCI-MS methods for the quantification of folic acid analogs in C. elegans.
Folic acid (FA) plays a vital role in central metabolism, including the one carbon cycle, nucleotide, and amino acid biosynthesis. The development of sensitive, accurate analytical methods to measure FA intermediates in tissues is critical to understand their biological roles in diverse physiological and pathological contexts. Here, we developed a highly sensitive method for the simultaneous quantification of FA intermediates in the nematode Caenorhabditis elegans as a model to dissect metabolic networks. The method was further validated by analyzing the worm folate pool upon RNAi knockdown of the dihydrofolate reductase gene dhfr-1. Comparative mass spectrometry behavior of the FA analogs using two different ion sources, electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), revealed ESI-MS/MS to be more sensitive, but APCI-MS provided more detailed structure inferences, which can elucidate chemical investigation and synthesis of FA analogs. Finally, we report on the use of in vitro oxidation coupled with high-resolution mass spectrometry as a tool to discover new endogenous FA derivatives in the nematode.


Wnt/Yes-Associated Protein Interactions During Neural Tissue Patterning of Human Induced Pluripotent Stem Cells.
Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests. However, the interactions between Wnt and YAP expression for neural lineage commitment of hiPSCs remain poorly explored. The objective of this study is to investigate the effects of Wnt signaling and YAP expression on the cellular population in three-dimensional (3D) neural spheroids derived from hiPSCs. In this study, Wnt signaling was activated using CHIR99021 for 3D neural spheroids derived from human iPSK3 cells through embryoid body formation. Our results indicate that Wnt activation induces nuclear localization of YAP and upregulates the expression of HOXB4, the marker for hindbrain/spinal cord. By contrast, the cells exhibit more rostral forebrain neural identity (expression of TBR1) without Wnt activation. Cytochalasin D was then used to induce cytoplasmic YAP and the results showed the decreased HOXB4 expression. In addition, the incorporation of microparticles in the neural spheroids was investigated for the perturbation of neural patterning. This study may indicate the bidirectional interactions of Wnt signaling and YAP expression during neural tissue patterning, which have the significance in neurological disease modeling, drug screening, and neural tissue regeneration.


[Mycosis of the maxillary sinus].
In the structure of morbidity and mortality has significantly increased the role of mycoses. The increase in their spread is due not only to the improvement of the quality of diagnosis, but also the emergence of new strains resistant to previously used antifungal drugs, a significant change in the immune status of the population. In addition to environmental factors, it is important to introduce modern methods of treatment that increase survival in the whole spectrum of diseases. This situation can't affect the structure of diseases of ENT organs: the number of mycoses has increased significantly in recent decades. The issues of diagnosis and treatment of mycoses of the paranasal sinuses continue to be an urgent problem of otorhinolaryngology. The reason for this is a number of difficulties associated with the diagnosis: the absence of specific symptoms of the disease, the possible secondary nature of the attachment of fungal infection against the background of bacterial lesions, transient carrier of infection, technical difficulties and errors in the study of biomaterial with insufficient standardization of microbiological methods. Our report is devoted to the clinical case of aspergillosis of the maxillary sinus and a review of the literature on this issue, which in our opinion can be very interesting to the medical community.


The future perspectives of natural materials for pulmonary drug delivery and lung tissue engineering.
Search for new, functional biomaterials that can be used to synergistically deliver a drug, enhance its adsorption and stimulate the post-injury recovery of tissue function, is one of the priorities in biomedicine. Currently used materials for drug delivery fail to satisfy one or more of these functionalities, thus they have limited potential and new classes of materials are urgently needed. Natural materials, due to their origin, physical and chemical structure can potentially fulfill these requirements and there is already strong evidence of their usefulness in drug delivery. They are increasingly utilized in various therapeutic applications due to the obvious advantages over synthetic materials. Particularly in pulmonary drug delivery, there have been limitations in the use of synthetic materials such as polymers and lipids, leading to an increase in the use of natural and protein-based materials such as silk, keratin, elastin and collagen. Literature search in each specialized field, namely, silk, keratin and collagen was conducted, and the benefits of each material for future application in pulmonary drug delivery are highlighted. The natural materials discussed in this review have been well established in their use for other applications, yet further studies are required in the application of pulmonary drug delivery. The properties exhibited by these natural materials seem positive for their application in lung tissue engineering, which may allow for more extensive testing for validation of pulmonary drug delivery systems.


Inhibitory potential of strepthonium A against Shiga toxin production in enterohemorrhagic Escherichia coli (EHEC) strain EDL933.
The production of shiga toxin (Stx) is a critical step in the establishment and progress of enterohemorrhagic Escherichia coli (EHEC) infections. The possible release of Stx from dead and dying bacteria, and the risk of resistance development have restricted the usage of antibiotics against EHEC. The chlorinated quaternary ammonium compound, strepthonium A, was isolated from the culture of Streptomyces sp. SBT345 that was cultivated from the Mediterranean sponge Agelas oroides. The structure was elucidated and confirmed by spectroscopic analyses including 1D and 2D NMR, ESI-HRMS, as well as ESI-HRMS2. Strepthonium A follows Lipinski's rule of five with respect to its molecular weight, CLogP values and the number of hydrogen acceptors and donors. Verotoxin ELISA assay demonstrated that Strepthonium A reduced the Stx production in EHEC strain EDL933 at 80 μM concentration without growth inhibition. This study demonstrates the potential of strepthonium A in restraining the production of Stx in EHEC infections.


Relating Metabolism Suppression and Nucleation Probability During Supercooled Biopreservation.
Aqueous supercooling provides a method by which to preserve biological matter at subfreezing temperatures without the deleterious effects of ice formation. The extended longevity of the preserved biologic is a direct result of a reduction in the rate of metabolism with decreasing temperature. However, because the nucleation of ice from a supercooled solution is a stochastic process, supercooled preservation carries the risk of random ice nucleation. Theoretical supercooled biopreservation research to date has largely treated these biological and thermophysical phenomena separately. Here, we apply a statistical model of stochastic ice nucleation to demonstrate how the possible reduction in metabolic rate is inherently related to supercooling stability (i.e., the likelihood of ice nucleation). We develop a quantitative approach by which to weigh supercooling stability versus potential metabolic reduction, and further show how the stability-metabolism relationship varies with system size for two assumed modes of nucleation. Ultimately, this study presents a generalizable framework for the informed design of supercooled biopreservation protocols that considers both phase transformation kinetics and biochemical or biophysical kinetics.


DELAYED TXA AFTER TBI IMPEDES LEARNING, MEMORY; EARLY TXA IS FAVORABLE BUT NOT IN SHAM ANIMALS.
Early but not late tranexamic acid (TXA) after TBI preserves blood-brain-barrier integrity, but it is unclear if and how dose timing affects cognitive recovery beyond hours post-injury. We hypothesized that early (1 h post-TBI) but not late (24 h post-TBI) TXA administration improves cognitive recovery for 14 days. CD1 male mice (n = 25) were randomized to severe TBI (Injury, [I] by controlled cortical impact) or sham craniotomy (S) followed by IV saline at 1 h (placebo, P1) or 30 mg/kg TXA at 1 h or 24 h (TXA1, TXA24). Daily body weights, Garcia Neurological Test (GNT) scores, brain/lung water content and Morris water maze exercises quantifying swimming traffic in the platform quadrant (Z1) & platform area (Z5) were recorded for up to 14 days. Among injured groups, I + TXA1 demonstrated fastest weight gain for 14 days and only I + TXA1 showed rapid (day 1) normalization of GNT (p = 0.01 vs. I + P1, I + TXA24). In cumulative spatial trials, compared to I + TXA1, I + TXA24 hindered learning (distance to Z5 and % time in Z1: p < 0.05). Compared to I + TXA1, I + TXA24 showed poorer memory with less Z5 time (0.51 vs 0.16 s, p < 0.01) and Z5 crossing frequency. Unexpectedly, TXA in uninjured animals (S + TXA1) displayed faster weight gain, but inferior learning and memory. Early TXA appears beneficial for cognitive and behavioral outcomes following TBI, though administration 24 h post-injury consistently impairs cognitive recovery. TXA in sham animals may lead to adverse effects on cognition.


[Carcinoma spinocellulare in erythematosus].
Case report on a 50-year-old man suffering from discoid lupus erythematosus since about 20 years. The development of a tumor of the left lower leg within a l. e. area, which turned out to be a squamous-cell carcinoma, had been noticed since two years. One year after tumor excision our patient died of multiple metastases. This case demonstrates the rare formation of a squamous-cell-carcinoma "in erythematode ".


Lymphocyte DNA damage and plasma antioxidant status in Korean subclinical hypertensive patients by glutathione S-transferase polymorphism.
Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of xenobiotics by conjugating substances with glutathione. The aim of this study is to assess the antioxidative status and the degree of DNA damage in the subclinical hypertensive patients in Korea using glutathione S-transferase polymorphisms. We examined whether DNA damage and antioxidative status show a difference between GSTM1 or GSTT1 genotype in 227 newly diagnosed, untreated (systolic blood pressure (BP) ≥ 130 mmHg or diastolic BP ≥ 85 mmHg) subclinical hypertensive patients and 130 normotensive subjects (systolic BP < 120 mmHg and diastolic BP < 80 mmHg). From the blood of the subjects, the degree of the DNA damage in lymphocyte, the activities of erythrocyte superoxide dismutase, the catalase, and the glutathione peroxidase, the level of glutathione, plasma total radical-trapping antioxidant potential (TRAP), anti-oxidative vitamins, as well as plasma lipid profiles and conjugated diene (CD) were analyzed. Of the 227 subjects studied, 68.3% were GSTM1 null genotype and 66.5% were GSTT1 null genotype. GSTM1 null genotype had an increased risk of hypertension (OR: 2.104, CI: 1.38-3.35), but no significant association in GSTT1 null genotype (OR 0.982, CI: 0.62-1.55). No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and plasma TRAP, CD, lipid profiles, and GSH levels were observed between GSTM1 or GSTT1 genotype. Plasma levels of α-tocopherol increased significantly in GSTT1 wild genotype (P < 0.05); however, plasma level of β-carotene increased significantly in GSTT1 null genotype (P < 0.01). DNA damage assessed by the Comet assay was significantly higher in GSTM1 null genotype than wild genotype (P < 0.05). These results confirm the association between GSTM1 null genotype and risk of hypertension as they suggest that GSTM1 null genotype leads to an increased oxidative stress compared with wild genotype.


Select bladder smooth muscle cell functions were enhanced on three-dimensional, nano-structured poly(ether urethane) scaffolds.
Bladder wall resection is often required as a treatment for invasive bladder cancer. When this happens, a suitable replacement material is needed. The present study, therefore, created three-dimensional, porous, nano-structured poly(ether urethane) (PU) matrices for use as bladder tissue-engineering scaffolds. Select cytocompatibility experiments (specifically adhesion and long-term growth studies) were performed on these scaffolds using human bladder smooth muscle cells (BdSMCs). In addition, the amount of total collagen and elastin present in each cell-seeded scaffold was determined since the production of these extracellular matrix (ECM) proteins is essential for the health and survival of cells and for the functionality of the replaced organ. Finally, to better understand how these scaffolds and resident cells would perform in the complex mechanical environment of the bladder wall, scaffolds and cells were subjected to 10 cmH2O pressure using a computer-controlled pressure chamber. Results provided evidence that compared to conventionally used, micro-dimensional PU scaffolds, the novel, nanodimensional scaffolds created in this research increased cell adhesion, growth, and ECM protein production. Additionally, scaffolds and resident cells were not affected by exposure to 10 cmH2O pressure (compared to controls maintained under atmospheric conditions). These results are promising and provide evidence that the nano-dimensional PU scaffolds created in this research are suitable bladder replacement materials that may outperform materials currently used for such purposes.


Three-Dimensional Structure from Single Two-Dimensional Diffraction Intensity Measurement.
Conventional three-dimensional (3D) imaging methods require multiple measurements of the sample in different orientation or scanning. When the sample is probed with coherent waves, a single two-dimensional (2D) intensity measurement is sufficient as it contains all the information of the 3D sample distribution. We show a method that allows reconstruction of 3D sample distribution from a single 2D intensity measurement, at the z resolution exceeding the classical limit. The method can be practical for radiation-sensitive materials, or where the experimental setup allows only one intensity measurement.


Monoclonal antibody therapy of human cancer: taking the HER2 protooncogene to the clinic.
The HER2 protooncogene encodes a 185-kDa transmembrane protein (p185HER2) with extensive homology to the epidermal growth factor (EGF) receptor. Clinical and experimental evidence supports a role for overexpression of the HER2 protooncogene in the progression of human breast, ovarian, and non-small cell lung carcinoma. These data also support the hypothesis that p185HER2 present on the surface of overexpressing tumor cells may be a good target for receptor-targeted therapeutics. The anti-p185HER2 murine monoclonal antibody (muMAb) 4D5 is one of over 100 monoclonals that was derived following immunization of mice with cells overexpressing p185HER2. The monoclonal antibody is directed at the extracellular (ligand binding) domain of this receptor tyrosine kinase and presumably has its effect as a result of modulating receptor function. In vitro assays have shown that muMAb 4D5 can specifically inhibit the growth of tumor cells only when they overexpress the HER2 protooncogene. MuMAb 4D5 has also been shown to enhance the TNF-alpha sensitivity of breast tumor cells that overexpress this protooncogene. Relevant to its clinical application, muMAb 4D5 may enhance the sensitivity of p185HER2-overexpressing tumor cells to cisplatin, a chemotherapeutic drug often used in the treatment of ovarian cancer. In vivo assays with a nude mouse model have shown that the monoclonal antibody can localize at the tumor site and can inhibit the growth of human tumor xenografts which overexpress p185HER2. Modulation of p185HER2 activity by muMAb 4D5 can therefore reverse many of the properties associated with tumor progression mediated by this putative growth factor receptor. Together with the demonstrated activity of muMAb 4D5 in nude mouse models, these results support the clinical application of muMAb 4D5 for therapy of human cancers characterized by the overexpression of p185HER2.


The origin of global and macrocyclic aromaticity in porphyrinoids.
The global and macrocyclic aromaticity of porphyrinoids was characterized using our graph theory of aromaticity. The sequential line plots of topological resonance energy (TRE) against the number of π-electrons (N(π)) for different porphyrinoids are similar with four major extrema to those for five-membered heterocycles. This supports the view that five-membered rings are the main origin of global aromaticity in porphyrinoids. Macrocyclic circuits contribute significantly to macrocyclic π-circulation but modestly to global aromaticity. Macrocyclic aromaticity/antiaromaticity in oligopyrrolic macrocycles can be predicted by formally applying Hückel's [4n + 2] rule to an annulene-like main macrocyclic conjugation pathway (MMCP). This bridged annulene model can be justified by examining the contribution of individual macrocyclic circuits to macrocyclic aromaticity. A Hückel-like rule of macrocyclic aromaticity was found for porphyrinoid species.


The quest for biomarkers in IBS-where should it lead us?
Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder which represents a major cost to health-care services. The diagnosis of IBS is currently performed by means of symptom-based diagnostic criteria, but there has been an ongoing interest in developing biomarkers which could simplify the diagnosis and/or evaluating the effect of treatments. This article reviews the current literature concerning the proposed biomarkers including those of altered gut motility, of visceral hypersensitivity, of abnormal brain mechanisms, of serum, fecal and mucosal inflammation and of increased intestinal permeability.


A comparison of salivary calcium, phosphate, and alkaline phosphatase in children with severe, moderate caries, and caries free in Tehran's kindergartens.
The most common dental disease in childhood is dental caries. This study was carried out to recognize the components of saliva which are protective factors in children to evaluate and predict caries susceptible and caries resistant individuals. Unstimulated whole saliva was obtained from 75 children aged 3-5 years. They divided into three groups: decayed missing and filled teeth (dmft) > 6 (severe caries), 1 P > 0.05 ). Although the results showed that salivary phosphate and alkaline phosphatase in caries free group and calcium in the group with severe caries were somewhat more than those in other groups. Despite of the results of the present study, the relationship between salivary components and caries rate in children remains controversial. So more studies are necessary to achieve some practical criteria for predicting dental caries, recognition of susceptible persons, and finally prevention of caries in children.


A multi-protease, multi-dissociation, bottom-up-to-top-down proteomic view of the Loxosceles intermedia venom.
Venoms are a rich source for the discovery of molecules with biotechnological applications, but their analysis is challenging even for state-of-the-art proteomics. Here we report on a large-scale proteomic assessment of the venom of Loxosceles intermedia, the so-called brown spider. Venom was extracted from 200 spiders and fractioned into two aliquots relative to a 10 kDa cutoff mass. Each of these was further fractioned and digested with trypsin (4 h), trypsin (18 h), pepsin (18 h), and chymotrypsin (18 h), then analyzed by MudPIT on an LTQ-Orbitrap XL ETD mass spectrometer fragmenting precursors by CID, HCD, and ETD. Aliquots of undigested samples were also analyzed. Our experimental design allowed us to apply spectral networks, thus enabling us to obtain meta-contig assemblies, and consequently de novo sequencing of practically complete proteins, culminating in a deep proteome assessment of the venom. Data are available via ProteomeXchange, with identifier PXD005523.


Characterization of a split respiratory pathway in the wheat "take-all" fungus, Gaeumannomyces graminis var. tritici.
This article describes the first detailed analysis of mitochondrial electron transfer and oxidative phosphorylation in the pathogenic filamentous fungus, Gaeumannomyces graminis var. tritici. While oxygen consumption was cyanide insensitive, inhibition occurred following treatment with complex III inhibitors and the alternative oxidase inhibitor, salicylhydroxamic acid (SHAM). Similarly, maintenance of a Deltapsi across the mitochondrial inner membrane was unaffected by cyanide but sensitive to antimycin A and SHAM when succinate was added as the respiratory substrate. As a result, ATP synthesis through complex V was demonstrated to be sensitive to these two inhibitors but not to cyanide. Analysis of the cytochrome content of mitochondria indicated the presence of those cytochromes normally associated with electron transport in eukaryotic mitochondria together with a third, b-type heme, exhibiting a dithionite-reduced absorbance maxima at 560 nm and not associated with complex III. Antibodies raised to plant alternative oxidase detected the presence of both the monomeric and dimeric forms of this oxidase. Overall this study demonstrates that a novel respiratory chain utilizing the terminal oxidases, cytochrome c oxidase and alternative oxidase, are present and constitutively active in electron transfer in G. graminis tritici. These results are discussed in relation to current understanding of fungal electron transfer and to the possible contribution of alternative redox centers in ATP synthesis.


Herpesvirus 6 glycoproteins B (gB), gH, gL, and gQ are necessary and sufficient for cell-to-cell fusion.
The human herpesvirus 6 (HHV-6) envelope glycoprotein gH/gL/gQ1/gQ2 complex associates with host cell CD46 as its cellular receptor. Although gB has been suggested to be involved in HHV-6 infection, its function in membrane fusion has remained unclear. Here, we have developed an HHV-6A (strain GS)and HHV-6B (strain Z29) virus-free cell-to-cell fusion assay and demonstrate that gB and the gH/gL/gQ1/gQ2 complex are the minimum components required for membrane fusion by HHV-6.


Equine ovarian tissue viability after cryopreservation and in vitro culture.
Ovarian tissue cryopreservation allows the preservation of the female fertility potential for an undetermined period. The objectives of this study were to compare the efficiency of cryoprotective agents (CPAs; dimethyl sulfoxide, DMSO; ethylene glycol, EG; and propylene glycol, PROH) using slow-freezing and vitrification methods, and evaluate the viability of cryopreserved equine ovarian tissue after 7 days of culture. Fresh and cryopreserved ovarian fragments were evaluated for preantral follicle morphology, stromal cell density, EGFR, Ki-67, Bax, and Bcl-2 protein expression, and DNA fragmentation. Vitrification with EG had the highest rate of morphologically normal preantral follicles, while DMSO had the lowest (76.1 ± 6.1% and 40.9 ± 14.8%, respectively; P < 0.05). In slow-freezing, despite that DMSO had the highest percentage of morphologically normal follicles (77.7 ± 5.8%), no difference among the CPAs was observed. Fluorescence intensity of EGFR and Ki-67 was greater when vitrification with EG was used. Regardless of the cryopreservation treatment, DMSO had the highest (P < 0.05) Bax/Bcl-2 ratio; however, DNA fragmentation was similar (P > 0.05) among treatments after thawing. After in vitro culture, the percentage of normal follicles was similar (P > 0.05) between slow-freezing and vitrification methods; however, vitrification had greater (P < 0.05) stromal cell density than slow-freezing. In summary, equine ovarian tissue was successfully cryopreserved, increasing the viability of the cells in the ovarian tissue after thawing when using DMSO and EG for slow-freezing and vitrification methods, respectively. Therefore, these results are relevant for fertility preservation programs.


Single-Cell RNA-Seq Reveals Developmental Origins and Ontogenetic Stability of Neurexin Alternative Splicing Profiles.
Neurexins are key synaptic organizers that are expressed in thousands of alternatively spliced isoforms. Because transsynaptic neurexin interactions with different postsynaptic molecules are largely isoform dependent, a cell type-level census of different neurexin isoforms could predict molecular interactions relating to synapse identity and function. Using single-cell transcriptomics to study the origin of neurexin diversity in multiple murine mature and embryonic cell types, we have discovered shared neurexin expression patterns in developmentally related cells. By comparing neurexin profiles in immature embryonic neurons, we show that neurexin profiles are specified during early development and remain unchanged throughout neuronal maturation. Thus, our findings reveal ontogenetic stability and provide a cell type-level census of neurexin isoform expression in the cortex.


The effect of NLRP inflammasome on the regulation of AGEs-induced inflammatory response in human periodontal ligament cells.
Diabetes influences the frequency and development of periodontitis. Inflammation of human periodontal ligament cells (HPDLCs) participates in this pathologic process. Hence, this study aims to explore whether advanced glycation end products (AGEs), by-products of diabetes, could exaggerate inflammation induced by muramyl dipeptide (MDP) in HPDLCs, and whether nucleotide-binding oligomerization domain-like receptors (NLRs) signaling pathway was involved. Human periodontal ligament cells were pre-treated with 100 μg/mL AGEs for 24 hours and stimulated with 10 μg/mL MDP for 24 hours. IL-6, IL-1β, and RAGE were detected, and the activation of NF-κB signaling pathway was observed. The expression of NLRs was evaluated with or without silencing RAGE or blocking NF-κB pathway under AGEs stimulation. Statistical analyses were performed by using independent sample t test. Advanced glycation end products induced significant increase of inflammatory cytokines in HPDLCs (P < 0.05). Results of western blot (WB) showed that after 45 minutes stimulation of AGEs, p-p65/p65 ratio peaked; AGEs promoted the expression of NLRP1, NLRP3, and apoptosis-associated speck-like protein containing a CARD (ASC). After silencing RAGE or blocking NF-κB pathway, the up-regulation of NLRs protein caused by AGEs was attenuated. Additionally, AGEs pre-treatment could enhance the inflammatory response of MDP and the expression of NLRs, which were demonstrated by more expression of IL-6, IL-1β, NOD2, NLRP1, NLRP3, and ASC. Advanced glycation end products induced inflammatory response in HPDLCs via NLRP1-inflammasome and NLRP3-inflammasome activation in which NF-κB signal pathway was involved. Besides, AGEs promoted the inflammatory response of MDP via NOD2, NLRP1-inflammasome, and NLRP3-inflammasome.


Large-diameter metal-on-metal cementless total hip arthroplasty in the elderly.
To evaluate the clinical effectiveness and complications of large-diameter metal-on-metal prostheses, particularly in the elderly, we performed cementless total hip arthroplasty (THA) using metal-on-metal prostheses with large-diameter femoral heads (mean, 45 mm) in 59 patients (average age, 75.1 years) between January 2004 and December 2005. All procedures were performed using a posterolateral approach and spinal anesthesia. Average follow-up was 65 months. Pre- and postoperative Harris Hip Scores and SF-36 questionnaire results were recorded for all patients to evaluate the level of pain relief, improvement in physical function, and changes in quality of life. Postoperative radiographic images were used to document areas of osteolysis and probable aseptic loosening. Average preoperative Harris Hip Score was 36.1±5.7, compared to 69.4±8.3 at last follow-up (P<.01). Average preoperative SF-36 score was 33.6±7.4, compared to 71.8±6.4 at last follow-up (P<.01). There were no dislocations, aseptic loosening, or revisions. Our findings suggest that metal-on-metal cementless prostheses with large-diameter femoral heads in THA can produce satisfactory results with good durability, a low rate of dislocation and aseptic loosening, and a low incidence of revisions in the short term. The benefits of this technique for elderly patients, especially those with weak muscle power and reduced cognitive function, include avoidance of severe cement-injection complications and early functional recovery.


Topical treatment of cutaneous metastases of malignant melanoma using combined imiquimod and 5-fluorouracil.
Despite multiple available options, the treatment of cutaneous melanoma metastases is often unsuccessful. Based on the hypothesis that imiquimod and 5-fluorouracil have synergistic antitumor properties, we used this topical combination to treat several patients. Our objective was to investigate the treatment combination in a small cohort of patients with surgically non-resectable melanoma metastases. The lesions of 5 patients with multiple cutaneous metastases were treated topically, 5 days per week, with 5-fluorouracil in the morning and imiquimod at night. 45 lesions were treated. A clinical response was seen in 44 lesions, with a complete response in 19 lesions and a partial response in 25. Stable disease was confirmed in the 1 remaining lesion. No patients developed new lesions during treatment. However, one patient had a recurrence 6 months after treatment discontinuation, followed by a partial response when rechallenged. The imiquimod and 5-fluorouracil combination is effective. That patients did not develop new, distant lesions suggests the achievement of locoregional control, probably by the induction of antitumor immune response.


I-Shaped Dimers of a Plant Chloroplast FOF1-ATP Synthase in Response to Changes in Ionic Strength.
F-type ATP synthases play a key role in oxidative and photophosphorylation processes generating adenosine triphosphate (ATP) for most biochemical reactions in living organisms. In contrast to the mitochondrial FOF1-ATP synthases, those of chloroplasts are known to be mostly monomers with approx. 15% fraction of oligomers interacting presumably non-specifically in a thylakoid membrane. To shed light on the nature of this difference we studied interactions of the chloroplast ATP synthases using small-angle X-ray scattering (SAXS) method. Here, we report evidence of I-shaped dimerization of solubilized FOF1-ATP synthases from spinach chloroplasts at different ionic strengths. The structural data were obtained by SAXS and demonstrated dimerization in response to ionic strength. The best model describing SAXS data was two ATP-synthases connected through F1/F1' parts, presumably via their δ-subunits, forming "I" shape dimers. Such I-shaped dimers might possibly connect the neighboring lamellae in thylakoid stacks assuming that the FOF1 monomers comprising such dimers are embedded in parallel opposing stacked thylakoid membrane areas. If this type of dimerization exists in nature, it might be one of the pathways of inhibition of chloroplast FOF1-ATP synthase for preventing ATP hydrolysis in the dark, when ionic strength in plant chloroplasts is rising. Together with a redox switch inserted into a γ-subunit of chloroplast FOF1 and lateral oligomerization, an I-shaped dimerization might comprise a subtle regulatory process of ATP synthesis and stabilize the structure of thylakoid stacks in chloroplasts.


Organismal complexity, cell differentiation and gene expression: human over mouse.
We present a molecular and cellular phenomenon underlying the intriguing increase in phenotypic organizational complexity. For the same set of human-mouse orthologous genes (11 534 gene pairs) and homologous tissues (32 tissue pairs), human shows a greater fraction of tissue-specific genes and a greater ratio of the total expression of tissue-specific genes to housekeeping genes in each studied tissue, which suggests a generally higher level of evolutionary cell differentiation (specialization). This phenomenon is spectacularly more pronounced in those human tissues that are more directly involved in the increase of complexity, longevity and body size (i.e. it is reflected on the organismal level as well). Genes with a change in expression breadth show a greater human-mouse divergence of promoter regions and encoded proteins (i.e. the functional genomics data are supported by the structural analysis). Human also shows the higher expression of translation machinery. The upstream untranslated regions (5'UTRs) of human mRNAs are longer than mouse 5'UTRs (even after correction for the difference in genome sizes) and contain more uAUG codons, which suggest a more complex regulation at the translational level in human cells (and agrees well with the augmented cell specialization).


Frequency of cardiac arrhythmias in horses during straight and untethered swimming.
Cardiac arrhythmias have not been previously reported in horses while swimming. To describe the type and frequency of encountered arrhythmias during repetitive swimming cycles. Descriptive observational study. Sixteen horses swam five pool lengths (75 m), each separated by an active recovery walk. Continuous electrocardiograms (ECGs) were recorded (n = 80) and analysed during the pre-swim, swim and active-recovery periods. Arrhythmias were categorised as sinus arrhythmia (SA), sinus block, sinus pause (compensatory and non-compensatory), second degree atrioventricular block (2AVB) for physiological arrhythmias, supraventricular premature depolarisation (SVPD) and ventricular premature depolarisation (VPD) for non-physiological arrhythmias. A linear mixed-effects model was used to examine the effects of repetitive swim lengths on arrhythmias and swimming parameters. Data were reported as median [interquartile range]. Fifteen horses (94%) experienced at least one arrhythmia; however, the frequency remained low and 2AVB were only observed during the pre-swim period. The swimming heart rate (HR) was 162 bpm [141;173]. Sinus blocks, sinus pauses, SA, SVPD and VPD were all recorded at least once during swimming. Except for one VPD couplet, all premature depolarisations were isolated. During active-recovery, the HR was 105 bpm [103;106], with SA observed in 13 horses (81%), isolated SVPD in six horses (38%), sinus pause in one horse (6%) but no VPD present. Limited number of horses precluding population prevalence assessment. High-quality underwater ECGs were acquired in swimming horses for the first time. The frequency of arrhythmias remained low and rare pathological arrhythmias were observed during repetitive swimming and active-recovery cycles. Swimming with active-recovery periods is not a high-risk cardio-arrhythmic exercise.


Interest of vestibular evaluation in sequentially implanted children: Preliminary results.
An early acquired or congenital absence of sensory input of the vestibule will lead to severe delayed posturomotor milestones. Previous studies have proven modifications and even complete ipsilateral loss of vestibular function after unilateral cochlear implantation. The objective of this study was to evaluate whether sequential cochlear implantation has an impact on vestibular function. Retrospective study from January 2012 to January 2015 including 26 patients. The first stage consisted of determining the vestibular status of 26 hearing impaired children who were candidates for a second cochlear implant. Three months after contralateral implantation, we reevaluated the vestibular function of the same patients. The vestibular evaluation consisted of multiple tests for canal and otolith function. A complete clinical vestibular evaluation was performed, including the head thrust test. This was followed by an instrumental assessment composed of the classic bicaloric test and vestibular evoked myogenic potentials testing with tone bursts. A high prevalence of vestibular dysfunction (69%) was found in our group of unilaterally implanted children. Three patients had a unique functional vestibule at the not yet implanted ear. Vestibular evoked myogenic potentials responses stayed present in 15 of the 19 patients with a VEMP-response before contralateral implantation. Results of the caloric test changed for 6 patients after contralateral implantation. After contralateral implantation, 37% of our patients manifested modifications of their vestibular status. Intrasubject comparison of bicaloric and vestibular evoked myogenic potentials testing before and after contralateral cochlear implantation showed that canal function was better preserved than saccular function. Seeing the high prevalence of vestibular dysfunction in our test group of unilateral implanted children, sequential implantation must be preceded by a vestibular assessment to prevent complete bilateral vestibular areflexia and its potential consequences. Presence of hyporeflexia at the yet-to-be implanted ear seems to be a situation particularly at risk.


The effect of different combinations of local anaesthesia, sedative and non-steroidal anti-inflammatory drugs on daily growth rates of dairy calves after disbudding.
To assess the effect of sedation and local anaesthesia (LA) at disbudding, and the addition of meloxicam or ketoprofen treatment, on weight gain in dairy calves following disbudding. Friesian-Jersey cross calves, from four dairy farms, were enrolled when 3-6 weeks old. All calves (n=271) were disbudded by veterinary personnel and randomly assigned to six groups: 136 were disbudded without sedation or LA, of which 31 received 20 mg meloxicam S/C and 75 received 150 mg ketoprofen I/M. A further 135 were disbudded with sedation (0.25 mg/kg xylazine I/M) and LA, of which 30 also received meloxicam and 75 received ketoprofen. Calves were weighed 3 days before, and 15 and 30 days after, disbudding (Day 0). Daily weight gain was analysed using mixed models and ANOVA. Complete results were obtained from 263 calves. From Day -3 to Day 15, the growth rate of calves disbudded without pain relief (0.53 (95% CI=0.47-0.60) kg/day) was less that of calves disbudded with some form of pain relief (0.65 (95% CI=0.62-0.68) kg/d; p=0.004). There was no difference between the effect of meloxicam or ketoprofen (p=1.00). An interaction between use of sedation and LA and additional non-steroidal anti-inflammatory drugs (NSAID) meant that NSAID treatment did not increase growth rates in calves disbudded with sedation and LA but did increase growth rates for calves disbudded without pain relief (p<0.05). From Day 16 to Day 30 there was no effect of NSAID treatment on growth rate, but calves receiving LA and sedation grew faster (0.74 (95% CI=0.69-0.80) kg/day) than calves disbudded without LA and sedation (0.66 (95% CI=0.61-0.71) kg/day; p=0.018). From Day -3 to Day 30, calves disbudded with sedation and LA grew faster (0.71 (95%CI=0.64-0.77) kg/day) than calves disbudded without sedation and LA (0.60 (95% CI=0.55-0.65) kg/day; p=0.011). However, addition of NSAID to sedation and LA made no further difference to growth rates (p=0.69). Dairy calves disbudded with no pain relief had slower growth rates than calves receiving pain relief. From Day 15 to 30 calves given no pain relief, or NSAID alone, grew more slowly than those receiving sedation and LA at disbudding. The addition of NSAID treatment to sedation and LA did not further increase growth rates. This study adds to the evidence that pain management when disbudding is beneficial for calf productivity as well as calf welfare.


DETECTION OF NONEXUDATIVE CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
To evaluate eyes with age-related macular degeneration and high-risk characteristics for choroidal neovascularization (CNV) with optical coherence tomographic (OCT) angiography to determine whether earlier detection of CNV is possible. Eyes with drusen, pigmentary changes, and with CNV in the fellow eye were scanned with a 70-kHz spectral domain OCT system (Optovue RTVue-XR Avanti). The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to distinguish blood flow from static tissue. Two masked graders reviewed scans for CNV, defined as flow in the outer retinal/sub-RPE slab. Choroidal neovascularization flow area repeatability and between-grader reproducibility were calculated. Of 32 eyes, 2 (6%) were found to have Type 1 CNV with OCT angiography. The lesions were not associated with leakage on fluorescein angiography or fluid on OCT. One case was followed for 8 months without treatment, and the CNV flow area enlarged slightly without fluid buildup on OCT or vision loss. Between-grader reproducibility of the CNV flow area was 9.4% (coefficient of variation) and within-visit repeatability was 5.2% (pooled coefficient of variation). Optical coherence tomographic angiography can detect the presence of nonexudative CNV, lesions difficult to identify with fluorescein angiography and OCT. Further study is needed to understand the significance and natural history of these lesions.


An emerging infectious cause of renal impairment in the UK.
Hantaviruses are endemic in many central European countries, particularly the Balkans, infection causing non-specific 'flu-like symptoms and renal dysfunction which is self-limiting in the majority of cases. In this case, there was a diagnostic delay, resulting in numerous unnecessary investigations, prolonged hospital stay and almost an invasive renal biopsy. A travel history is therefore essential, to establish travel to an endemic region within the previous 2-6 weeks. With increasing travel and immigration, hantavirus is likely to be seen more frequently as an imported infection into the UK. However, further research is required to establish the potential for acquisition of infection here, as the animal host, the bank vole, is part of local wildlife. Therefore, the authors urge physicians to be alert to this possibility when faced with acute renal failure in association with an undiagnosed febrile illness, particularly when there is a history of an appropriate environmental or animal exposure.


Deep Latent Low-Rank Representation for Face Sketch Synthesis.
Face sketch synthesis is useful and profitable in digital entertainment. Most existing face sketch synthesis methods rely on the assumption that facial photographs/sketches form a low-dimensional manifold. Once the training data are insufficient, the manifold could not characterize the identity-specific information that is included in a test photograph but excluded in the training data. Thus, the synthesized sketch would lose this information, such as glasses, earrings, hairstyles, and hairpins. To provide the sufficient data and satisfy the assumption on manifold, we propose a novel face sketch synthesis framework based on deep latent low-rank representation (DLLRR) in this paper. The DLLRR induces the hidden training sketches with the identity-specific information as the hidden data to the insufficient original training sketches as the observed data. And it searches the lowest rank representation on the candidates of a test photograph from the both hidden and observed data. For the strong representational capability of the coupled autoencoder, we leverage it to reveal the hidden data. Experiment results on face photograph-sketch database illustrate that the proposed method can successfully provide the sufficient training data with the identity-specific information. And compared to the state of the arts, the proposed method synthesizes more clean and vivid face sketches.


The anti-inflammatory effect of opioids.
The anti-inflammatory activity of two novel opioids PM and PO as well as of pethidine was studied. The mouse paw edema, induced by various phlogistic agents, was significantly inhibited after the administration of opioids, fact that was independent of their antioxidant properties. The anti-inflammatory action of the above opioids was not reversed by naloxone. These results suggest that a variety of complex regulatory activities may be performed by opioid agonists via naloxone-sensitive or naloxone insensitive receptors on inflammatory cells, directly or indirectly by the inhibition of cytokines and mediators involved in inflammation.


Electron correlation effects in the adiabatic charge transfer reactions at the metal/polar liquid interface.
New simple expressions for average number of electrons in the valence orbital of a reacting ion and the charge susceptibility are obtained that allow one to calculate adiabatic free energy surfaces (AFES) and corresponding kinetic regime diagrams (KRD) for adiabatic processes of electron transfer from the ion, located in a polar liquid, to a metal within the framework of the exactly solvable (in the limit T-->0) model of the metal with the infinitely wide conduction band. This model represents one of limiting cases of the Anderson model that may be applied to s-p metals. Unlike previous studies of the adiabatic reactions in the model of the metal with the infinitely wide conduction band, the present work takes into account the electron-electron correlation effects in an exact manner. General results are illustrated with KRD which determine the regions of the physical parameters of the system corresponding to various types of electron transfer processes. AFES are calculated for some typical parameters sets. The exact AFES are compared with those calculated within the Hartree-Fock approximation. It is shown that the correlation effects are of importance and results not only in a considerable decrease of the activation free energy but also to qualitatively different shapes of AFES in some regions of the system parameters.


Interest and participation in support group programs among patients with colorectal cancer.
Previous studies have demonstrated that support intervention improved quality of life and survival for patients with breast, melanoma, prostate, and gastrointestinal cancer. A standardized approach to encourage participation in support group programs among patients with colorectal cancer (CRC) had been initiated at this study site. The purpose of this study was to examine the characteristics of patients with CRC interested in this type of intervention and to identify barriers to attendance at an established patient support program. Consecutive patients with CRC were informed and encouraged to attend Wellspring, a nonprofit patient support program that offers a wide range of services. A patient survey was conducted and correlated with data on the clinical, social, and demographic characteristics of patients. Factors predictive of interest in the Wellspring support program and barriers to attendance were examined.Fifty-eight patients were eligible for this study. A total of 44 (76%) surveys were completed. Predictors of interest in patient support were age less than 65 years, encouragement from medical staff to attend, level of education, comfort in spiritual beliefs, religious affiliation, and complementary/alternative medicine use. Disease stage, gender, ethnicity, and level of social supports were not significant in this population. Although patients were routinely informed about the program in a standardized fashion, a significant proportion (36.4%) of patients did not recall receiving encouragement. Multiple logistic regression showed that level of education and recollection of encouragement from medical staff were independent predictors of interest. Although 14 patients were interested in attending (32%), only 4 ultimately attended Wellspring programs (9.1%). The most frequently cited barrier to attendance was a perception of adequate support at home, followed by living too far away, no perceived need of supports, and not feeling well.A significant proportion of patients with CRC are interested in structured support programs, but only a minority of patients ultimately participate in such programs. Further participation may be achieved by recognizing common barriers to participation and optimizing strategies to enhance attendance. Optimizing use of support services such as Wellspring has the potential to improve the effectiveness of the multidisciplinary cancer care of patients with CRC.


Substituted Benzamides from Anti-inflammatory and p38 Kinase Inhibitors to Antitubercular Activity: Design, Synthesis and Screening.
Twenty one amide compounds possessing phenoxy/benzyloxy/pyridinyl groups have been synthesized by benzoylation of respective amines in presence of base with moderate to encouraging yields. Upon confirmation of structure, compounds were subjected for p38 kinase inhibitory, anti-inflammatory, antimicrobial and antitubercular activities. Anti-inflammatory activity was determined using carrageenan induced rat paw edema model while p38 kinase inhibitory activity was studied using ELISA method and serial dilution method was employed to determine MICs. Two compounds 4g and 4n showed over 30% p38 kinase inhibitory activity at 10 µM and best anti-inflammatory activity was found for compounds 4g, 4i, 4n and 4o which exhibited to reduce paw edema over 70%. Compound 4b was observed to be the most potent against gram +ve organisms with MIC value of 1.6 µG/mL and compound 4u displayed potent antibacterial activity against gram negative organisms. Most encouraging antitubercular activity was noticed for compounds 4u, 4r and 4k with 6.25, 12.5 and 12.5 µG/mL Further, in order to know the binding site interactions, a docking simulations of compounds was performed. These preliminary results will certainly show fruitful directions to improve the activities of compounds.


Quantifying the Effect of Temporomandibular Joint Intra-Articular Steroid Injection on Synovial Enhancement in Juvenile Idiopathic Arthritis.
To quantify the effect of intra-articular steroid injections (IASIs) on temporomandibular joint (TMJ) synovitis in children with juvenile idiopathic arthritis (JIA) using gadolinium-enhanced magnetic resonance imaging (MRI). The present study was a retrospective study of children with JIA who had undergone TMJ IASIs at Boston Children's Hospital. The patients were included if they had undergone contrast-enhanced MRI both before and after IASI and if the pre-IASI MRI had demonstrated synovitis (enhancement ratio [ER] >1.55). Patients with TMJ pathology or pain unrelated to JIA or a history of facial trauma were excluded. The predictor variables were age, gender, JIA subtype, exposure to medications for arthritis, and a family history of autoimmune disease. The primary outcome variable was the ER. Additional outcome variables included patient-reported pain and the maximal incisal opening (MIO). Twenty-nine subjects (83% female) with a total of 50 injected TMJs were included. The average age at JIA diagnosis and at IASI was 6.8 ± 1.7 years and 12.1 ± 1.9 years, respectively. The mean follow-up period was 22.9 ± 4.3 months (range 5 to 48). The ER decreased in all injected joints, with a mean reduction of 1.05 ± 1.01 (P < .001). The post-IASI ER was less than the normal threshold (1.55) in 18% of the injected TMJs. IASI was associated with an elimination of pain in 89% of the subjects (P < .001) and in augmentation of the MIO by 5.8 ± 2.6 mm (P < .001). In children with JIA and TMJ synovitis, TMJ IASI was associated with a reduction in synovial enhancement, decreased pain, and an increased MIO. Only 18% of injected joints, however, experienced complete resolution of synovitis. These results support the use of IASI in the management of the pain and dysfunction associated with TMJ synovitis. Further study is required to determine the efficacy of IASI in limiting inflammation and future joint destruction.


Stereometrical peculiriaties of energy-forming ultrastructures of pancreatic beta -cells under lipid loading during aging.
Chronic lipid loading in pancreatic beta -cells mitochondria of young and old animals causes the activation of ATP generation necessary for insulin secretion, activation of signalling system necessary for initiation of insulin secretion (the morphologic equivalents of which are revealed by elevation of volume share of mitochondrial matrix and increase of volume and number of crysts in the beta -cells), more prominent in old organisms. After loading with lipids in the certain term in young age mitochondrial processes are normalized (matrix turns back to initial volume, the crysts - to initial size and number), whereas in old age in comparison with the norm the activity of ATP-synthesis and signalling system are markedly impaired (significant decrease of matrix volume part and number of crysts, very marked elevation of volume part of aggregative-destructive sites, most important widening of intramembranous space); in some part of mitochondria complete energetic lack and blockage of signalling system take place (in some mitochondria the destructive-disorganization processes are markedly evident).


Efficacy of Thiamine in the Treatment of Postcardiac Arrest Patients: A Randomized Controlled Study.
Thiamine administration has been shown to improve survival in a postcardiac arrest animal study. We aimed to evaluate the efficacy of thiamine in comatose out-of-hospital cardiac arrest (OHCA) patients following return of spontaneous circulation. A randomized, double-blinded, placebo-controlled study was conducted. Thirty-seven OHCA patients were randomly assigned to receive either thiamine 100 mg every 8 hours or a placebo. The primary outcome was 28-day all-cause mortality. Over the course of 2 years, 37 patients were randomized to either receive thiamine (n = 20) or a placebo (n = 17). The primary outcome was not different between the groups: 10/20 (50%) in the thiamine group vs. 8/17 (47.1%) in the placebo group (P=0.93 by the log-rank test). There were no significant differences in secondary outcomes between the groups (good neurological outcome, lactate level, and S100B level). In this study, there were no significant differences in survival outcome. Further studies with a larger population are necessary to confirm these results.


Using tuberculosis patient characteristics to predict future cases with matching genotype results.
United States. It is unknown whether tuberculosis (TB) case or patient characteristics can predict the likelihood of future related TB cases. To estimate the likelihood for future related cases, i.e., cases with matching TB genotypes within the same county diagnosed within the 2 years following the year of reporting of each included case. We considered all TB cases with genotyping results reported in the United States during 2004-2010. Predictive scores were calculated based on patient characteristics by dividing the number of patients who were not the last case in a county-level TB genotype cluster by the total number of patients. Overall, there was a 30.8% chance that a future related case would be detected during the 2 years following the report year of any given case. Future related cases were detected in 34.7% of instances following the diagnosis of smear-positive cases, 51.9% of instances following the diagnosis of a homeless patient and 45.2% of instances following the diagnosis of a patient who reported substance abuse. Predictive scores ranged by race (White 13.9%, Native Hawaiian 43.8%) and age group (⩾65 years 13.1%, 0-4 years 43%), and were higher for US-born patients. Behavioral and sociodemographic factors can help predict the likelihood of future related cases and can be used to prioritize contact investigations.


Anesthesia Development in Mongolia: Strengthening Anesthesia Practice in Mongolia Through Education and Continuing Professional Development.
Anesthesia in Mongolia has undergone a period of major development over the past 17 years, thanks to the work of the Mongolian Society of Anesthesiologists (MSA) and the support of the World Federation of Societies of Anaesthesiologists and the Australian Society of Anaesthetists. The specialty has made major advances in training and in its standing among medical specialties in Mongolia. The MSA has produced members who are leaders in the development of anesthesia as well as emergency medicine and critical care. This has been achieved by engagement between the Ministry of Health and MSA, and with inexpensive but efficient programs to educate trainees and provide continuing professional development. There is now major work being done to achieve the Lancet Commission on Global Surgery goals of safe and accessible surgery for the population in a country that faces significant challenges of remote communities with vast distances.


Tryptophan transport in Neurospora crassa. II. Metabolic control.
The rate of tryptophan transport in Neurospora is regulated by the intracellular pool of tryptophan. When cells were shifted from growth in minimal medium to tryptophan-containing medium for 10 min, there was a 50% reduction in the rate of tryptophan transport. Intracellular tryptophan pools derived from indole were equally effective in reducing the rate of transport as externally supplied tryptophan. The regulatory influence of tryptophan on the transport system appears to be a property of all the amino acids transported by the tryptophan transport site or sites. Lysine and glutamic acid are not transported by the tryptophan transport site or sites and are ineffective in the regulation of tryptophan uptake. Continued protein synthesis is required for the maintenance of a functional tryptophan transport system. The half-life of the transport system, estimated by inhibiting protein synthesis with cycloheximide, was about 15 min. Turnover of the system occurred at 30 C but not at 4 C, suggesting that the breakdown of the system is enzymatically mediated. It was inferred that the rate of tryptophan transport in Neurospora is modulated through the maintenance of a delicate balance between the synthesis and breakdown of some component of the transport system.


[Study of the microwave fixation using the immunohistochemical method].
We evaluated microwave fixation of formalin immersed and microwave irradiated kidney and liver tissues by keratin immunostain using the paraffin embedded section. In the microwave irradiated tissues, the formalin fixed areas and the alcohol fixed areas were clearly detected because; 1) Alcohol fixed tissues are easily digested by pepsinization but formalin fixed tissues are not, and 2) Formalin fixed tissues revealed intense keratin staining after pepsinization, whereas intense keratin staining were noted in alcohol fixed tissues without preliminary pepsinization. The microwave irradiation fixed completely the tissues in about 20 sec. A thin, formalin-fixed layer was observed in the periphery of the tissues. A thin, alcohol-fixed layer was observed beneath the peripheral formalin fixed layer in some specimens. This area was thought to have been fixed during the dehydration of the paraffin blocks. However with microwave fixation, most of the central areas differed from those of the formalin or alcohol fixed areas. They showed sharp contrast on hematoxylin-eosin staining, conspicuous cellular membrane and only slight cellular shrinkage and swelling. Unlike the formalin and alcohol fixed tissues, the intensity of keratin staining was independent of preliminary pepsinization and keratin staining was observed. Therefore, the central areas were thought to be fixed by the microwave irradiation. This fixation method seems to be useful for immunostaining.