[Management of male urinary incontinence after radical prostatectomy (CTMH AFU 2006-2/5): place of perineal rehabilitation and medical treatment].
The treatment of incontinence is changing, but perineal rehabilitation still plays an essential role and is usually able to rapidly and effectively improve urinary incontinence. Medical treatment modalities are fairly limited: anticholinergic drugs have a limited efficacy except in the case of unstable bladder demonstrated by urodynamic assessment and, despite encouraging preliminary results, duloxetine has not obtained scientific recognition or marketing authorization.


Prothrombotic gene polymorphisms and plasma factors in young North Indian survivors of acute myocardial infarction.
The aim of this study was to evaluate the association of prothrombotic gene polymorphisms [factor V Leiden (FVL) 1691GA, factor VII (FVII) 10976GA, FVII HVR4, platelet membrane glycoproteins GP1BA 1018CT, GP1BA VNTR, integrin ITGB3 1565TC, integrin ITGA2 807CT and methylenetetrahydrofolate reductase (MTHFR) 677C/T], plasma factors (fibrinogen and homocysteine) and traditional risk factors with acute myocardial infarction (AMI) in 184 patients ≤ 40 years of age and 350 controls (≤ 40 years) from north India. Multiple logistic-regression analysis showed that hypertension (OR 1.9, 95 % CI 1.1-3.8, p = 0.042), diabetes mellitus (OR 10.5, 95 % CI 2.0-56.7, p = 0.006), smoking (OR 7.1, 95 % CI 3.7-13.6, p < 0.001), low socio-economic status (OR 13.5, 95 % CI 2.3-78.4, p = 0.004), high waist-hip ratio (OR 35.6, 95 % CI 11.1-53.7, p < 0.001) and FVL 1691GA (OR 6.0, 95 % CI 1.2-13.4, p = 0.03) were independent risk predictors of AMI in young. Elevated plasma fibrinogen also showed association with increased AMI risk. ITGA2 807C/T polymorphism showed protection against AMI in univariate analysis only, while GP1BA VNTR-ac (OR 0.4, 95 % CI 0.2-0.9, p = 0.033) showed significant protection even after adjusting for age and sex. Multinominal logistic-regression analysis showed gene-gene (GP1BA 1018C/T with GP1BA VNTR and ITGA2 807C/T with ITGB3 1565T/C polymorphisms) and gene-environment interactions (gene polymorphisms with smoking) operating in the occurrence of AMI in young. In conclusion, the role of inherited predisposition to thrombosis in complex, polygenic and multifactorial disease like AMI is limited to certain genetic factors, in combination with environmental factor like smoking.


A Non-competitive Serpin-Like Thrombin Inhibitor Isolated from Moringa oleifera Exhibit a High Affinity for Thrombin.
The majority of the clotting factors involved in blood coagulation pathways are serine proteases and thrombin is one of the key serine proteases involved in blood clotting. Many synthetic and chemical drugs targeting these proteases as therapeutics are known. However, they are associated with serious side effects such as bleeding, haemorrhage, edema etc. Serine protease inhibitors from plants have been suggested as one of the potential anticoagulant molecules against thrombosis. In the present work, a direct thrombin inhibitor from Moringa oleifera was isolated, purified and characterized. The homogeneity of the inhibitor is confirmed on native- PAGE. The purified inhibitor (5 µg) showed 63% thrombin inhibition at pH 7.2 at 37 °C. The IC50 value of the isolated inhibitor was determined as 4.23 µg. The inhibitor on SDS-PAGE appeared as a single protein-stained band corresponding to 50 kDa thereby indicating its molecular weight as 50 kDa. Purified thrombin inhibitor (5 µg) showed 12% inhibition of trypsin, and 17% inhibition of chymotrypsin. This suggests more specificity of purified inhibitor towards thrombin. The isolated inhibitor showed a non-competitive mode of inhibition against thrombin as determined by the Dixon plot. The inhibition constant (Ki) was calculated as 4.35 × 10-7 M. The present work reports for the first time a direct thrombin inhibitor from M. oleifera which may be further explored as an antithrombotic drug.


Isolation and genetical and biochemical characterization of mutants resistant to the alkaloid lycorine.
Mutants resistant to 200 micrograms/ml of the alkaloid lycorine (LYCR) in non-fermentable substrate were isolated after nitrosoguanidine mutagenesis. Tetrad analysis and growth of heterozygous (LYCR/lycS) diploids from two different mutants revealed that a single nuclear and dominant mutation is responsible for the resistant phenotype. In the wild type total protein synthesis is only slightly inhibited, whereas DNA and RNA synthesis is lowered to about 30% of the control. In the lycorine resistant mutants all macromolecular syntheses are unaffected by the drug.


Immuno-identification of cultures of fungi pathogenic to man.
Because isolates of the fungal pathogensBlastomyces dermatitidis. Coccidioides immitis, Histoplasma capsulatum, andParacoccidioides brasiliensis frequently vary widely in gross and microscopic features and are often difficult or impossible to convert to their tissue forms, a simple diagnostic procedure not dependent upon sporulation is needed to identify them specifically and rapidly. The exoantigen technique has been found to meet this need effectively. On the basis of studies with 166Histoplasma spp. isolates, 128C. immitis isolates, 59B. dermatitidis isolates, 30P. brasiliensis isolates, and 181 saprophytes, we determined that the exoantigen test is valuable for the presumptive identification of the four fungal pathogens studied. All of the positive reactions have correlated with the cultural, histologic, or other available laboratory data, and we are unaware of any false positive or flase negative reactions.


The influence of NAT2 genotypes on the plasma concentration of isoniazid and acetylisoniazid in Chinese pulmonary tuberculosis patients.
Isoniazid (INH) is widely used in the therapy of tuberculosis. Poor metabolizer (PM) of the NAT2 is an important reason of inter-individual difference of the plasma INH concentration. We studied the relationship between NAT2 genotype and INH and its metabolite acetylisoniazid (AcINH) concentration in Chinese people. Forty-six tuberculosis patients were enrolled in the study. Each patient took 300 mg INH daily for at least 7 days. Two hours after the INH was given, the vein blood was drawn. NAT2 genotypes of patients were detected by a reverse dot blot (RDB) method. The plasma concentration of INH and AcINH was determined by a precolumn derivation HPLC method. In 46 patients, homozygous mutant (m/m), heterozygous mutant (m/wt) and homozygous wild-type (wt/wt) subjects were 7, 22 and 17, respectively. Plasma concentration of INH and AcINH were 12.74+/-10.51 and 12.49+/-9.61 micromol/l, respectively. There was no statistical difference among 3 genotypes. The ratios of AcINH and INH (R(A/I)) of 3 genotypes were 0.67+/-0.34, 0.88+/-0.40 and 1.69+/-0.66, respectively. The R(A/I) of m/m and m/wt group were significantly lower than wt/wt group (P<0.01). The results suggest that various NAT2 genotypes in Chinese tuberculosis patients have great impact on the metabolism capacity of NAT2. This finding maybe valuable in the rational use of relevant drugs.


Synthesis of novel tellurium containing analogues of choline and acetylcholine and their quantitation by pyrolysis-gas chromatography-mass spectrometry.
Methods for the synthesis and quantitation of the novel choline analogues, telluronium choline and acetyltelluronium choline, are described. An assay procedure utilizing pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) with cold trapping was developed with [2H4]telluronium choline and [2H4]acetyltelluronium choline as internal standards. The telluronium compounds were ion-pair extracted from tissue with dipicrylamine, washed with 2-butanone, and pyrolyzed prior to GC-MS analysis. The compounds were monitored using selected ion monitoring at m/z 232 and m/z 190 for acetyltelluronium and telluronium choline, respectively, and at m/z 236 and m/z 194 for the analogous deuterated internal standards. The assay was linear over a range of 20 pmol-20 nmol of compound taken through the assay.


Life as a GDP--down under.
At the end of 1987 a colleague and friend from New Zealand offered me the opportunity to work in a general dental practice in his beautiful country for six months. It seemed an ideal way to combine some travelling 'down under' with living and working in Auckland thus affording the chance to get to know the country and its people better.


Tryptophan-rich domains of Plasmodium falciparum SURFIN4.2 and Plasmodium vivax PvSTP2 interact with membrane skeleton of red blood cell.
Plasmodium falciparum dramatically alters the morphology and properties of the infected red blood cells (iRBCs). A large group of exported proteins participate in these parasite-host interactions occurring at the iRBC membrane skeleton. SURFIN4.2 is one of iRBC surface protein that belongs to surface-associated interspersed protein (SURFIN) family. Although the intracellular tryptophan-rich domain (WRD) was proposed to be important for the translocation of SURFINs from Maurer's clefts to iRBC surface, the molecular basis of this observation has yet to be defined. The WRDs of P. falciparum SURFIN proteins and their orthologous Plasmodium vivax subtelomeric transmembrane proteins (PvSTPs) show homology to the intracellular regions of PfEMP1 and Pf332, both of which are involved in RBC membrane skeleton interactions, and contribute to malaria pathology. Two transfected lines expressing recombinant SURFINs (NTC-GFP and NTC-4.2WRD2-GFP) of the 3D7 sequence were generated by transfection in P. falciparum. In vitro binding assays were performed by using recombinant WRDs of SURFIN4.2/PvSTP2 and inside-out vesicles (IOVs). The interactions between the recombinant WRDs of SURFIN4.2/PvSTP2 with actin and spectrin were evaluated by the actin spin down assay and an enzyme-linked immunosorbent assay based binding assays, respectively. The recombinant SURFINs (NTC-4.2WRD2-GFP), in which the second WRD from SURFIN4.2 was added back to NTC-GFP, show diffused pattern of fluorescence in the iRBC cytosol. Furthermore, WRDs of SURFIN4.2/PvSTP2 were found to directly interact with the IOVs of RBC, with binding affinities ranging from 0.26 to 0.68 μM, values that are comparable to other reported parasite proteins that bind to the RBC membrane skeleton. Further experiments revealed that the second WRD of SURFIN4.2 bound to F-actin (K d = 5.16 μM) and spectrin (K d = 0.51 μM). Because PfEMP1 and Pf332 also bind to actin and/or spectrin, the authors propose that the interaction between WRD and RBC membrane skeleton might be a common feature of WRD-containing proteins and may be important for the translocation of these proteins from Maurer's clefts to the iRBC surface. The findings suggest a conserved mechanism of host-parasite interactions and targeting this interaction may disrupt the iRBC surface exposure of Plasmodium virulence-related proteins.


Evaluation of DNA extraction methods to detect bacterial targets in aerosol samples.
DNA-based monitoring of pathogens in aerosol samples requires extraction methods that provide high recovery of DNA. To identify a suitable method, we evaluated six DNA extraction methods for recovery of target-specific DNA from samples with four bacterial agents at low abundance (<10,000 genome copies per detection assay). These methods differed in rigor of cell disruption, approach for DNA capture, and extent of DNA purification. The six methods varied 1000-fold in the recovery of DNA from spores or cells of surrogates of Bacillus anthracis, Yersinia pestis, Burkholderia pseudomallei, and Francisella tularensis, each at about 105 CFU per sample. A custom method using paramagnetic Dynabeads for DNA capture greatly outperformed the other five methods. The cDynabead method provided about 80% recovery of target-specific DNA. The cDynabead method and a filtration method were further evaluated for DNA recovery from bacterial agents spiked on filters (c.a. 105 CFU of each agent per filter quadrant) that were subsequently used to collect background outdoor air particulates for 24-h. The filtration method generally failed to recover detectable quantities of target DNA from the spiked filters, suggesting at least a 100-fold loss of target DNA during extraction, whereas the custom cDynabead method consistently yielded DNA sufficient for target detection.


Respiratory Viral Pathogens in Children Evaluated at Military Treatment Facilities in Oahu, Hawaii From 2014 to 2018: Seasonality and Climatic Factors.
Five-year retrospective analysis of respiratory viruses in children less than 18 years old at Tripler Army Medical Center and outlying clinics in Oahu. Respiratory syncytial virus and influenza A showed pronounced seasonality with peaks from September to December and December to March, respectively. Results provide a better understanding of the timing of viral preventive strategies in Oahu.


Melatonin attenuates polychlorinated biphenyls induced apoptosis in the neuronal cells of cerebral cortex and cerebellum of adult male rats--in vivo.
Polychlorinated biphenyls (PCBs) are widespread persistent environmental contaminants that display a complex spectrum of toxicological properties, including neurotoxicity. Studies have shown that PCBs increase oxidative stress in brain, leading to apoptosis. The progressive loss of neurons in cerebral cortex and cerebellum, leads to various neurodegenerative diseases. Hence the present study is designed to determine PCBs toxicity toward neuronal cells and whether it could be inhibited by potent antioxidant melatonin. Four groups of adult male Wistar rats were treated for 30 days with corn oil, PCBs, PCBs+Mel and Melatonin, respectively. After treatment period the rats were euthanized and the brain was dissected to isolate cerebral cortex and cerebellum. The neuronal cells alone were then separated from the isolated brain regions, to detect the mRNA levels of apoptotic and neurofilament gene, a neuronal specific marker. Our results suggests that PCBs induces apoptosis in neuronal cells which is subsided by the anti apoptotic effect of melatonin.


Pseudomonas M162 confers protection against rainbow trout fry syndrome by stimulating immunity.
To evaluate the antagonistic effect of Pseudomonas M162 against Flavobacterium psychrophilum. The antagonistic activity of M162 was tested in vivo and in vitro, and its mode of action examined by siderophore production and immunological responses of rainbow trout (Oncorhynchus mykiss) fry. Pseudomonas M162 inhibited the growth of Fl. psychrophilum in vitro and increased the resistance of the fish against the pathogen, resulting in a relative per cent survival (RPS) of 39·2%. However, the siderophores produced by M162 did not have an inhibitory effect on Fl. psychrophilum. In fish fed with M162, the probiotic colonized the gastrointestinal tract and stimulated peripheral blood leucocyte counts, serum lysozyme activity and total serum immunoglobulin levels after 3 weeks from the start of feeding. This study showed the potential of Pseudomonas M162 as a probiotic by reducing the mortalities that occurred during an experimental Fl. psychrophilum infection, resulting mainly through the immunostimulatory effects of the bacterium. Rainbow trout fry syndrome (RTFS) causes high mortalities during the early life stages of the fish's life cycle, partly because their adaptive immunity has not yet fully developed. Thus, immunomodulation by probiotics could be an effective prophylactic method against RTFS.


Approaches to implement safe by design in early product design through combining risk assessment and Life Cycle Assessment.
The Safe by Design (SbD) concept aims to ensure the production, use and disposal of materials and products safely. While there is a growing interest in the potential of SbD to support policy commitments, such as the EU Green Deal and the Circular Economy Action Plan in Europe, methodological approaches and practical guidelines on SbD are, however, largely missing. The combined use of Life Cycle Assessment (LCA) and Risk Assessment (RA) is considered suitable to operationalize SbD over the whole life-cycle of a product. Here, we explore the potential of the combined use of LCA and RA at Technological Readiness Level (TRL) 1-6. We perform a review of the literature presenting and/or developing approaches that combine LCA and RA at early stages of product design. We identify that basic early-on-evaluations of safety (e.g., apply lifecycle thinking to assess risk hotspots, avoid use of hazardous chemicals, minimize other environmental impacts from chemicals) are more common, while more complex assessments (e.g., ex-ante LCA, control banding, predictive (eco)toxicology) require specialized expertise. The application of these simplified approaches and guidelines aims to avoid some obvious sources of risks and impacts at early stages. Critical gaps need to be addressed for wider application of SbD, including more studies in the product design context, developing tools and databases containing collated information on risk, greater collaboration between RA/LCA researchers and companies, and policy discussion on the expansion from SbD to Safe and Sustainable by Design (SSbD).


Congenital nemaline myopathy: two patients with consanguineous parents, one with a progressive course.
Clinical, morphological and genetic data are presented on two unrelated children with congenital nemaline myopathy. In one of these, the weakness and hypotonia were progressive. The parents of both children were second cousins. These cases together with those already published suggest that the frequency of consanguineous marriages in parents of children with nemaline myopathy is increased. This is a further argument in favour of an autosomal recessive type of congenital nemaline myopathy in addition to the autosomal dominant variety.


Using a Clinical Surveillance System to Detect Drug-Associated Hypoglycemia in Nursing Home Residents.
To determine whether a clinical surveillance system could be used to detect drug-associated hypoglycemia events and determine their incidence in nursing home (NH) residents. Retrospective cohort. Four NHs in western Pennsylvania. Any resident of the four NHs who had a computer-generated alert detecting potential drug-associated hypoglycemia over a 6-month period were included. Descriptive statistics were used to summarize all variables, including the frequency and distribution of alert type according to glucose threshold. Analyses were conducted according to numbers of alerts and residents. The medications associated with the drug-associated hypoglycemia alerts were identified, and frequency of their inclusion in alerts was calculated. Additional calculations included time to drug-associated hypoglycemic event alert from date of admission and frequency of events associated with postacute, short-stay (≤35 days) admissions. Seven hundred seventy-two alerts involving 141 residents were detected. Ninety (63.8%) residents had a glucose level of 55 mg/dL or less, and 42 (29.8%) had a glucose level of 40 mg/dL or less. Insulin orders were associated with 762 (98.7%) alerts. Overall incidence of drug-associated hypoglycemia events was 9.5 per 1,000 resident-days. Hypoglycemia can be detected using a clinical surveillance system. This evaluation found a high incidence of drug-associated hypoglycemia in a general NH population. Future studies are needed to determine the potential benefits of use of a surveillance system in real-time detection and management of hypoglycemia in NHs.


Effect of aging on biliary lipid composition and bile acid metabolism in normal Chilean women.
Biliary lipid composition was determined in fasting gallbladder bile of 12 young and 12 elderly asymptomatic Chilean women with normal weights and recent, normal cholecystograms. The proportion of biliary cholesterol and the lithogenic index were significantly higher in elderly females. Moreover, supersaturated bile was present in 8.3% of the young and in 41.7% of the older women studied. Obesity enhances the saturation of bile in older females: lithogenic bile was found in 100% of 4 elderly, obese women with radiologically normal gallbladders. The bile acid pool and cholic acid metabolism were studied in 5 young and 4 older normal females. Both groups showed similar values of bile acid pool, cholic acid synthesis, and turnover. These results indicate that aging per se modifies the proportions of biliary lipids in Chilean women, and provide a partial explanation for the frequency of gallstones observed among them. The increment in the lithogenic index of gallbladder bile with age takes place without significant changes in bile acid metabolism, suggesting that the canalicular secretion of cholesterol increases with aging.


Sexuality and intimacy in older adults.
In most long-term care settings, staff members tend to view a resident's attempts at sexual expression as "problem" behavior. However, we are increasingly recognizing that interest in, and the right to, sexual expression exists throughout the life span and should be supported. Assisted living nurses need information and tools to adequately address residents' sexual health and to overcome the many barriers to intimacy in this population. This article briefly reviews age and illness-related changes in sexual function; describes the research regarding older adults' and their family's and caregivers' attitudes regarding sexuality and intimacy; discusses sexuality and residents with dementia; and reviews nursing assessment and educational interventions that support healthy sexuality among older adults.


On the Gompertzian growth in the fractal space-time.
An analytical approach to determination of time-dependent temporal fractal dimension b(t)(t) and scaling factor a(t)(t) for the Gompertzian growth in the fractal space-time is presented. The derived formulae take into account the proper boundary conditions and permit a calculation of the mean values b(t)(t) and a(t)(t) at any period of time. The formulae derived have been tested on experimental data obtained by Schrek for the Brown-Pearce rabbit's tumor growth. The results obtained confirm a possibility of successful mapping of the experimental Gompertz curve onto the fractal power-law scaling function y(t)=a(t)tb(t) and support a thesis that Gompertzian growth is a self-similar and allometric process of a holistic nature.


The development and use of a comprehensive test for evaluating decentralized medical education--the WAMI experience.
The development of a comprehensive examination at the end of the first year of medical school is discussed. The implications of the results for the evaluation of the WAMI Program in decentralized medical education are presented.


Effect of chronic acetaldehyde intoxication on ethanol tolerance and membrane fatty acids.
Recent studies have suggested that acetaldehyde participates directly in the pathogenesis of alcoholism. Its action has been attributed mainly to its physico-chemical properties. Results of direct intoxication of laboratory animals with acetaldehyde have been reported, but only for short periods of exposure and at high doses. These are probably not representative of the conditions found during alcohol intoxication. The pulmonary route of administration described here enables long term intoxication with acetaldehyde, at levels corresponding to values measured during chronic ethanol intoxication. Chronic administration of acetaldehyde during 3 weeks induced a metabolic tolerance to ethanol as tested by the sleeping time after a challenge dose of ethanol; behavioural tolerance (measured by blood alcohol levels on waking) was not observed. At the end of the intoxication, phospholipid fatty acids of erythrocyte and synaptosome membranes were also analysed. Small changes in levels of the shorter fatty acids were observed in the phosphatidyl-choline fraction. By comparison with the effects of ethanol on the same membrane preparations, only a small part of this effect can be attributed to acetaldehyde. The first metabolite of ethanol has, however, a sure effect on the pattern of fatty acid phospholipids.


In vitro effects of 2-methyl-3-propylbutane-1,4-diol purified from Alstonia boonei on erythrocyte membrane stabilization and mitochondrial membrane permeabilization.
A recent review on the ethnomedicinal, chemical, pharmacological, and toxicological properties of Alstonia boonei revealed the plant's potential in the treatment and management of a range of diseases. However, most of these pharmacological effects are only traceable to the crude form of the plant extract and not specific natural products. Phytochemical investigation of the methanol fraction of the methanol extract of the stem-bark of Alstonia boonei led to the isolation and identification of 2-methyl-3-propylbutane-1,4-diol. The structures were elucidated by the application of 1D-, and 2D-NMR spectroscopic analyses and by comparison with literature data. In this study, the membrane stabilizing activity, mitochondrial membrane permeability transition pore opening, cytochrome c release, mitochondrial ATPase activity, and prevention of mitochondrial lipid peroxidation activity of 2-methyl-3-propylbutane-1,4-diol (MPBD) isolated from A. boonei were determined. The results showed that MPBD significantly (p < .05) prevented peroxidation of mitochondrial membrane lipids and hemolysis using both the heat-induced and hypotonic solution-induced membrane stabilization assays. On the contrary, the compound caused large amplitude swelling of rat liver mitochondria in the absence of calcium, significant (p < .05) cytochrome c release and enhancement of mitochondrial ATPase activity in vitro. Our findings suggest that MPBD showed characteristic biological properties useful in modulating cell death.


Acupuncture relieves symptoms in chronic prostatitis/chronic pelvic pain syndrome: a randomized, sham-controlled trial.
There are multiple approaches to the management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); and lately the data suggesting the ability of acupuncture treatment to decrease pain, positively impact quality of life and potentially modulate inflammation has suggested it as a potential therapeutic option for men with CP/CPPS. We conducted this study to determine whether acupuncture is really an effective therapeutic modality for CP/CPPS in terms of >50% decrease in total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score from baseline compared with sham. One hundred patients with CP/CPPS (category III B) in an outpatient urology clinic were randomized to receive acupuncture at either seven acupoints bilaterally or sham points adjacent to these points. NIH-CPSI was completed by each patient before and 6, 8, 16, 24 weeks after the treatment. Mean values of total CPSI score and subscores after the treatment and on follow-up following the treatment were compared. Of the acupuncture participants, 92% were NIH-CPSI responders (>50% decrease in total NIH-CPSI score from baseline) compared with 48% of sham participants, 8 weeks after the end of the therapy. Both groups experienced significant decrease in CPSI subscores throughout the whole follow-up period; however, the decline remained significantly greater in the active acupuncture group as compared with the sham group. Our results show that the use of acupuncture in treatment of men with CP/CPPS symptoms resulted in a significant decrease in total NIH-CPSI scores.


Sentinel lymph node biopsy in breast cancer: a history and current clinical recommendations.
The advent of sentinel lymph node biopsy changed the way the surgical community treated breast cancer. It also reduced the post operative morbidity for millions of patients. Now that sentinel lymph node biopsy has become the mainstay of treatment, new clinical questions have arisen and continued research is being done to answer these questions. This report details a brief history of sentinel lymph node biopsy and how it was applied in the treatment a breast cancer. This report also includes a review of the current literature regarding unique clinical scenarios involving sentinel lymph node biopsy in breast cancer including the ACOSOG Z011 trial.


Diagnosis of enteric fever by inhibition assay using peroxidase-labelled monoclonal antibody and Salmonella typhi lipopolysaccharide.
An enzyme-linked immunoassay was developed for diagnosing enteric fever. The test measured the inhibition of binding between a labelled, monoclonal IgM antibody and the insolubilized antigen, Salmonella typhi lipopolysaccharide (LPS). Good discrimination was seen between 32 proven typhoid cases (88.0 +/- 4.4% inhibition) and non-typhoid cases. The latter consisted of 27 febrile patients bacteriologically and serologically (Widal test) found to be negative for typhoid (26.3 +/- 10.8% inhibition), 46 patients screened for syphilis (VDRL test) but found negative (31.2 +/- 13.3% inhibition), and 27 healthy blood donors (44.6 +/- 13.9% inhibition). The test also efficiently detected all 5 known typhoid carriers (90.6 +/- 3.4% inhibition). The antibody binds antigen 9 in the LPS; however, this reaction was inhibited by antibodies directed against both this antigen and an adjacent antigen, 12. Anti-12 antibodies presumably inhibit by steric hindrance and their importance in the test is discussed. Thus, the assay potentially detects (only) those systemic infections caused by salmonellae that possess antigen 9 or 12 (viz. S. typhi and S. paratyphi A).


Urinary calcium excretion and insulin resistance in patients with acromegaly.
Renal complications in acromegaly include glomerular hyperfiltration, insulin resistance, hypercalciuria and urolithiasis. The aim of this study was to investigate whether urinary calcium (U(Ca)) excretion is a direct consequence of growth hormone secretion or secondary to hyperfiltration and/or insulin resistance. We performed a cross-sectional study of 58 patients diagnosed with acromegaly. Demographic data were obtained, serum analysis was performed, including insulin-like growth factor (IGF)-1, and 24-h urine collection, to measure urinary protein excretion, U(Ca) and phosphate excretion, as well as fractional excretion of sodium and potassium. We also calculated the homeostasis model assessment of insulin resistance (HOMA-IR). Patients were predominantly male (60.3%), and their mean age was 45.9 ± 14 years. Hypercalciuria was present in 24% of patients. Patients with higher HOMA-IR had higher IGF-1 levels, a trend toward higher body mass index and higher U(Ca) excretion. In univariate analysis, U(Ca) excretion was associated with HOMA-IR (r = 0.472, P = 0.001), phosphaturia (r = 0.457, P = 0.001), IGF-1 (r = 0.398, P = 0.002) and creatinine clearance (r = 0.394, P = 0.001). HOMA-IR and phosphaturia were independently associated with U(Ca) excretion. No independent associations were found between phosphaturia and HOMA-IR or IGF-1. The present study revealed an association between hypercalciuria and insulin resistance in patients with acromegaly. Further studies are required to fully understand the pathogenesis of these abnormalities in patients with acromegaly.


Genome analysis of Acidiplasma sp. MBA-1, a polyextremophilic archaeon predominant in the microbial community of a bioleaching reactor.
Results of genome analysis of a member of the family Ferroplasmaceae, Acidiplasma sp. strain MBA-1, an extremely acidophilic, moderately thermophilic archaeon oxidizing ferrous iron under oxic conditions and utilizing organic compounds. This strain was previously shown to predominate in the community carrying out biooxidation of pyrite-arsenopyrite gold-bearing concentrate. The genome was sequenced using the Illumina HiSeq 2000 platform. A total of 2306800 pairwise reads were obtained, corresponding to 300-fold coverage. Assembly was carried out by three programs in parallel. The optimal assembly contained nine contigs, the genome size was 1747364 bp, and N50 was 446845 bp. Annotation of the genome revealed 1749 protein-encoding sequences, as well as 46 tRNA genes and one rRNA gene copy. The results of genome analysis confirmed the previous data on the physiology of this organism. The gene of sulfocyanin (TZ01_06185), a blue copper-containing protein playing the key role in the iron-oxidizing electron transport chain, was identified in the genome. The genes encoding sulfur oxidoreductase (TZ01_04750) and sulfateadenilyl transferase (TZ01_04545), the enzymes of sulfur oxidation, were also identified. The genes involved in the transport and catabolism of organic compounds and the genes of the 3-hydroxypropionate/4-hydroxybutyrate cycle were revealed. The genome of Acidiplasma sp. MBA-1 is the first genome of this genus deposited to a public database DDBJ/EMBL/GenBank (accession no. JYHS00000000) and is of interest for further investigation of Acidiplasma archaea.


Tumour suppressor retinoblastoma protein Rb: a transcriptional regulator.
Rb was the first tumour suppressor identified through human genetic studies. The most significant achievement after almost twenty years since its cloning is the revelation that Rb possesses functions of a transcription regulator. Rb serves as a transducer between the cell cycle machinery and promoter-specific transcription factors. In this capacity, Rb is best known as a repressor of the E2F/DP family of transcription factors, which regulate expression of genes involved in cell proliferation and survival. An equally important aspect of Rb as a transcription regulator is that Rb also activates certain differentiation transcription factors to promote cellular differentiation. The molecular mechanisms behind the repressive effects of Rb on E2Fs have come to light in significant details, while those relating to Rb activation of differentiation transcription factors are much less understood. Finally, it has become clear that there are other aspects to Rb function that are not immediately related to transcription regulation.


Protein Complex Assemblies in Epithelial Cell Polarity and Asymmetric Cell Division.
Asymmetric local concentration of protein complexes on distinct membrane regions is a fundamental property in numerous biological processes and is a hallmark of cell polarity. Evolutionarily conserved core polarity proteins form specific and dynamic networks to regulate the establishment and maintenance of cell polarity, as well as distinct polarity-driven cellular events. This review focuses on the molecular and structural basis governing regulated formation of several sets of core cell polarity regulatory complexes, as well as their functions in epithelial cell polarization and asymmetric cell division.


A completely automated fluorometric blood cyanide method: a specific assay incorporating dialysis and distillation.
Discrete blood samples can be assayed at a rate of 20/hr. By means of a double lumen catheter, venous or arterial blood can be monitored continuously.


Socioeconomic and Racial/Ethnic Disparities in Perception of Health Status and Literacy in Spine Oncological Patients: Insights from the All of Us Research Program.
A cross-sectional study was performed using the National Institutes of Health All of Us survey database. The aim of this study was to assess socioeconomic and racial disparities in the perception of personal health, health literacy, and healthcare access among spine oncology patients. Racial, ethnic, and socioeconomic disparities in health literacy and perception of health status have been described for many disease processes. However, few studies have assessed the prevalence of these disparities among spine oncology patients. Adult spine oncology patients, identified using ICD-9/10-CM codes, were categorized by race/ethnicity: White/Caucasian (WC), Black/African-American (BAA), and Non-White Hispanic (NWH). Demographics and socioeconomic status were assessed. Questionnaire responses regarding baseline health status, perception of health status, health literacy, and barriers to healthcare were compared. Of the 1,175 patients identified, 207 (17.6%) were BAA, 267 (22.7%) were NWH, and 701 (59.7%) were WC. Socioeconomic status varied among cohorts, with WC patients reporting higher levels of education ( P<0.001 ), annual income greater than $50K ( P<0.001 ), and home ownership ( P<0.001 ). BAA and NWH patients reported greater rates of 7-day "Severe fatigue" ( P<0.001 ) and "10/10 pain" ( P<0.001 ) and lower rates of "Completely" able to perform everyday activities ( P<0.001 ). WC patients had a higher response rate for "Excellent/Very Good" regarding their own general health ( P<0.001 ) and quality ( P<0.001 ). The WC cohort had a significantly higher proportion of patients responding "Never" when assessing difficulty understanding ( P<0.001 ) and needing assistance with health materials ( P<0.001 ). BAA and NWH were significantly less likely to report feeling "Extremely" confident with medical forms ( P<0.001 ). BAA and NWH had significantly higher response rates to feeling "Somewhat Worried" about healthcare costs ( P<0.001 ) and with delaying medical care given "Can't Afford Co-pay" ( P<0.001 ). We identified disparities in perception of health status, literacy, and access among spine oncology patients. 4.


Postoperative radiographs after open reduction and internal fixation of the mandible: are they useful?
Mandibular fractures are common in oral and maxillofacial departments in the UK. The aim of this study was to find out the national practice in preoperative and postoperative radiographic investigations for fractured mandibles and to audit their diagnostic capacity, including specificity and sensitivity to short-term complications. The audit took place over a 4-month period and involved 100 patients across the Northern region. Ninety percent of patients were reviewed up to discharge and five of these patients developed a short-term postoperative complication. The postoperative radiograph was diagnostic in only one of the five cases. Overall, postoperative radiographs had a sensitivity of 20% and a specificity of 5% in their ability to predict short-term postoperative complications.


Radioautographic study of the axonal transport of proteins into the sensory nerve endings of avian mechanoreceptors.
The axonal transport of proteins to the nerve endings of Herbst and Grandry sensory receptors has been investigated by electron-microscope radioautography. Soon after the injection of [3H]leucine into the trigeminal ganglia of young ducks, labeled proteins are conveyed along the suborbital sensory nerves to the sensory nerve endings at rates of at least 200-280 mm/day. Most of these rapidly transported proteins accumulate in areas containing vesicles of various kinds and along the axolemmal region. Later, the bulk of labeled proteins migrate along the axons at rates of about 15 mm/day and are distributed mainly to the mitochondria. A small portion of labeled material is transferred to the adjoining modified Schwann and specialized Grandry receptor cells. It is concluded that the transport of proteins from sensory ganglia to sensory nerve endings of mechanoreceptors is conveyed at fast and intermediate rates and is mainly used for the renewal of vesicles, axolemmal constituents and mitochondria.


Cannabis Abuse Is Increasing and Associated with Increased Emergency Department Utilization in Gastroenterology Patients.
The role of cannabinoids in gastrointestinal diseases is controversial and of great interest, yet their use in patients has not been critically examined. To determine the prevalence and effects of cannabis abuse on healthcare utilization, as measured by emergency department (ED) visits, in a large, tertiary gastroenterology practice. All patients seen in the gastroenterology clinic at a tertiary care center during a 27-year period (1986-2013) were included in our study to determine the overall prevalence of cannabis abuse. We matched cannabis abusers 1:2 with non-abusing controls to determine the effect of cannabis on ED utilization, our primary outcome. We used multivariate linear regression to adjust for confounders and define the independent effect of cannabis abuse on ED utilization. Our prevalence study cohort included 190,303 GI clinic patients with an overall cannabis abuse prevalence of 0.80 % (1520 patients). From 1986 to 2012, the prevalence of cannabis abuse in this clinic increased by 0.73 % (0.03 %/year) (p < 0.0001). From the 1520 cannabis abusers identified, 467 patients were randomly selected as cases and were matched to 934 controls. From this retrospective cohort, the median ED visits/year for cannabis abusers was 1.88 versus 0.89 for non-abusers (p < 0.0001). After multivariate adjustment, cannabis abuse was associated with a 1.47-fold increase (95 % CI 1.23-1.76, p < 0.0001) in median ED visits/year. Reported cannabis abuse in GI clinic patients is less prevalent than in the adult US population, but is increasing. Cannabis abuse among gastroenterology patients is associated with increased ED visits.


Nocturnal enuresis and sleep disordered breathing in primary school children: Potential implications.
The association between nocturnal enuresis (NE) and sleep disordered breathing (SDB) has been repeatedly reported, but has primarily been focused on clinical cohorts. The purpose of this study, was to assess whether SDB-related symptoms such as snoring and unrefreshing sleep in the morning are associated with NE in a large-scale community school-based survey. A cross-sectional assessment using a standard questionnaire was conducted on nearly 20 000 primary school children (5-12 years old) in Matsuyama, Japan. Associations between NE and the frequencies of snoring and unrefreshing sleep were evaluated using multivariate logistic and regression analyses. Multivariate adjusted odds ratios (95% confidence intervals) for enuresis were 1.21 (1.04 to 1.40) and 1.36 (1.07 to 1.73) in boys who snored 1 or 2 nights per week and ≥3 nights per week, respectively (P for trend <0.0001). Those for enuresis were 1.67 (1.41 to 1.99) and 1.96 (1.63 to 2.36) in boys who showed unrefreshing sleep 1 or 2 nights per week and ≥3 nights per week, respectively (P for trend <0.0001). Significant associations between NE and snoring frequency emerged among children who did not report unrefreshing sleep (P-trend for boys and girls were <0.0001 and <0.01, respectively), while significant associations between NE and frequency of unrefreshing sleep were detected among children who snored ≥1 nights per week (P for trend >0.1). The pathogenic mechanisms linking snoring and unrefreshing sleep to increased risk of NE are unknown. However, snoring, a surrogate reporter of SDB, is associated with increased urine production, while unrefreshing sleep may result from disrupted sleep facilitating increased sleep pressure and elevated arousal thresholds. Thus, both SDB and unrefreshing sleep are potential independent risk factors of NE in school age children.


Factors affecting the incidence of lymph node metastases in small cancers of the breast.
Six hundred twenty-six cases of breast cancer treated at the Mason Clinic during the period from January 1, 1977 to December 31, 1987 were retrospectively reviewed. The review included only tumors 2 cm or less in maximal diameter and sought to determine the degree of correlation between axillary lymph node metastases in each of the following: patient age, estrogen receptor status, tumor location, degree of histologic differentiation, and tumor size. Only tumor size correlated significantly with the incidence of axillary lymph node metastases (p = 0.000001). The degree of differentiation appeared to correlate with the incidence of lymph node involvement but was not statistically significant (p = 0.17). No other subset of the above factors could be identified in association with axillary lymph node metastases. Forty-five noninvasive tumors were encountered in this series; none were associated with axillary lymph node metastases. The findings of this review lend support to the importance of screening mammography in the detection of breast cancer.


Resistance to activated protein C (APCR) in children with acute lymphoblastic leukaemia--the need for a prospective multicentre study.
Activated protein C resistance (APCR), usually due to the Arg506-->Gln point mutation of the factor V gene, has emerged as the most important hereditary cause of venous thromboembolism. Using an aPTT based method in the presence of APC, together with a DNA technique based on the polymerase chain reaction, we investigated 65 leukaemic children and 65 age-matched healthy controls for the presence of this mutation. In both groups three children showed APCR. All six children showed the common factor V gene mutation, Arg506-->Gln. Although no child in the control group presented with thrombosis, all three children with acute lymphoblastic leukaemia had thromboembolic events. Whether the poor anticoagulant response to activated protein C in leukaemic children treated with prednisone, vincristine, daunorubicin and asparaginase affects the risk of thrombotic events requires a more extensive multicentre study.


Sensitivity of certain porcine and bovine mycoplasmas to antimicrobial agents in a liquid medium test compared to a disc assay.
The sensitivity of some porcine and bovine mycoplasmas to potent antimicrobial agents was examined. Minimal inhibitory concentration (MIC) values were estimated for M. hyosynoviae, M. hyopneumoniae, M. dispar and M. bovis against enrofloxacin, lincomycin, tetracycline, tiamulin and tylosin, in a liquid medium test and in a disc assay. All 6 examined strains of each species and the respective type strains were significantly inhibited. The greatest sensitivity was noted for tiamulin against strains of M. hyosynoviae with a final MIC50 broth value of 0.025 micrograms ml-1 and disc value of 0.03 microgram per disc. Enrofloxacin was found very potent against M. hyopneumoniae with a final MIC50 of 0.025 microgram ml-1 and 0.1 microgram per disc, and for M. dispar with 0.05 microgram ml-1 and 0.03 microgram per disc. Most disc assay estimates in micrograms per disc were similar to or moderately greater than corresponding final broth figures in microgram ml-1. It may be possible to convert observed disc assay values into representative final broth MIC values for use in the clinic.


Gamma probe guided surgery for osteoid osteoma: is there any additive value of quantitative bone scintigraphy?
The aim of this study is to evaluate the efficiency of gamma probe guided osteoid osteoma surgery and the applicability of quantitative analyses obtained from preoperative bone scan images. This study involved 12 osteoid osteoma patients who were treated with gamma probe guided surgery after preoperative bone scan. The calculated contrast ratios between nidus and adjacent healthy bone from preoperative bone scan and the calculated percentages of count reduction after resection of nidus during intraoperative gamma probe application were compared. Patients were followed up for any recurrence or complications. The mean contrast ratio between nidus and adjacent healthy bone calculated from preoperative bone scan was 43.6% (range 33-53%). Following the nidus excision, an average of 55.8% (range 28-73%) count reduction was estimated with gamma probe in the tumor area. There was no correlation between preoperative scintigraphic contrast ratio and intraoperative gamma probe count reduction ratio (r = 0.46, p = 0.13). Complete cure was achieved in 11 (92%) patients with single operation, during the postoperative follow up period. None of the patients had any major or minor complications during or after the surgery. Due to high clinical success and low complication rate in osteoid osteoma surgery, gamma probe application is an effective and safe method that should be used more extensively in daily practice.


Communication of pain intensity and unpleasantness through magnitude ratings: Influence of scale type, but not gender of the participant.
A critical aspect for most human pain research is the ability of participants to communicate their first-person, experiential perspective to a third-person observer. This communication is frequently accomplished via pain ratings. The scale type can influence the communication of pain experiences and can contribute to gender differences in pain. This study examined the role of gender on pain ratings using noxious and innocuous stimuli across two types of rating scales. Healthy participants (n = 46) underwent noxious heat, auditory and visual stimulation paradigms. Pain intensity and unpleasantness ratings were collected using the visual analogue scale (VAS) and numerical rating scale (NRS). To determine if one rating scale allows a better report of small differences between different stimulus intensities, the sensitivity to small differences was calculated. Significant effects for rating scale were found for all stimulus modalities (noxious heat, auditory and visual, p < 0.001) with higher intensity and unpleasantness ratings for the NRS compared to the VAS. Overall, no effects of gender or interactions with gender were found. No differences in rating scale and gender were detected for sensitivity to small differences between stimuli. These findings confirm differences in rating scale usage; however, the different usage might not contribute significantly to gender differences in pain. There are differences in the usage of rating scales in which ratings for auditory, visual and noxious somatosensory stimuli are higher with NRS compared to VAS. Choosing a rating scale for research or clinical use should take this different item functioning into account.


Morbidity and functional outcome after double dynamic graciloplasty for anorectal reconstruction.
After abdominoperineal resection (APR), anorectal reconstruction with dynamic graciloplasty has been proposed to avoid abdominal colostomy and improve quality of life. Graciloplasties involving one or two gracilis muscles with various configurations have been described. The aim of this study was to evaluate morbidity and functional results in a homogeneous series of patients undergoing double dynamic graciloplasty following APR for rectal cancer. : From May 1995 to May 1998, 15 patients (ten men and five women; mean age 54 (range 39-77) years) underwent anorectal reconstruction with double dynamic graciloplasty after APR for low rectal carcinoma. All patients had preoperative radiotherapy (45 Gy), 11 with concomitant chemotherapy, eight had intraoperative radiotherapy (15 Gy) and ten received adjuvant chemotherapy for 6 months. The surgical procedure was performed in three stages: APR with coloperineal anastomosis and double graciloplasty (double muscle wrap); implantation of the stimulator 2 months later; and ileostomy closure after a training period. There was no operative death. At a mean of 28 (range 3-48) months of follow-up, there was no local recurrence; two patients had lung metastases. Early and late morbidity occurred in 11 patients, mainly related to the neosphincter (12 of 16 complications). The main complication was stenosis of the neosphincter (n = 6), which developed with electrical stimulation. Of 12 patients available for functional outcome, seven were continent, two were incontinent and three had an abdominal colostomy (two for incontinence, one for sepsis). Compared with patients without stenosis, patients with neosphincter stenosis required major reoperations (four versus zero) and had a poor outcome (two of six versus five of six with a good result). The double dynamic graciloplasty is associated with a high risk of neosphincter stenosis, which may entail morbidity, reintervention and poor functional results. The stenosis is a heterogeneous feature of the neosphincter induced by asymmetrical traction of both gracilis muscles. It is suggested that single dynamic graciloplasty should be used for anorectal reconstruction after APR. Presented to the 101st congress of the Association Française de Chirurgie in Paris, France, October 1999, and to the European Council of Coloproctology in Munich, Germany, October-November 1999


Unitary delayed rectifier channels of rat hippocampal neurons: properties of block by external tetraethylammonium ions.
Patch-clamp recording was used to characterise a delayed rectifier potassium channel and the effects of external tetraethylammonium (TEA) in neurons isolated from the CA1 region of cultured neonatal rat hippocampus. A preliminary kinetic analysis is presented. Very low concentrations of TEA included in the patch pipette solution had two effects on unitary currents: first unitary currents were reduced in amplitude, with an associated increase in open channel noise, and second channel mean open time was reduced. The reduction in unitary amplitude was consistent with a single TEA molecule blocking the channel with a voltage-independent Kd of 53.4 microM. The blocking and unblocking rate constants, estimated using two independent methods, were approximately 350 mM-1 ms-1 and 20 ms-1, both rate constants being independent of voltage. Channels blocked in this way appeared able to close normally without first having to become unblocked. The reduction in mean channel open time was probably due to a second, kinetically slower blocking reaction with a much lower Kd, probably between 300 and 800 microM. The voltage-independent blocking rate constant of the slower block was at least 25 times slower than that of the faster block.


Asian management of hypertension: Current status, home blood pressure, and specific concerns in Indonesia.
Over one-third of the population in Indonesia has hypertension, almost two-thirds of treated patients have uncontrolled blood pressure (BP), and the majority of patients with hypertension also have comorbidities. Home BP monitoring (HBPM) is a useful tool for diagnosing and managing hypertension. The use of HBPM is recommended by the latest consensus from the Indonesian Society of Hypertension (2019), and nearly, all doctors recommend HBPM for hypertensive patients. However, the use of HBPM in Indonesia is limited by the cost of devices and a perception that these devices are unreliable. In addition, knowledge about proper procedures is lacking. Withdrawal of mercury sphygmomanometers from the end of 2018 is expected to encourage the use of digital sphygmomanometers and the implementation of HBPM. The most common antihypertensive agent used in Indonesia varies by patient age, being angiotensin-converting enzyme (ACE) inhibitors in those aged 40-60 years and calcium channel blockers (CCBs) in older patients. Across all age groups, combination therapy with a CCB plus an angiotensin receptor blocker was common (41%-42% of patients). The high prevalence of hypertension in Indonesia has an important economic impact, and approaches to increase awareness of the disease and adherence to therapy are needed, particularly given data showing the benefits of strict BP control.


Thrombosis of the cranial vena cava in a cow with bronchopneumonia and traumatic reticuloperitonitis.
This paper reports the clinical findings, surgical and medical management, and necropsy of a 6-year-old cow with thrombosis of the cranial vena cava and thrombo-embolic pneumonia following traumatic reticuloperitonitis. The clinical diagnosis was confirmed by necropsy.


Bilateral vs Unilateral Total Knee Arthroplasty: Racial Variation in Utilization and In-Hospital Major Complication Rates.
We sought to examine bilateral total knee arthroplasty (BTKA) vs unilateral TKA (UTKA) utilization and in-hospital complications comparing African Americans (AAs) and Whites. In this retrospective analysis of patients ≥50 years who underwent elective primary TKA, the (2007-2016) database of the Healthcare Cost and Utilization Project (National Inpatient Sample) was used. We computed differences in temporal trends in utilization and major in-hospital complication rates of BTKA vs UTKA comparing AAs and Whites. We performed multivariable logistic regression models to assess racial differences in trends adjusting for individual-, hospital- and community-level variables. Discharge weights were used to enable nationwide estimates. We used multiple imputation procedures to impute values for 12% missing race information. An estimated 276,194 BTKA and 5,528,429 UTKA were performed in the US. The proportion of BTKA among all TKAs declined, and AAs were significantly less likely to undergo BTKA compared to Whites throughout the study period (trend P = .01). In-hospital complication rates for UTKA were higher in AAs compared to Whites throughout the study period (trend P < .0001). However, for BTKA, the in-hospital complication rates varied between Whites and AAs throughout the study period (trend P = .09). In this nationwide sample of patients who underwent total knee arthroplasty from 2007 to 2016, the utilization of BTKA was higher in Whites compared to AAs. On the other hand, while AAs have consistently higher in-hospital complication rates in UTKA over the time period, this pattern was not consistent for BTKA.


[ECG studies during esophagogastroduodenoscopy].
Esophago-gastro-duodenoscopy combined with ECG-monitoring was carried out on a total of 300 patients. In the group of patients with pulmonary, cardiac and vascular damage (102 patients) there was a high incidence of irregularities in the rhythm and repolarization (21.2% and 36.2% resp.) The deviations observed were of a transitory nature and no permanent damage or deaths occurred.


Assessment of reliability and information quality of YouTube videos about root canal treatment after 2016.
This study aimed to assess and update the content, reliability, and information quality of content related to root canal treatment (RCTx) on YouTube and evaluate the correlation between each evaluation index. YouTube was searched using two terms related to RCTx ("root canal and endodontic treatment"). A total of 240 videos (120 for each search term) were screened. Exclusion criteria were as follows: no sound or visuals, non-English, irrelevant to the search term, longer than 15 min, duplicate, or old (uploaded before 2016). After exclusion, 50 videos of "root canal treatment" and 45 videos of "endodontic treatment" were analyzed. Video length, total number of views, likes, dislikes, comments, and days since upload were recorded using descriptive video data. Viewers' interaction, reliability and information quality of the video, and quality of video content were measured using nondescriptive video data. The interaction index and video power index were used for viewer interactions, and the modified DISCERN index, JAMA criteria, and Global Quality Score were used to assess the reliability and information quality of the video. The quality of the video content was measured using the completeness score. The videos of the "root canal treatment" group had a significantly higher completeness score for the etiology and symptoms (p < 0.05), and videos of the "endodontic treatment" group showed a higher interaction index, completeness score for the procedure (p < 0.05). Videos for dentists had significantly higher completeness scores for the procedure, while videos for laypersons had higher completeness scores for etiology, anatomy, symptoms, and prognosis (p < 0.05). Furthermore, the total completeness score and the interaction index of the videos for laypersons were significantly higher (p < 0.05). The videos uploaded by the university had a significantly higher modified DISCERN index (p = 0.044), and the JAMA score was significantly higher in the commercial group (p = 0.001). Although the accuracy of videos related to RCTx was higher in videos by universities and professionals, the total completeness of YouTube videos was low regardless of the video source. Therefore, professionals should be responsible for providing more accurate and reliable videos.


Physical activity attitudes among adolescents in Bangladesh.
The purpose of this study was to examine physical activity (PA) attitudes among adolescents in Bangladesh and their associations with sociodemographic, lifestyle and activity-related factors. Cross-sectional study. A total of 781 students (52% female; mean age 14.3 years, SD 1.1) from eight secondary schools in Dhaka, Bangladesh, completed a written questionnaire. Exploratory factor analysis was used to derive positive and negative PA attitude measures. Generalized estimating equations were used to examine the associations. The most frequent positive attitudes were PA would 'get or keep me in shape' (81%) and 'be fun' (73%). Common negative attitudes were PA 'would make me hot and sweaty' (51%) and 'is hard work' (42%). Multivariable analysis showed that positive PA attitudes were more likely among adolescents who had physical education classes, adolescents involved in school sports, adolescents who ate fresh fruit and vegetables daily, and adolescents who had breakfast regularly. Negative PA attitudes were more likely among girls, adolescents who slept ≤8 h/night, and adolescents who were overweight or obese; and were less common among adolescents who ate fresh fruit and vegetables daily. This study suggests that PA interventions for adolescents should highlight benefits for being in shape and having fun as key components of positive PA attitudes; and address negative attitudes of PA being hot and hard work. Specific strategies may be needed to address negative PA attitudes among girls, adolescents who are overweight or obese, and adolescents with insufficient sleep.


Burns prevention in Europe--a report of a study tour 1982.
As in burns treatment, certain countries in Western Europe have also been able to achieve a lot in the field of Burns Prevention. In order to learn about the methods of prevention adopted by these countries and their effectiveness, a short study tour was sponsored by the Burns Association of India and the Sir Dorabji Tata Trust.


Correlation between severity of temporomandibular disorder and mandibular range of motion.
The aim of the present study was to determine the association between the severity of temporomandibular disorder (TMD) and mandibular range of motion (ROM). For such, a cross-sectional study was carried out with a sample of 92 women from the university community. The Fonseca's anamnestic index (FAI) was used to determine the severity of TMD, as follows: without TMD (n = 23), mild TMD (n = 23), moderate TMD (n = 23), and severe TMD (n = 23). Mouth opening, lateral excursion and protrusion of the mandible were measured. Spearman's correlation coefficients were calculated to determine the association between the FAI and mandibular ROM. Comparisons among groups were performed using the Kruskal-Wallis test with Dunn's post hoc test. No significant associations were found between TMD severity based on the classification of the FAI and ROM of functional mouth opening (rs = -0.001, p = 0.987), maximum active mouth opening (rs = -0.023, p = 0.822), passive mouth opening (rs = -0.026, p = 0.803), left lateral excursion (rs = 0.125, p = 0.231), right lateral excursion (rs = 0.087, p = 0.406) or protrusion (rs = -0.148, p = 0.157). Moreover, no statistically significant differences among severity groups were found (p > 0.05). Based on the findings of the present study, the severity of signs and symptoms of TMD was not associated with mandibular range of motion.


Helodermin stimulates prolactin secretion in the rat.
The effect of helodermin, a member of the secretin/vasoactive intestinal polypeptide (VIP)/peptide histidine isoleucine (PHI) family of peptides, on pituitary prolactin (PRL) secretion was examined in the rat. Either i.c.v. or i.v. injection of helodermin resulted in a dose-related increase in plasma PRL levels in urethane-anesthetized male rats. At the doses tested the potency of helodermin to raise plasma PRL levels was greater than that of rat PHI and porcine PHI, and as great as that of VIP.


Increases of spinal kinin receptor binding sites in two rat models of insulin resistance.
An autoradiographic study was conducted to determine whether kinin receptors are altered in the rat spinal cord in two experimental models of chronic hyperglycemia and insulin resistance. Sprague-Dawley rats were given 10% d-glucose in their drinking water alone or with insulin (9 mU/kg/min with osmotic pumps) for 4 weeks. Both groups and control rats were treated either with a normal chow diet or with an alpha-lipoic acid-supplemented diet as antioxidant therapy. After 4 weeks of treatment, glycemia, insulinemia, blood pressure, insulin resistance index, the production of superoxide anion in the aorta and the density of B2 receptor binding sites in the dorsal horn were significantly increased in the two models. These effects were prevented or attenuated by alpha-lipoic acid. In contrast, B2 receptor binding sites of most spinal cord laminae were increased in the glucose group only and were not affected by alpha-lipoic acid. Results show that chronic hyperglycemia associated with insulin resistance increases B1 and B2 receptor binding sites in the rat spinal cord through distinct mechanisms, including the oxidative stress for the B1 receptor.


Characteristics and Health Risk Assessment of Semi-Volatile Organic Contaminants in Rural Pond Water of Hebei Province.
Pond water as surface water has certain environmental impacts on environmental media such as groundwater, lakes, atmosphere, and soil. Organic pollutants present in pond water may pose health risks to humans, but research on organic pollutants in pond water is rare. Here, taking pond water collected in rural areas of Hebei province as the sample, we analyzed and evaluated four categories of semi-volatile organic compounds (SVOCs), including 11 phenolic compounds, 7 aniline compounds, 16 parent polycyclic aromatic hydrocarbons (PAHs), 14 PAH derivatives, and 16 phthalate esters (PAEs). The results show that the 10 water samples contained 26.2-17034 ng/L of Σ phenols, 33.7-2612 ng/L of Σ anilines, 33.9-1651 ng/L of Σ PAHs, and 59.0-2800 ng/L of Σ PAEs. Furthermore, non-carcinogenic risk and carcinogenic risk caused by SVOCs through direct ingestion and dermal exposure were also assessed. The current levels of non-carcinogenic risks and carcinogenic risks through these two means of exposure are within acceptable limits, except for the site 1 and site 5 in Hebei province where a total cancer risk exceeds 10-6. It can be concluded that the pond water studied had a low risk of carcinogenicity to the human.


Quantifying substantial carcinogenesis of genetic and environmental factors from measurement error in the number of stem cell divisions.
The relative contributions of genetic and environmental factors versus unavoidable stochastic risk factors to the variation in cancer risk among tissues have become a widely-discussed topic. Some claim that the stochastic effects of DNA replication are mainly responsible, others believe that cancer risk is heavily affected by environmental and hereditary factors. Some of these studies made evidence from the correlation analysis between the lifetime number of stem cell divisions within each tissue and tissue-specific lifetime cancer risk. However, they did not consider the measurement error in the estimated number of stem cell divisions, which is caused by the exposure to different levels of genetic and environmental factors. This will obscure the authentic contribution of environmental or inherited factors. In this study, we proposed two distinct modeling strategies, which integrate the measurement error model with the prevailing model of carcinogenesis to quantitatively evaluate the contribution of hereditary and environmental factors to cancer development. Then, we applied the proposed strategies to cancer data from 423 registries in 68 different countries (global-wide), 125 registries across China (national-wide of China), and 139 counties in Shandong province (Shandong provincial, China), respectively. The results suggest that the contribution of genetic and environmental factors is at least 92% to the variation in cancer risk among 17 tissues. Moreover, mutations occurring in progenitor cells and differentiated cells are less likely to be accumulated enough for cancer to occur, and the carcinogenesis is more likely to originate from stem cells. Except for medulloblastoma, the contribution of genetic and environmental factors to the risk of other 16 organ-specific cancers are all more than 60%. This work provides additional evidence that genetic and environmental factors play leading roles in cancer development. Therefore, the identification of modifiable environmental and hereditary risk factors for each cancer is highly recommended, and primary prevention in early life-course should be the major focus of cancer prevention.


Groundwater contamination risk assessment using a modified DRATICL model and pollution loading: A case study in the Guanzhong Basin of China.
Groundwater contamination risk assessment is not only the basis for groundwater management, but also an effective tool for groundwater pollution control and prevention. However, only groundwater vulnerability assessment is not enough to prove the risk of groundwater contamination. Therefore, this study describes an evaluation method combining aquifer intrinsic vulnerability and pollution source loading to evaluate groundwater contamination risk in Guanzhong Basin on a macro scale. A modified DRATICL model was introduced to evaluate the intrinsic vulnerability, and the analytic hierarchy process (AHP) and the entropy weight method were combined to determine the weight of each evaluation factor. Pollution loading was evaluated by quantifying the characteristics of potential pollution sources, mainly including pollutant toxicity, pollutant release possibility and potential pollutant release amount. Finally, total iron, Cl-, SO42-, F-, COD (Chemical Oxygen Demand), NO3-, NO2- and TDS (Total Dissolved Solids) are used to calculate the water quality index and verify the model results. The results showed that industries were the most harmful potential pollution sources in the study area, followed by landfills. Very high vulnerability areas were mainly situated around Huazhou District, Huayin and Dali County, as well as the low terraces around Zhouzhi County and Hu County, which are mainly caused by shallow groundwater depth and high net recharge. The final groundwater contamination risk results showed the high groundwater contamination risks are detected around Xi'an City, Xianyang City, Hancheng City and Dali County. Both high vulnerability and high pollution loading were present at the Jingwei District in the north of Xi'an City, where a priority attention should be given.


The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone stimulates phagocytic activity in human macrophages through the p38 MAPK pathway.
Quorum-sensing is an important mechanism for the regulation of bacteria-to-bacteria communication. Recent advances have demonstrated that the Pseudomonas aeruginosa signaling molecule N-(3-oxododecanoyl)-L-homoserine lactone (3O-C(12)-HSL) is also a potent modulator of eukaryotic cells and may thus play an important role in the host response during P. aeruginosa infections. Little is known, however, about specific effects of 3O-C(12)-HSL molecules on human macrophages. To address this issue, we investigated the influence of 3O-C(12)-HSL on the phagocytic activity, production of reactive oxygen species, and activation of p38 and p42/44 MAPK signaling pathways in human macrophages. We show an effect of 3O-C(12)-HSL on the phagocytic capacity in human macrophages, which depends on concentration and time of exposure. When cells were exposed to 100 microM 3O-C(12)-HSL for 30 min or 1 h, the phagocytic activity increased 1.8 and 1.6 times, respectively. The 3O-C(12)-HSL treatments had no significant effect on the level of reactive oxygen species production. Furthermore, the p38 MAPK, but not the p42/44 MAPK, signaling pathway was activated in response to 3O-C(12)-HSL. In addition, specific blocking of p38 MAPK activation with 10 microM SB 203580 prevented the 3O-C(12)-HSL-induced increase in the phagocytic activity. These findings demonstrate that the bacterial quorum-sensing can play a significant role also in regulation of macrophage activity during infections caused by P. aeruginosa.


Role of actin filament organization in CFTR activation.
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion-selective channel whose dysfunction leads to the onset of cystic fibrosis. CFTR activation is normally elicited by stimulation of the cAMP pathway, which effects protein kinase A activation. However, previous studies from our laboratory indicate that the actin cytoskeleton is also required for a proper CFTR function. In this report, the regulatory role of actin filament organization in the activation of CFTR was explored. Maneuvers to modify the steady-state organization of actin filaments elicit the activation of CFTR in the absence of a functional cAMP pathway. Partial disruption of the actin cytoskeleton of CFTR-expressing cells with cytochalasin D (CD) induced CFTR activation in the absence of an activated PKA. Similar findings were obtained by intracellular dialysis with the actin-severing protein gelsolin. However, extended treatment with CD leading to the collapse of the actin cytoskeleton rendered CFTR completely insensitive to direct PKA activation. cAMP activation of CFTR was also found to be dysfunctional in cells lacking the actin-crosslinking protein ABP-280, which was recovered after dialysis of the cells with filamin, a homologue of ABP-280. The present data indicate that an organized actin network is required for the proper cAMP-dependent activation of CFTR. The possibility is also explored that actin must be directly associated with CFTR to elicit its activation, further suggesting that this channel protein may bind actin as well.


Periarticular injection of liposomal bupivacaine in total knee arthroplasty.
The purpose of this study was to determine whether the use of a periarticular injection using liposomal bupivacaine could decrease pain and improve outcomes after total knee arthroplasty. Fifty consecutive patients received no periarticular injections (group A). Another 50 consecutive patients received a periarticular injection of liposomal bupivacaine (group B). There were no differences in the groups with respect to gender, age, body mass index (BMI), or comorbidities. There was a significant reduction in the amount of narcotics used in the liposomal bupivacaine group (60.97-mg oral morphine equivalent vs 89.74 mg, P = 0.009). Patients in group B with a BMI <40 and a Charlson comorbidity index of 0-3 had decreased length of stay (2.64 vs 3.06 days, P = .004), narcotic use over 24-48 hours (110.66 vs 182.47 mg, P = .013), and narcotic use over 48-72 hours (49.61 vs. 112.65 mg, P = .004). In patients with a BMI <40 and comorbidity index of ≤3, periarticular injection using liposomal bupivacaine leads to earlier discharge along with decreased use of narcotics.


Pentraxin 3 values during normal pregnancy.
Pentraxin 3 (PTX3) is an inflammatory molecule that has been reported to be a promising early biomarker for subsequent preeclampsia. The levels of PTX3 vary during pregnancy and it is thus a need to establish reference intervals during normal pregnancy. Repeated blood samples were collected from 52 healthy pregnant females. The samples were divided according to collection time into the following groups: week 7-17, week 17-24, week 24-28, week 28-31, week 31-34, week 34-38, before delivery and after delivery. The samples were analyzed for PTX3 with a sandwich ELISA and the 2.5 and 97.5 percentiles for each sample period was calculated. There was a continuous increase of serum PTX3 as pregnancy progressed. The increase was most evident after week 31 with the highest levels just before delivery.


Mediastinitis and blood transfusion in cardiac surgery: a systematic review.
Mediastinitis, a serious complication after cardiac surgery, increases morbidity, mortality, and cost of care. Accumulating evidence implicates blood transfusions in the development of mediastinitis. We conducted a systematic review to evaluate the association between allogeneic blood transfusion and mediastinitis in adult cardiac surgery patients. After a search of Medline, PubMed, Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, and the Institute for Scientific Information's Web of Knowledge (1990-2010) for relevant studies, 7 (3 prospective cohort and 4 retrospective reviews) met our inclusion/exclusion criteria. Between 20% and 80.2% of patients received blood transfusions, with an incidence of mediastinitis ranging from 0.1% to 2.3%. Five studies demonstrated an independent association between red blood cell transfusion and mediastinitis. Two studies identified a dose-response relationship. The findings of this systematic review suggest that allogeneic red blood cell transfusions are associated with an increased risk of mediastinitis in patients undergoing cardiac surgery. Individual risks and benefits should be assessed in each patient before a red blood cell transfusion.


Serial cardiac troponin concentrations as marker of cardiac toxicity in children with status asthmaticus treated with intravenous terbutaline.
The study's objectives were to evaluate serial troponin concentrations as a marker of cardiac toxicity in children receiving intravenous terbutaline for status asthmaticus and to study if troponin concentrations are affected by severity of asthma and risk factors for severe asthma. This was a prospective observational study in 20 consecutive patients who were admitted to a tertiary care pediatric intensive care unit for status asthmaticus and received intravenous terbutaline. Cardiac troponin I (cTnI) concentrations were measured half an hour before the bolus of intravenous terbutaline, 4 hours after terbutaline, and then every 24 hours until discontinuation of the continuous terbutaline infusion. Ten patients had cTnI concentrations greater than 0.03 ng/mL. Maximum cTnI concentrations were recorded after the terbutaline bolus in 6 patients, during terbutaline infusion in 3 patients, and before terbutaline use in 1 patient. Three of these 10 (3/10) patients showed increased cTnI concentrations before the terbutaline bolus. One patient had a significant elevation in cTnI concentration (peak level of 3.79 ng/mL) with electrocardiogram (ECG) changes of myocardial injury that normalized upon discontinuation of terbutaline. All other patients with elevated cTnI concentrations had normal ECG findings. Elevated cTnI concentrations were observed in 50% of patients treated with intravenous terbutaline for status asthmaticus. Clinically significant cardiotoxicity was not observed except in 1 patient in whom the abnormal ECG findings normalized upon discontinuation of terbutaline. There was no statistically significant difference in asthma severity or in the risk factors for severe asthma in children with and without elevation of cTnI concentrations.


Tongue function is important for masticatory performance in the healthy elderly: a cross-sectional survey of community-dwelling elderly.
The aim of this study was to determine the influences of oral motor function such as tongue function and bite force on masticatory performance in the elderly. We randomly selected 245 subjects who has 28 natural teeth among community-dwelling elderly. We evaluated masticatory performance using a gummy jelly, and also measured bite force, tongue muscle force, and the speed of tongue movement. We found that reduced masticatory performance to be associated with decreased the speed of tongue movement and/or tongue muscle force, indicating that reduced oral motor function also influences masticatory performance. These results suggest that keeping oral motor function, as well as maintenance of occlusal support, to be important for maintaining masticatory function in the elderly.


[Glucocorticoids as an adjunct in peripheral regional anesthesia. Move to the "Holy Grail of perineural analgesia"?!].
The role of dexamethasone as an adjunct in peripheral nerve blockades is still unclear. This article reviews the actual knowledge and scientific evidence for dexamethasone as an adjunct in peripheral regional anesthesia. Moreover, it discusses the benefits of the systemic versus the perineural mode of application. Dexamethasone prolongs sensible as well as motor blockades in peripheral nerve blocks when applied intravenously or perineurally. Regarding potentially local neurotoxicity, published patient data are not sufficient for final conclusions. After reviewing the actual literature, the authors prefer a systemic application mode (intravenously) over a perineural route of administration of dexamethasone as an adjunct for peripheral nerve blocks. This is due to the better understanding of potential side effects of the drug when applied intravenously. Dexamethasone might be a useful drug adjunct to prolong peripheral single shot nerve blocks.


Bidirectional association between sleep quality or duration and aggressive behaviour in early adolescents: A cross-lagged longitudinal study.
Several cross-sectional studies have suggested a strongly positive link between sleep and aggressive behaviour; however, longitudinal studies reporting the relationship between sleep and aggressive behaviour are lacking. This study aimed to examine whether a bidirectional relationship exists between sleep quality or duration and aggressive behaviour in early adolescents. A total of 1579 early adolescents (60.9 % boys) from the Chinese Early Adolescents Cohort study were included in this study. Data on sleep quality, sleep duration and aggressive behaviour collected at two time points (September 2019 and September 2021) were used, and the bidirectional relationship between sleep quality or duration and aggressive behaviour was examined using a cross-lagged model. The results revealed a bidirectional relationship between low sleep quality and highly aggressive behaviour. A shorter sleep duration did not predict highly aggressive behaviour, whereas only highly aggressive behaviour predicted a shorter sleep duration. Sleep quality and aggressive behaviour were interrelated over time among adolescents. However, sleep duration did not predict aggressive behaviour, suggesting that sleep quality, instead of sleep duration, should be the primary target for managing aggressive behaviour.


Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer.
The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15-3, another member of the human mammary epithelial antigen family. Serum BCM was evaluated in 151 and CA 15-3 in 134 patients with breast cancer, in 30 normal controls, in 9 pregnant women, and in 13 cancer patients (non-breast). Neither the normal controls nor the pregnant women had BCM levels greater than 25 U/ml. In contrast, 87 of 115 patients (75%) with metastatic breast cancer had BCM levels greater than 25 U/ml. All control persons had CA 15-3 levels less than 25 U/ml, but 2 out of 9 pregnant women (22%) had levels greater than 25 U/ml. Seventy-four out of 97 patients (76%) with metastatic breast cancer had CA 15-3 levels greater than 25 U/ml. A statistically significant correlation was found between BCM and CA 15-3 in the breast cancer patient group (r = 0.883, p less than 0.001, n = 134) and in the normal control group (r = 0.743, p less than 0.001, n = 30). BCM and CA 15.3 both showed no correlation with CEA in breast cancer patients (r = 0.060, n = 81; and r = 0.146, n = 78, respectively). BCM had a range of sensitivity similar to that of the CA 15-3 RIA. Our results suggest that BCM may be a useful new marker for monitoring the clinical course of patients with breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)


Striatal patch compartment lesions alter methamphetamine-induced behavior and immediate early gene expression in the striatum, substantia nigra and frontal cortex.
Methamphetamine (METH) induces stereotypy, which is characterized as inflexible, repetitive behavior. Enhanced activation of the patch compartment of the striatum has been correlated with stereotypy, suggesting that stereotypy may be related to preferential activation of this region. However, the specific contribution of the patch compartment to METH-induced stereotypy is not clear. To elucidate the involvement of the patch compartment to the development of METH-induced stereotypy, we determined if destruction of this sub-region altered METH-induced behaviors. Animals were bilaterally infused in the striatum with the neurotoxin dermorphin-saporin (DERM-SAP; 17 ng/μl) to specifically ablate the neurons of the patch compartment. Eight days later, animals were treated with METH (7.5 mg/kg), placed in activity chambers, observed for 2 h and killed. DERM-SAP pretreatment significantly reduced the number and total area of mu-labeled patches in the striatum. DERM-SAP pretreatment significantly reduced the intensity of METH-induced stereotypy and the spatial immobility typically observed with METH-induced stereotypy. In support of this observation, DERM-SAP pretreatment also significantly increased locomotor activity in METH-treated animals. In the striatum, DERM-SAP pretreatment attenuated METH-induced c-Fos expression in the patch compartment, while enhancing METH-induced c-Fos expression in the matrix compartment. DERM-SAP pretreatment followed by METH administration augmented c-Fos expression in the SNpc and reduced METH-induced c-Fos expression in the SNpr. In the medial prefrontal, but not sensorimotor cortex, c-Fos and zif/268 expression was increased following METH treatment in animals pre-treated with DERM-SAP. These data indicate that the patch compartment is necessary for the expression of repetitive behaviors and suggests that alterations in activity in the basal ganglia may contribute to this phenomenon.


Affinity labeling of dihydrofolate reductase with an antifolate glyoxal.
Dihydrofolate reductases from different species contain several highly conserved arginines, some of which have been shown by x-ray crystallography to have their guanido groups near the p-aminobenzoyl glutamate moiety of enzyme-bound methotrexate. The orientation of one of these (Arg-52) appears to be completely reversed in comparing the crystal structures of Escherichia coli with Lactobacillus casei enzyme (Bolin, J. T., Filman, D. J., Matthews, D. A., Hamlin, R. C., and Kraut, J. (1982). J. Biol. Chem. 257, 13650-13662). We synthesized a novel antifolate containing a glyoxal group designed to react specifically with active-site guanido groups which are able to approach the p-aminobenzoyl carbonyl of methotrexate. The binding of this compound to the enzyme was competitive with dihydrofolate (DHF) in ordinary buffers. In borate buffer at pH 8.0 it inactivated dihydrofolate reductases from both E. coli and L. casei at similar maximum rates, while the chicken liver enzyme was more slowly inactivated. The inactivation was stoichiometric, paralleled the loss of the glyoxal chromophore, and showed saturation kinetics. Inhibitor binding and thus inactivation was enhanced by NADPH, while DHF protected the enzyme. This allowed calculation of the Kd for DHF which was found to be identical with its Km. The stoichiometrically inactivated enzyme displayed the 340-nm chromophore characteristic of 4-aminopteridines bound to dihydrofolate reductase confirming active-site labeling with normal orientation of the ligand. The ligand remained covalently bound to inactivated enzyme upon denaturation at low pH but dissociated at neutral pH. Computer graphic modeling of the crystal structures predicted reaction of Arg-31 but not Arg-52 in L. casei dihydrofolate reductase and of only Arg-52 in the E. coli enzyme. Purification of the CNBr fragments from the inactivated enzymes gave a single labeled peptide for each species. The particular peptide tagged in each case was unaffected by the presence of NADPH and was in excellent agreement with the crystallographic predictions.


Cathepsin-L ameliorates cardiac hypertrophy through activation of the autophagy-lysosomal dependent protein processing pathways.
Autophagy is critical in the maintenance of cellular protein quality control, the final step of which involves the fusion of autophagosomes with lysosomes. Cathepsin-L (CTSL) is a key member of the lysosomal protease family that is expressed in the murine and human heart, and it may play an important role in protein turnover. We hypothesized that CTSL is important in regulating protein processing in the heart, particularly under pathological stress. Phenylephrine-induced cardiac hypertrophy in vitro was more pronounced in CTSL-deficient neonatal cardiomyocytes than in in controls. This was accompanied by a significant accumulation of autophagosomes, increased levels of ubiquitin-conjugated protein, as well as impaired protein degradation and decreased cell viability. These effects were partially rescued with CTSL1 replacement via adeno-associated virus-mediated gene transfer. In the in vivo murine model of aortic banding (AB), a deficiency in CTSL markedly exacerbated cardiac hypertrophy, worsened cardiac function, and increased mortality. Ctsl(-/-) AB mice demonstrated significantly decreased lysosomal activity and increased sarcomere-associated protein aggregation. Homeostasis of the endoplasmic reticulum was also altered by CTSL deficiency, with increases in Bip and GRP94 proteins, accompanied by increased ubiquitin-proteasome system activity and higher levels of ubiquitinated proteins in response to AB. These changes ultimately led to a decrease in cellular ATP production, enhanced oxidative stress, and increased cellular apoptosis. Lysosomal CTSL attenuates cardiac hypertrophy and preserves cardiac function through facilitation of autophagy and proteasomal protein processing.


Effect of fixation and embedding on Raman spectroscopic analysis of bone tissue.
Raman spectroscopy provides valuable information on the physicochemical properties of hard tissues. While the technique can analyze tissues in their native state, analysis of fixed, embedded, and sectioned specimens may be necessary on certain occasions. The information on the effects of fixatives and embedding media on Raman spectral properties is limited. We examined the effect of ethanol and glycerol as fixatives and a variety of embedding media (Araldite, Eponate, Technovit, glycol methacrylate, polymethyl methacrylate, and LR white) on Raman spectral properties (mineralization, crystallinity, and carbonation) measured from the cortical bone of mouse humeri. Humeri were fixed in ethanol or glycerol, followed by embedding in one of the media. Nonfixed, freeze-dried, and fixed but not embedded sections were also examined. Periosteal, endosteal, and midosteal regions of the intracortical envelope were analyzed. Raman spectra of fixative solutions and embedding media were also recorded separately in order to examine the specifics of overlap between spectra. We found significant effects of fixation, embedding, and anatomical location on Raman spectral properties. The interference of ethanol with tissue seemed to be relatively less pronounced than that of glycerol. However, there was no single combination of fixation and embedding that left Raman spectral parameters unaltered. We conclude that careful selection of a fixation and embedding combination should be made based on the parameter of interest and the type of tissue. It may be necessary to process multiple samples from the tissue, each using a combination appropriate for the Raman parameter in question.


Neural plasticity and recovery of function.
Recovery of the function after stroke is a consequence of many factors including resolution of oedema and survival of the ischaemic penumbra. In addition there is a growing interest in the role of central nervous system (CNS) reorganization. Much of the evidence supporting this comes from animal models of focal brain injury, but non-invasive techniques such as functional magnetic resonance imaging, transcranial magnetic stimulation, electroencephalography and magnetoencephalography now allow the study of the working human brain. Using these techniques it is apparent that the motor system of the brain adapts to damage in a way that attempts to preserve motor function. This has been demonstrated after stroke, as part of the ageing process, and even after disruption of normal motor cortex with repetitive transcranial magnetic stimulation. The result of this reorganization is a new functional architecture, one which will vary from patient to patient depending on the anatomy of the damage, the biological age of the patient and lastly the chronicity of the lesion. The success of any given therapeutic intervention will depend on how well it interacts with this new functional architecture. Thus it is crucial that the study of novel therapeutic strategies for treating motor impairment after stroke take account of this. This review maps out the attempts to describe functionally relevant adaptive changes in the human brain following focal damage. A greater understanding of how these changes are related to the recovery process will allow not only the development of novel therapeutic techniques that are based on neurobiological principles and designed to minimize impairment in patients suffering from stroke, but also to target these therapies at the appropriate patients.


Vimentin phosphorylation by Cdc2 in Schwann cell controls axon growth via β1-integrin activation.
Although preconditioning injury on the peripheral nerve induces axonal regenerative capacity in neurons, it is not known whether similar lesion effects occur in glial cells. Here we demonstrate that Schwann cells are activated by peripheral nerve preinjury and primed to mediate axon regeneration. Cdc2, which was induced from Schwann cells after sciatic nerve injury, phosphorylated vimentin almost exclusively in the distal nerve area. Phospho-vimentin-positive Schwann cells showed increased migration activity and were in close contact with process outgrowth of co-cultured neurons. Vimentin phosphorylation by Cdc2 was involved in β1-integrin activation leading to FAK phoshorylation and associated with Erk1/2 activation in Schwann cells. Neurite outgrowth of dorsal root ganglion neurons was increased by co-culture with activated Schwann cells, in which phospho-vimentin signaling was transmitted into β1-integrin activation. Then neurite outgrowth was suppressed by genetic depletion of phospho-vimentin and β1 integrin as well as inhibition of vimentin phosphorylation by Cdc2 inhibitor purvalanol A. The sciatic nerve graft harboring activated Schwann cells into the spinal cord induced Schwann cell migration beyond the graft-host barrier and facilitated regeneration of spinal axons, which was inhibited by purvalanol A pretreatment of the graft. This is the first report to our knowledge demonstrating that activation of phospho-vimentin linked to β1-integrin pathway may mediate transcellular signaling to promote axon growth.


Electrical probing of endothelial cell behaviour on a fibronectin/polystyrene/thiol/gold electrode by Faradaic electrochemical impedance spectroscopy (EIS).
The electrochemical impedance spectroscopy (EIS) technique has been shown to be an effective tool for monitoring endothelial cell behaviour on a multilayer functionalised gold electrode. Polystyrene, a reproducible model substrate, is deposited as a thin layer on a thiol functionalised gold electrode. Fibronectin, a protein promoting endothelial cell adhesion, is then adsorbed on the polystyrene surface. The different steps of this multilayer assembly are characterized by Faradaic impedance. The charge transfer resistance and the capacitance for the total layer are modified at each step according to the electrical properties of each layer. This gives the endothelial cells' electrical state in terms of its resistive and capacitive properties. In this study, the endothelial cell layer presents a specific charge transfer resistance equal to 1.55 kOmega cm(2) with no large defects in the cell layer, and a specific capacitance equal to few microF cm(-2) explained by the existence of pseudopods. These electrical properties are correlated to the endothelial cell viability, adhesion and cytoskeleton organization.


Fatal infections in a captive Pithecia irrorata (primate) by Porocephalus sp. (Pentastomida).
This work presents a case of sudden death of a non-human adult male primate, which belongs to the National Primate Center (CENP - Ananindeua - Pará - Brazil). The specimen was necropsied, and the anatomicopathologic exam showed a great collection of clotted blood in the right thoracic cavity, forming a mold. The aorta revealed an extensive lesion in its intima with a disruption area in its tissue. In the lungs, three encapsulated parasites were observed in subpleural location, specifically in the diaphragmatic, right apical and accessory lobes, measuring 05 mm diameter, which revealed a C-form by transparency analysis, characteristic of the nymphal stage of Pentastomida. Two cysts were dissected and the parasites demonstrated structural and morphometric patterns compatible with the nymph of Porocephalus. Histologically, encapsulated parasites were observed in the lungs, with inflammatory reaction in the underlying parenchyma, presence of exudate composed of fibrin, macrophages, detaching the eosinophils and presenting no granulomatous reaction. The aortic adventitial tissue presented development of granulation tissue, deposit of fibroid material in its margins, prevalence of eosinophils and free blood. The macroscopic and microscopic alterations in the aorta, as well as the presence of nymphs of Pentastomida in the lungs are data that base the hypothesis that the aortic lesion was responsible for the fatal picture of internal hemorrhage, and this picture was due to the migratory process of Pentastomida.


Creation of hollow zeolite architectures by controlled desilication of Al-zoned ZSM-5 crystals.
Hollow zeolite architectures on different length scales have been obtained upon controlled desilication of Al-zoned ZSM-5 zeolites in alkaline medium. The hollow ZSM-5 crystals possess a functional Al-rich exterior and a tunable internal porosity and accessibility.


[Morphological placental findings in intrauterine death (author's transl)].
Morphological placental findings of 46 stillborn infants are discussed and, heeding the present literature, the significance of such examinations in the scope of practical perinatology from a pathological point of view in routine diagnosis is evaluated.