The evaluation of olfactory function in individuals with chronic halitosis.
Halitosis and olfactory dysfunction may disrupt an individual's quality of life remarkably. One may ask whether halitosis has effects on olfactory functions or not? Thus, the aim of this study was to evaluate the olfactory abilities of subjects with chronic halitosis evaluated using the measurements of volatile sulfur compounds. This study was carried out in 77 subjects, with a mean age of 40.1±13.3 years, ranging from 18 to 65 years. Forty-three participants were diagnosed as halitosis according to the gas chromatography results and constituted the halitosis group. Also, a control group was created from individuals without a complaint of halitosis and also who had normal values for volatile sulfur compounds. Each subject's orthonasal olfactory and retronasal olfactory functions were assessed using "Sniffin' Sticks" and retronasal olfactory testing. The results showed that odor threshold scores were lower in participants with halitosis compared with controls. Also, hyposmia was seen more common in the halitosis group than in controls. Moreover, a significant negative correlation was found between odor threshold scores and volatile sulfur compounds levels, particularly with hydrogen sulfide and dimethyl sulfide levels. The results suggest that the chronic presence of volatile sulfur compounds may have a negative effect on olfactory function.


Simultaneous Motion and Distortion Correction Using Dual-Echo Diffusion-Weighted MRI.
Geometric distortions resulting from large pose changes reduce the accuracy of motion measurements and interfere with the ability to generate artifact-free information. Our goal is to develop an algorithm and pulse sequence to enable motion-compensated, geometric distortion compensated diffusion-weighted MRI, and to evaluate its efficacy in correcting for the field inhomogeneity and position changes, induced by large and frequent head motions. Dual echo planar imaging (EPI) with a blip-reversed phase encoding distortion correction technique was evaluated in five volunteers in two separate experiments and compared with static field map distortion correction. In the first experiment, dual-echo EPI images were acquired in two head positions designed to induce a large field inhomogeneity change. A field map and a distortion-free structural image were acquired at each position to assess the ability of dual-echo EPI to generate reliable field maps and enable geometric distortion correction in both positions. In the second experiment, volunteers were asked to move to multiple random positions during a diffusion scan. Images were reconstructed using the dual-echo correction and a slice-to-volume registration (SVR) registration algorithm. The accuracy of SVR motion estimates was compared to externally measured ground truth motion parameters. Our results show that dual-echo EPI can produce slice-level field maps with comparable quality to field maps generated by the reference gold standard method. We also show that slice-level distortion correction improves the accuracy of SVR algorithms as slices acquired at different orientations have different levels of distortion, which can create errors in the registration process. Dual-echo acquisitions with blip-reversed phase encoding can be used to generate slice-level distortion-free images, which is critical for motion-robust slice to volume registration. The distortion corrected images not only result in better motion estimates, but they also enable a more accurate final diffusion image reconstruction.


Synergistic Bacteria Killing through Photodynamic and Physical Actions of Graphene Oxide/Ag/Collagen Coating.
Researchers have widely agreed that the broad spectrum antibacterial activity of silver nanoparticles (AgNPs) can be predominantly ascribed to the action of Ag+. This study marks the first report detailing the rapid and highly efficient synergistic bacteria killing of AgNPs, which is achieved by inspiring AgNPs' strong photocatalytic capability to rapidly produce radical oxygen species using 660 nm visible light together with the innate antimicrobial ability of Ag+. These AgNPs were uniformly distributed into well-defined graphene oxide (GO) nanosheets through an in situ reduction of Ag+ and subsequently wrapped with a thin layer of type I collagen. In vivo subcutaneous tests demonstrated that 20 min irradiation of 660 nm visible light could achieve a high antibacterial efficacy of 96.3% and 99.4% on the implant surface against Escherichia coli and Staphylococcus aureus, respectively. In addition, the collagen could reduce the coatings' possible cytotoxicity. The results of this work can provide a highly effective and universal GO-based bioplatform for combination with inorganic antimicrobial NPs (i.e., AgNPs) with excellent photocatalytic properties, which can be utilized for facile and rapid in situ disinfection, as well as long-term prevention of bacterial infection through the synergistic bacteria killing of both 660-nm light-inspired photodynamic action and their innate physical antimicrobial ability.


Effects of occupational therapy home service on patients with rheumatoid arthritis.
Because there is little information about the efficacy of home occupational therapy, we decided to assess the effects of a home service on patients with rheumatoid arthritis. 105 patients aged 18-70 years, on stable medical therapy, were randomised to receive a 6-week comprehensive programme of occupational therapy (experimental group, 53 patients) or to receive no such treatment (control group, 52). At 6 weeks, control patients received the experimental regimen, and experimental patients were continued on treatment as needed up to 12 weeks. Outcomes were measured at baseline, 6, and 12 weeks with a global functional capacity score (functional score). At 6 weeks the functional score for the experimental group was significantly higher than that for the control group (mean difference = 8.1, 95% Cl 1.7 to 15.8, p = 0.012). Control patients at 12 weeks showed a similar improvement to experimental patients at 6 weeks, and between 6 and 12 weeks the experimental patients were stable. Occupational therapy leads to a statistically significant and clinically important improvement in function in patients with rheumatoid arthritis.


Rhizophydium brooksianum sp. nov., a multipored chytrid from soil.
Rhizophydium136 was isolated from pollen bait placed in a water culture containing garden soil from Penobscot County, Maine. It is an important isolate because its entire mitochondrial genome has been sequenced and it is the representative member of the Chytridiales in a fungal phylogeny based on mitochondrial protein sequences. Also, this isolate is included in an 18S rDNA, chytrid phylogeny. On nutrient agar, many inflated rhizoidal axes extend from the base of the zoosporangium, zoosporangia mature in 3 d and zoospores discharge through numerous, lenticular, discharge pores. Smooth-walled resting spores form in crowded cultures. Zoospores are a variation of the Rhizophydium subtype. This chytrid differs from R. sphaerotheca sensu Barr and because it cannot be placed in a described species it herein is described as Rhizophydium brooksianum sp. nov. Many of the differences between Rhizophydium brooksianum and other multipored Rhizophydium isolates were observed only in pure culture. Attributing a spherical, multipored Rhizophydium to a species that was described without developmental information from pure culture is untenable. Epitypes or neotypes for inadequately characterized species need to be selected, and cultures made available.


Tobacco-, alcohol-, and drug-attributable deaths and their contribution to mortality disparities in a cohort of homeless adults in Boston.
We quantified tobacco-, alcohol-, and drug-attributable deaths and their contribution to mortality disparities among homeless adults. We ascertained causes of death among 28 033 adults seen at the Boston Health Care for the Homeless Program in 2003 to 2008. We calculated population-attributable fractions to estimate the proportion of deaths attributable to tobacco, alcohol, or drug use. We compared attributable mortality rates with those for Massachusetts adults using rate ratios and differences. Of 1302 deaths, 236 were tobacco-attributable, 215 were alcohol-attributable, and 286 were drug-attributable. Fifty-two percent of deaths were attributable to any of these substances. In comparison with Massachusetts adults, tobacco-attributable mortality rates were 3 to 5 times higher, alcohol-attributable mortality rates were 6 to 10 times higher, and drug-attributable mortality rates were 8 to 17 times higher. Disparities in substance-attributable deaths accounted for 57% of the all-cause mortality gap between the homeless cohort and Massachusetts adults. In this clinic-based cohort of homeless adults, over half of all deaths were substance-attributable, but this did not fully explain the mortality disparity with the general population. Interventions should address both addiction and non-addiction sources of excess mortality.


Intensity and wavelength control of a single molecule reaction: simulation of photodissociation of cold-trapped MgH+.
Photodissociation of cold magnesium hydride ions MgH(+) leading to either Mg(+)+H or Mg+H(+) is simulated from first principles. The purpose is to study the possibility of single molecule control of the products in the presence of two laser fields. The system evolves on four electronic potential-energy curves, X(1) Sigma, A(1) Sigma, B(1) Pi, and C(1) Sigma. These potential-energy curves are calculated from first principles using multireference self-consistent field theory. The accuracy of the electronic potential curves has been checked by calculating the energies of the rovibrational eigenstates and comparing them to experimental findings. The photodissociation dynamics has furthermore been simulated by solving the time-dependent Schrodinger equation. It is shown that the branching ratio of the two dissociation channels, Mg(+)+H or Mg+H(+), can be controlled by changing the intensity and wavelength of the two driving laser fields.


Antibody Response against Severe Acute Respiratory Syndrome Coronavirus 2 Messenger Ribonucleic Acid Vaccines in Infected Individuals: A Systematic Review.
Individuals with a history of coronavirus disease 2019 (COVID-19) exhibit memory immunity acquired during natural infection. However, a decline in immunity after infection renders these individuals vulnerable to re-infection, in addition to a higher risk of infection with new variants. This systematic review examined related studies to elucidate the antibody response in these infected individuals after messenger ribonucleic acid (mRNA) vaccination. Hence, the focus of this review was to ascertain differences in the concentration of binding and neutralising antibodies of previously infected individuals in comparison to those of infection-naïve individuals after administration of two doses of mRNA vaccination through available case-control and cohort studies. Positive reverse transcriptase-polymerase chain reaction (RT-PCR) test or detectable anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies at the baseline in included studies showed categorisation of infected and uninfected individuals. This review utilised three online databases: PubMed, Scopus and Cochrane with the following keywords: (COVID-19 OR 'Coronavirus Disease 2019' OR SARS-CoV-2) AND Immun* AND (Pfizer OR BioNTech OR BNT162b2 OR Comirnaty OR Moderna OR mRNA-1273) from January 2019 to July 2021. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) 2020 guidelines and assessment based on the Crowe Critical Appraisal Tool (CCAT), we included 13 related qualified papers of observational studies discerning the binding and neutralising antibody concentrations of infected and uninfected individuals after administration of mRNA vaccines, such as the BNT162b2 and mRNA-1273 vaccine. The mRNA vaccines induced robust binding and neutralising antibody responses in both groups. However, infected individuals showed induction of higher antibody responses in a shorter time compared to uninfected individuals. Hence, a single dose of mRNA vaccination for infected individuals may be sufficient to reach the same level of antibody concentration as that observed in uninfected individuals after receiving two doses of vaccination.


Morphometric analysis of Cartesian coordinates of the human skull.
A method for locating the three dimensional coordinates of cranial landmarks with respect to the Frankfort, midsagittal, and coronal planes is presented. Sliding calipers were used to obtain the distances from left and right porion and apex to each landmark, except for a few points where spreading calipers are required. In the present example, 35 landmarks (for a total of 105 measurements) were located for each of 35 Peruvian precolumbian skulls. These distances were entered into a program (SKULL) which calculates the Cartesian coordinates of each landmark. The XYZ coordinates of each landmark contain all the information necessary for calculation of the distances between any two landmarks, and these distances may also be obtained as output from program SKULL, if desired (595 distances if all 35 landmarks are used). Reliability of the location of coordinates was determined by comparing computed distances among selected landmarks from program SKULL with traditional anthropometric measurements. Satisfactory agreements were found. Direct multivariate analysis of the coordinates of the landmarks produced insights not available in traditional multivariate analysis of conventional anthropometric measurements.


Do colon and rectum exhibit an opposite cancer risk trend versus cholecystectomy? A case--double control study.
A case-double control study on 318 personally interviewed patients with large bowel neoplasia has been carried out to establish the possible role of cholecystectomy in the development of colorectal cancer. The dietary habits both of the cancer patients and control subjects were investigated. All controls were considered free of neoplastic lesions on the basis of a negative fecal occult blood test. Data from the study showed that the prevalence of cholecystectomy in the overall patients was similar to that of the two control groups. However, analysing the data for colon and rectum, the relative risk of colonic cancer after cholecystectomy was significantly increased in males (RR = 2.75; p less than 0.05), whereas that of rectal cancer appeared to be decreased in females (RR = 0.18; p less than 0.02). Subsite analysis demonstrated that right-sided neoplasia after long-standing cholecystectomy (greater than or equal to 10 years) was responsible for the increased colonic risk. In conclusion, the present data support the hypothesis that cholecystectomy may be considered a risk factor for right-sided colon cancer, but indicate that this operation seems to play a protective role for rectal cancer.


The effect of uremia and hemodialysis on caspase-1 and caspase-3 activity in neutrophils.
Neutrophils in uremia maintain chronic inflammation, which contributes to malnutrition and immunity disorders. The influence of hemodialysis on the life span of neutrophils is unclear, although many authors postulate its apoptotic effect. Erythropoietin (EPO) is an antiapoptotic factor for various cells. We investigated factors possibly interfering in apoptosis of neutrophils in hemodialysis (HD) patients, such as HD session, parathormone (PTH), dose of EPO, inflammation and nutrition. Twenty HD patients and ten healthy controls were donors of neutrophils. We evaluated caspase-1 and caspase-3 activities, related to apoptosis of neutrophils, before and after a 4-hour HD session with cuprophane or polysulphone dialyzer. We measured serum concentrations of C-reactive protein, cholesterol, albumin, prealbumin and transferrin. Time of dialysis treatment, PTH level and dose of EPO were also evaluated. We observed a significant increase in caspase-1 activity and decrease in caspase-3 activity in neutrophils after HD with cuprophane, but not with polysulphone. Caspase-1 activity correlated positively with EPO dose and negatively with PTH level. Caspase-3 correlated negatively with the time of dialysis treatment. No correlation between caspase activity and markers of inflammation or nutrition was noticed. The results suggest that HD with bioincompatible cuprophane may prolong the life span of neutrophils due to the intense inflammatory reaction and high activity of caspase-1. Time of dialysis treatment, PTH level and EPO dose potentially influence the life span of neutrophils. PTH seems to have a proapoptotic effect of neutrophils, while EPO is an antiapoptotic factor.


Population pharmacokinetic and pharmacodynamic analyses of teicoplanin in Japanese patients with systemic MRSA infection.
Teicoplanin is a glycopeptide antibiotic used for the treatment of MRSA infection. An initial loading dose of 400 mg every 12 hours for three doses is the standard dosing regimen. This study aimed to assess whether this regimen was appropriate based on the pharmacokinetic/pharmacodynamic (PK/PD) analyses in Japanese patients. We conducted a population pharmacokinetic (PPK) analysis of teicoplanin by NONMEM using serum drug concentrations obtained from 116 patients with MRSA infection. PD of the drug was analyzed by a model assuming that the variability of therapeutic responses (assessed by body temperature, serum C-reactive protein concentrations, and white blood cell counts) on the 3rd, 7th or 14th day of treatment is associated with the logarithm of serum unbound drug concentration (Cmax,unbound) divided by the MIC against MRSA (log[Cmax,unbound/MIC]). The final PPK model showed that creatinine clearance and serum albumin concentration were significant (p < 0.01) covariates of systemic clearance and peripheral volume of distribution of teicoplanin, respectively. The PD analyses indicated that log[Cmax,unbound/MIC] of 0.30 on Day 3 of teicoplanin therapy was the threshold for achieving successful clinical responses. Integrating the PK and PD data, we consider that the standard loading dose regimen would attain the threshold serum level within the initial 3 days in only less than 50% of the patients. We propose that an extended loading regimen (400 mg every 12 hours for the first 5 doses) would be a treatment option to maximize the therapeutic effects of teicoplanin in patients with systemic MRSA infection.


TBS as a Tool to Differentiate the Impact of Antiresorptives onCortical and Trabecular Bone in Children With OsteogenesisImperfecta.
Osteogenesis imperfecta is a hereditary connective tissue disorder, resulting in low bone mass and high bone fragility. Dual-energy X-ray absorptiometry (DXA) and in adulthood also the trabecular bone score (TBS) are well established to assess bone health and fracture risk. The purpose of this investigation was to assess the usefulness of TBS in respect to different treatment regimes in children with osteogenesis imperfecta. Changes of areal bone mineral density (aBMD) and TBS using DXA scans of children treated with antiresorptive therapies were evaluated. DXA scans (aBMD, TBS) of 8 children with OI were evaluated. The scans were taken during a 1 yr period of treatment with bisphosphonates and during 1 yr pilot trial using denosumab. Changes of aBMD and TBS during both treatment regimens were compared. During bisphosphonate treatment aBMD increased about 6.2%, while TBS increased about 2.1%. The difference between aBMD and TBS before and after bisphosphonate treatment was not significant (p = 0.25). During denosumab treatment aBMD increased around 25.1%, while TBS increased 6.7%. The change of aBMD was significant (p = 0.007), as was the difference between aBMD and TBS (p < 0.001). Denosumab had a significant effect on both aBMD and TBS but was significantly more pronounced in aBMD. These results suggest a stronger effect of denosumab on cortical bone and the growth plate in comparison to bisphosphonates. Beside the lack of paediatric reference data and the small sample size, the results suggest TBS to be a useful tool for monitoring skeletal changes during development, growth, and antiresorptive therapy in children with OI.


Leukocyte adhesiveness/aggregation and neuroleptic drug treatment.
Leukocyte adhesiveness/aggregation as measured by the leukergy test was studied in peripheral citrated blood of two groups of schizophrenic patients treated with neuroleptic drugs. In the first group (N = 25) leukergy test was performed before and after commencement of neuroleptic treatment to acutely psychotic hospitalized patients. The second group studied (N = 25) were stabilized outpatients receiving long term neuroleptic medications for at least 3 months. There was a significant rise in leukergy rates between the drug free period and the subsequent measurements performed after 1 and 7 days of neuroleptic treatment in the first group (p less than 0.001). Similar high leukergy rates were noted in the second group of remitted patients. High leukergy rates were related to neuroleptic therapy and not to the psychotic state of the patients.


Southern Africa: reports document legal responses to HIV/AIDS.
A series of reports have been issued on the legal response to HIV/AIDS in eight member states of the Southern African Development Community (SADC). The states are Botswana, Malawi, Mozambique, Namibia, South Africa, Swaziland, Zambia, and Zimbabwe.


Safety of treatment with high-dose daptomycin in 102 patients with infective endocarditis.
Daptomycin is commonly used at doses >6 mg/kg/day for various indications, including infective endocarditis (IE). A systematic assessment of skeletal muscle, renal, haematological, hepatic and pulmonary toxicity of high-dose daptomycin (HDD) in IE is lacking. A total of 102 IE patients treated with HDD were included in this non-comparative, observational, single-centre cohort study conducted from 2007 to 2014. The incidence, timing, severity and evolution of adverse events (AEs) were assessed. Patients had a median age of 61.5 years and a high prevalence of co-morbidities. Staphylococci were cultured in 87.2% of cases (62.2% meticillin-resistant). The median daptomycin dose was 8.2 mg/kg/day for a median of 20 days (range, 1-60 days). HDD was withdrawn due to AEs in 12 patients (11.8%). On-treatment death occurred in 4 cases (3.9%, none HDD-related). Muscle toxicity occurred in 15 patients in a median of 15 days after HDD starts, which was largely mild and reversible with ongoing HDD use. Mild renal toxicity was observed in 9 patients (8.8%) after a median of 12 days of HDD (RIFLE-Risk in 8, Injury in 1). A rise of peripheral blood eosinophils occurred in 16 patients (15.7%). There were three cases of eosinophilic interstitial pneumonia. Four patients (3.9%) had mild allergic or idiosyncratic reactions. No other hepatic or haematological AEs were observed. Our current experience with 102 patients suggests that HDD is safe in significantly ill IE patients with multiple co-morbidities. Muscle toxicity was clinically negligible. Most importantly, there was no significant renal toxicity. Eosinophils should be carefully monitored.


Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats.
Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08) were evaluated in Sprague-Dawley albino rats with liver damage induced by thioacetamide (TAA). These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM) proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x) and level of GGT (more than 2x) in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver.


Gender differences in poststroke depression.
In stroke and other medical illnesses, secondary depression may be associated with different factors in women than in men. The authors examined 301 consecutive admissions for acute treatment of cerebrovascular accident for gender differences in depression, psychosocial factors, physical impairment, and lesion location. Women were twice as frequently diagnosed with major depression as men. Women with major depression had a greater frequency of left hemisphere lesions than men. In men, major depression was associated with greater impairment in activities of daily living, and greater severity of depression was associated with greater impairment in daily activities and social functioning. In women, greater severity of depression was associated with prior diagnosis of psychiatric disorder and cognitive impairment. These findings suggest a different nature of poststroke depression in men and women and may have implications for its treatment.


Tribolium castaneum as a whole-animal screening system for the detection and characterization of neuroprotective substances.
Parkinson's disease (PD) is a movement disorder caused by the progressive loss of dopaminergic neurons. Natural antioxidants and plant extracts with neuroprotective properties offer a promising new therapeutic approach for PD patients, but a suitable large-scale screening system is required for their discovery and preclinical analysis. Here we used the red flour beetle (Tribolium castaneum ) as a whole-animal screening system for the detection and characterization of neuroprotective substances. Paraquat was added to the diet of adult beetles to induce PD-like symptoms, which were quantified using a novel positive geotaxis behavioral assay. These paraquat-induced behavioral changes were reduced in beetles fed on diets supplemented with l-dihydroxyphenylalanine, ascorbic acid, curcumin, hempseed flour, or the Chinese herb gou-teng. T. castaneum is, therefore, a valuable model for the screening of neuroprotective substances in chemical libraries and plant extracts and could be developed as a model for the preclinical testing of therapeutic candidates for the treatment of neurodegenerative diseases, such as PD.


The optimal number and location of sutures in conduit-assisted primary digital nerve repair.
We evaluated the strength of conduit-assisted primary digital nerve repairs, with varying suture location and number, in 56 digital nerves from cadavers. Maximum load to failure was tested for the following seven repairs, designated by the number of epineurial sutures followed by the number of sutures at each end of the conduit: 4 (epineurial sutures)/0 (sutures at each end of conduit), 4/4, 4/2, 2/2, 0/4, 0/2, 0/1. The 4/4 repair (3.0 N) was significantly stronger than 4/0 (1.5 N), 2/2 (1.6 N), 0/4 (2.0 N), 0/2 (1.4 N) and 0/1 (1.1 N). Considering all repair types, there was a significant correlation between suture number and failure load, with the strongest repair having a total of 12 sutures, which is impractical. Reasonable repair options, which have two sutures at each end of the conduit and either two or no epineurial sutures, are as strong as a four-suture epineurial repair but have less sutures at the coaptation site.


Optics design of the divertor infrared television of KSTAR.
The divertor Infrared television (IR TV) system for monitoring the temperature of a divertor and localized hot spots will be installed on the upper port of the N-port in the Korea Superconducting Tokamak Advanced Research (KSTAR). The cassette of KSTAR makes a periscope inevitable for the divertor IR TV. In this article, 4 design concepts for the periscope were examined, and the design based on Keplerian was shown to have better stabilities in alignment and the vibration. The final optics design based on an f-theta lens, Keplerian, and telecentric lens was derived.


[Radical endovascular surgery of a huge cavernous internal carotid artery aneurysm of an aged patient].
A case of a huge aneurysm of the cavernous portion of the internal carotid artery (ICA) is reported. The aneurysm was successfully treated by endovascular surgery. A 78-year-old woman presenting with mild headache and cavernous sinus syndrome on the left side was incidentally disclosed to have a huge aneurysm at the cavernous portion of the left ICA by MRI and MRA. An angiogram revealed that the aneurysm had a broad neck. In view of patient's age, concomitant coronary ischemia and wide aneurysmal neck, endovascular surgery under local anesthesia was thought to be the treatment of choice. The aneurysmal sac was completely embolized with platinum coils and the ICA by a balloon proximal to the aneurysm. Over the 5 months period, the patient's symptoms has all disappeared save for mild abducens palsy. It is believed that neck clipping is the method of treatment of intracranial aneurysms. However, endovascular surgery is less invasive and may be applicable to some of high risk patients.


Radiographic caries diagnosis by clinicians in Norway and Western Australia.
In connection with continuing education courses in Norway and Western Australia (WA), dealing with caries diagnosis and treatment decisions, pre-tests were conducted. The pre-tests involved 433 dentists in Norway (ND), and 62 dentists (WAD) and 108 dental therapists (WAT) in WA, altogether 603 clinicians. Radiographs of 68 approximal surfaces were to be diagnosed and a treatment proposal was requested for each surface. ND showed the best overall diagnostic quality measured by the area beneath ROC-curve (P < 0.00001). The frequency of false-positive diagnoses (over-registrations) on sound surfaces varied between 7.1% (ND) and 11.9% (WAT) while the frequency of true-positive scores for lesions in the outer half of dentine varied from 57.4% (ND) to 48.1% (WAT). The mean numbers of restorations suggested by the three groups of clinicians were: ND: 14.3; WAD: 13.0; and WAT: 14.5. None of the differences was statistically significant. The proportion of sound surfaces proposed filled varied considerably between the groups, from 4.3% among Norwegian dentists to 10.6% among WAT (P < 0.0001). Of the lesions penetrating the outer half of dentine, the ND group would have restored 34.5% and the Australian clinicians somewhat fewer: WAD 25.6% and WAT 26.5%. The 11.3% of the ND who proposed more than two fillings on sound surfaces were responsible for 51.2% of the total number of filling proposals on sound surfaces. The corresponding numbers in the Australian group were 19.4% (WAD) and 33.3% (WAT) who made 73.6% and 75.7% of the restorative proposals on sound surfaces respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


[Communicative competence and physician - patient relationship in aboriginal health care].
Modern society consists of people from all walks of life. This melting pot of cultures might be considered both enriching and problematic. In order to communicate successfully, society members should acquire some social skills specific to a given community or, in other words, develop their communicative competence. The aim of this paper is to examine the way extralinguistic knowledge can influence physician - patient relationship in Aboriginal Australian communities. The paper is concerned with not only reviewing fundamental principles of ethnography and communicative competence but also identifying the main cultural differences that may affect the quality of healthcare services.


Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family.
The Wnt pathway regulates multiple biological and pathological processes including angiogenesis and inflammation. Here we identified a unique inhibitor of the Wnt pathway, SERPINA3K, a serine proteinase inhibitor with anti-inflammatory and angiogenic activities. SERPINA3K blocked the Wnt pathway activation induced by a Wnt ligand and by diabetes. Coprecipitation and ligand binding assay showed that SERPINA3K binds to low-density lipoprotein receptor-like protein 6 (LRP6) with a K(d) of 10 nM, in the range of its physiological concentration in the retina. Under the same conditions, SERPINA3K did not bind to the frizzled (Fz) receptor or low-density lipoprotein receptor. Further, SERPINA3K bound to LRP6 at the extracellular domain and blocked its dimerization with the Fz receptor induced by a Wnt ligand. The antagonizing activity of SERPINA3K to LRP6 was further confirmed by Xenopus axis duplication assay. These results suggest that SERPINA3K is a high-affinity, endogenous antagonist of LRP6. The blockade of Wnt signaling may represent a unifying mechanism for the anti-inflammatory and anti-angiogenic effects of SERPINA3K.


Epidural Dexamethasone Influences Postoperative Analgesia after Major Abdominal Surgery.
Epidurally administered dexamethasone might reduce postoperative pain. However, the effect of epidural administration of dexamethasone on postoperative epidural analgesia in major abdominal surgery has been doubtful. To investigate the effects and optimal dose of epidural dexamethasone on pain after major abdominal surgery. A prospective randomized, double-blind study. University hospital. One hundred twenty ASA physical status I and II men, scheduled for gastrectomy, were enrolled. Patients were randomly assigned to receive one of 3 treatment regimens (n = 40 in each group): dexamethasone 5 mg (1 mL) with normal saline (1 mL) (group D) or dexamethasone 10 mg (2 mL) (group E) or 2 mL of normal saline (group C) mixed with 8 mL of 0.375% ropivacaine as a loading dose. After the surgery, 0.2% ropivacaine - fentanyl 4 ?g/mL was epidurally administered for analgesia. The infusion was set to deliver 4 mL/hr of the PCEA solution, with a bolus of 2 mL per demand and 15 minutes lockout time. The infused volume of PCEA, intensity of postoperative pain using visual analogue scale (VAS) during rest and coughing, incidence of postoperative nausea and vomiting (PONV), usage of rescue analgesia and rescue antiemetic, and side effects such as respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, and 48 hours after the end of surgery. The resting and effort VAS was significantly lower in group E compared to group C at every time point through the study period. On the contrary, only the resting VAS in group D was lower at 2 hours and 6 hours after surgery. Total fentanyl consumption of group E was significantly lower compared to other groups. There was no difference in adverse effect such as hypotension, bradycardia, PONV, pruritis, and urinary retention among groups. Use of epidural PCA with basal rate might interrupt an accurate comparison of dexamethasone effect. Hyperglycemia and adrenal suppression were not evaluated. Epidural dexamethasone was effective for reducing postoperative pain. Especially, an epidural dexamethasone dose of 10 mg was more effective than a lower dose in patients undergoing gastrectomy which was associated with moderate to severe postoperative pain.


Signal Detection Theory as a Novel Tool to Understand Cognitive Fatigue in Individuals With Multiple Sclerosis.
Multiple Sclerosis (MS) affects 2.8 million persons worldwide. One of the most persistent, pervasive, and debilitating symptoms of MS is cognitive fatigue. While this has been known for over a century, cognitive fatigue has been difficult to study because patients' subjective (self-reported) cognitive fatigue has consistently failed to correlate with more objective measures, such as reaction time (RT) and accuracy. Here, we investigated whether more nuanced metrics of performance, specifically the metrics of Signal Detection Theory (SDT), would show a relationship to cognitive fatigue even if RT and accuracy did not. We also measured brain activation to see whether SDT metrics were related to activation in brain areas that have been shown to be sensitive to cognitive fatigue. Fifty participants (30 MS, 20 controls) took part in this study and cognitive fatigue was induced using four blocks of a demanding working memory paradigm. Participants reported their fatigue before and after each block, and their performance was used to calculate SDT metrics (Perceptual Certainty and Criterion) and RT and accuracy. The results showed that the SDT metric of Criterion (i.e., response bias) was positively correlated with subjective cognitive fatigue. Moreover, the activation in brain areas previously shown to be related to cognitive fatigue, such as the striatum, was also related to Criterion. These results suggest that the metrics of SDT may represent a novel tool with which to study cognitive fatigue in MS and other neurological populations. These results hold promise for characterizing cognitive fatigue in MS and developing effective interventions in the future.


Prior elicitation for Gaussian spatial process: An application to TMS brain mapping.
The power and commensurate prior distributions are informative prior distributions that incorporate historical data as prior knowledge in Bayesian analysis to improve inference about a phenomenon under study. Although these distributions have been developed for analyzing non-spatial data, little or no attention has been given to spatial geostatistical data. In this study, we extend these informative prior distributions to a Gaussian spatial process, which enables the elicitation of prior knowledge from historical geostatistical data for Bayesian analysis. Three informative prior distributions were developed for spatial modeling, and an efficient Markov Chain Monte Carlo algorithm was developed for performing Bayesian analysis. Simulation studies were used to assess the adequacy of the informative prior distributions. Hierarchical models combined with the developed informative prior distributions were applied to analyze transcranial magnetic stimulation (TMS) brain mapping data to gain insights into the spatial pattern of a patient's response to motor cortex stimulation. The study quantified the uncertainty in motor response and found that the primary motor cortex of the hand is responsible for most of the movement of the right first dorsal interosseous muscle. The findings provide a deeper understanding of the neural mechanisms underlying motor function and ultimately aid the improvement of treatment options for individuals with health issues.


The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors.
Proneural factors represent <10 transcriptional regulators required for specifying all of the different neurons of the mammalian nervous system. The mechanisms by which such a small number of factors creates this diversity are still unknown. We propose that proteins interacting with proneural factors confer such specificity. To test this hypothesis we isolated proteins that interact with Math1, a proneural transcription factor essential for the establishment of a neural progenitor population (rhombic lip) that gives rise to multiple hindbrain structures and identified the E-protein Tcf4. Interestingly, haploinsufficiency of TCF4 causes the Pitt-Hopkins mental retardation syndrome, underscoring the important role for this protein in neural development. To investigate the functional relevance of the Math1/Tcf4 interaction in vivo, we studied Tcf4(-/-) mice and found that they have disrupted pontine nucleus development. Surprisingly, this selective deficit occurs without affecting other rhombic lip-derived nuclei, despite expression of Math1 and Tcf4 throughout the rhombic lip. Importantly, deletion of any of the other E-protein-encoding genes does not have detectable effects on Math1-dependent neurons, suggesting a specialized role for Tcf4 in distinct neural progenitors. Our findings provide the first in vivo evidence for an exclusive function of dimers formed between a proneural basic helix-loop-helix factor and a specific E-protein, offering insight about the mechanisms underlying transcriptional programs that regulate development of the mammalian nervous system.


Representation in Aphasia Research: An Examination of U.S. Treatment Studies Published Between 2009 and 2019.
The external validity of aphasia treatment research relies on diverse and representative participants. The purposes of this study were (a) to examine whether reporting of patient-reported age, sex, and race/ethnicity has improved since Ellis (2009) and (b) to evaluate whether these demographic variables were consistent with population-level estimates of stroke survivor demographics in the United States. A scoping review examined U.S.-based aphasia treatment studies published between 2009 and 2019 and characterized the percentage of studies reporting age, sex, and race/ethnicity. Summary statistics for these variables were calculated and compared statistically with a population-based study of stroke survivors. It was found out that 97.1% of studies reported age, 93.5% reported sex, and 28.1% reported race and/or ethnicity. Within reporting studies, participant mean age was 58.04 years, 61.6% of participants were men, and 38.4% were women; 86.5% of participants were White, 11.0% were Black, 2.0% were Hispanic/Latino, and 0.5% fell in other racial categories. All three variables were statistically different from the study of Kissela et al. (2012). Despite being highlighted as an issue by Ellis (2009), less than 30% of recent aphasia treatment studies reported race or ethnicity, and participants do not appear to be demographically representative compared with estimates of stroke survivors living in the United States. These issues may negatively impact the ecological validity of aphasia treatment research. Aphasia researchers should more consistently report participant race and ethnicity and follow current guidelines for increasing the demographic representation of women and minorities.


Comparative study of laparoscopic L5-S1 fusion versus open mini-ALIF, with a minimum 2-year follow-up.
Anterior lumbar interbody fusion (ALIF) is a widely accepted tool for management of painful degenerative disc disease. Recently, the modern laparoscopic surgical technique has been combined with ALIF procedure, with good early postoperative results being reported. However, the benefit of laparoscopic fusion is poorly defined compared with its open counterpart. This study aimed to compare perioperative parameters and minimum 2-year follow-up outcome for laparoscopic and open anterior surgical approach for L5-S1 fusion. The data of 54 consecutive patients who underwent anterior lumbar interbody fusion (ALIF) of L5-S1 from 1997 to 1999 were collected prospectively. More than 2-years' follow-up data were available for 47 of these patients. In all cases, carbon cage and autologous bone graft were used for fusion. Twenty-five patients underwent a laparoscopic procedure and 22 an open mini-ALIF. Three laparoscopic procedures were converted to open ones. For perioperative parameters only, the operative time was statistically different (P=0.001), while length of postoperative hospital stay and blood loss were not. The incidence of operative complications was three in the laparoscopic group and two in the open mini-ALIF group. After a follow-up period of at least 2 years, the two groups showed no statistical difference in pain, measured by visual analog scale, in the Oswestry Disability Index or in the Patient Satisfaction Index. The fusion rate was 91% in both groups. The laparoscopic ALIF for L5-S1 showed similar clinical and radiological outcome when compared with open mini-ALIF, but significant advantages were not identified, despite its technical difficulty.


Rate of disappearance of labeled carbon dioxide from the lungs of humans during breath holding: a method for studying the dynamics of pulmonary CO2 exchange.
The dynamics of CO(2) exchange in the lungs of man was studied by observing the rate of disappearance of a stable isotope of CO(2) ((13)CO(2)) from the alveolar gas during breath holding. Over 50% of the inspired isotope disappeared within the first 3 sec followed by a moderately rapid logarithmic decline in which one-half of the remaining (13)CO(2) disappeared every 10 sec. The large initial disappearance of (13)CO(2) indicated that alveolar (13)CO(2) equilibrated in less than 3 sec with the CO(2) stored in the pulmonary tissues and capillary blood. The volume of CO(2) in the pulmonary tissues calculated from this initial disappearance was 200 ml or 0.33 ml of CO(2) per milliliter of pulmonary tissue volume. The alveolar to end-capillary gradient for (13)CO(2) was calculated by comparing the simultaneous disappearance rates of (13)CO(2) and acetylene. At rest and during exercise this gradient for (13)CO(2) was either very small or not discernible, and diffusing capacity for CO(2) (D(LCO2)) exceeded 200 ml/(min x mm Hg). After the administration of a carbonic anhydrase inhibitor the rate of disappearance of (13)CO(2) decreased markedly. D(LCO2) fell to 42 ml/(min x mm Hg) and at least 70% of the exchange of (13)CO(2) with the CO(2) stores in the pulmonary tissues and blood was blocked by the inhibitor. These changes were attributed to impairment of exchange of (13)CO(2) with the bicarbonate in the pulmonary tissues and blood. The pH of the pulmonary tissues (V(tis)) was determined by a method based on the premise that the CO(2) space in the pulmonary tissues blocked by the inhibitor represented total bicarbonate content. At an alveolar P(CO2) of 40 mm Hg pH of V(tis) equalled 6.97 +/- 0.09.


Waste polypropylene plastic conversion into liquid hydrocarbon fuel for producing electricity and energies.
Thermal degradation of polypropylene (PP) waste plastic is batched process studied for the purpose of converting waste PP into liquid hydrocarbon fuel and useful chemicals. The stainless steel reactor is used for conversion to fuel; this reactor chamber has a diameter of 6 inches, height of 18 inches and a temperature input capacity of 500 degrees C. The temperature of 150-370 degrees C was used for PP conversion into fuel. We have also used 1 kg PP waste plastic for conversion into fuel and HZSM-5 catalyst of 5% by preference was used by total weight of sample. Yield percentages obtained from PP to fuel are 92%, 2% light gas and 6% residue. Experimental finish time was 5.25 hours. By gas chromatograph/mass spectrometry instrumental analysis, the PP to fuel carbon range is found to be C3-C25,and the low sulfur level is detected by the American Society for Testing and Materials (ASTM) test method to be <1.0 ppm.


Contrasting modes of action of methylglutamate derivatives on the excitatory amino acid transporters, EAAT1 and EAAT2.
We have investigated the mechanism of action of a series of glutamate derivatives on the cloned excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2), expressed in Xenopus laevis oocytes. The compounds were tested as substrates and competitive blockers of the glutamate transporters. A number of compounds showed contrasting mechanisms of action on EAAT1 compared with EAAT2. In particular, (2S,4R)-4-methylglutamate and 4-methylene-glutamate were transported by EAAT1, with Km values of 54 microM and 391 microM, respectively, but potently blocked glutamate transport by EAAT2, with Kb values of 3.4 microM and 39 microM, respectively. Indeed, (2S,4R)-4-methylglutamate is the most potent blocker of EAAT2 yet described. (+/-)-Threo-3-methylglutamate also potently blocked glutamate transport by EAAT2 (Kb = 18 microM), but was inactive on EAAT1 as either a substrate or a blocker at concentrations up to 300 microM. In contrast to (2S,4R)-4-methylglutamate, L-threo-4-hydroxyglutamate was a substrate for both EAAT1 and EAAT2, with Km values of 61 microM and 48 microM, respectively. It seems that the chemical nature and also the orientation of the group at the 4-position of the carbon backbone of glutamate is crucial in determining the pharmacological activity. The conformations of these molecules have been modeled to understand the structural differences between, firstly, compounds that are blockers versus substrates of EAAT2 and, secondly, the pharmacological differences between EAAT1 and EAAT2.


Spiperone binding capacity in lymphocytes of patients with alcohol- and drug-induced psychosis: preliminary results.
An increased spiperone binding capacity in lymphocytes has been proposed as a possible biological marker for schizophrenia while in previous studies patients with alcohol dependence were shown to have a normal binding capacity. In a pilot study the spiperone binding capacity was studied in 8 patients with alcohol hallucinosis, 11 patients with acute drug-induced psychosis and 12 patients with other organic psychosis. An increased binding capacity, defined as > 4 fmol/l E6 cells, was found in only 1 patient with alcohol hallucinosis, 3 patients with drug-induced psychosis and 2 patients with other organic psychosis. Possible implications of these findings for future research are discussed.


Short sleep is associated with obesity among truck drivers.
Recent studies suggest that short-sleep duration is independently associated with obesity in the general population. The population of truck drivers is of particular interest, because they frequently work irregular shifts that in turn are associated with short-sleep duration. In addition, truck drivers have a high prevalence of sedentary habits, poor diet, and obesity. The present study aimed at verifying the association between sleep patterns and factors associated with obesity in this population. The study sample consisted in 4,878 truck drivers who participated in a campaign promoted by a highway company in the State of São Paulo, Brazil. This campaign offered highway truck drivers a medical and laboratorial evaluation. The truck drivers completed a questionnaire concerning demographic data, sleep duration, consumption of medications, and medical problems, such as diabetes, cardiopathy, and hypertension; as well as the Berlin questionnaire, which is able to discriminate low and high risk for obstructive sleep apnea. Blood samples were collected to measure glucose and cholesterol levels. Also, body weight and height were registered to calculate the body mass index (BMI). The mean age (+/-SD) of the truck drivers studied was 40+/-10 years. Out of the truck drivers analyzed, 28.3% (n = 1,379) had a BMI > or =30.0 Kg/m2 (obesity). Among the 4,878 drivers included in the study, 1,199 (24.6%) were on medications and 334 (6.8%) were diabetic. Drivers (26.9%) with the greater BMI had a short sleep length. The independent factors associated with obesity were sleep duration <8 h/day (OR = 1.24), age >40 years (OR = 1.20), glucose levels >200 (OR = 2.02), cholesterol levels >240 (OR = 1.57), snoring (OR = 1.74), and hypertension (OR = 2.14). Smoking was not associated with obesity (OR = 0.69), and diabetes was considered a control variable. In conclusion, this study supports the hypothesis that short sleep duration as well as age >40 years are independently associated with obesity. This particular combination (short-sleep duration and obesity) is independently associated with several healthcare problems, including high levels of cholesterol, glucose, snoring, and hypertension. However, due to the cross-sectional nature of this study, no cause-effect relationship can be drawn from these results.


Chemotherapy of gastric cancer: a review.
Gastric cancer remains a common malignancy with poor prognosis. Although surgery is possible in 80 to 90% of patients, less than 50% will have resectable disease and most of these patients will have recurrences. Many chemotherapy studies have been performed in patients with advanced carcinoma of the stomach. At least five conventional agents have been identified as having modest to moderate activity. It is unclear whether combination chemotherapy is more effective in terms of survival rate. Several new chemotherapeutic agents are being studied for gastric cancer, but none have yet proven to be more useful than conventional drugs. Although the rationale for adjuvant chemotherapy in gastric cancer is well established, a substantial number of prospective, controlled randomized trials in Western countries have failed to consistently demonstrate benefit. Thus, for patients with resectable disease who remain at high risk for recurrence, the preferred option is entry into a carefully planned investigation. In the absence of a research protocol, there are no data to support the routine use of chemotherapy in an adjuvant setting for stomach cancer.


Experimental study of the anti-atherosclerotic effect of demethylzeylasteral.
This study aimed to confirm that atherosclerosis (AS) is a systemic immune-mediated chronic inflammatory disease and to investigate the anti-atherosclerotic effect of demethylzeylasteral by testing the immunocompetent cells and inflammatory mediators in the blood and atherosclerotic plaques of the rabbit model of AS. For this purpose, 60 male New Zealand white rabbits were given 150 g high-fat diet (1% cholesterol, 5% lard, and 15% egg yolk powder) daily for a total of 90 days. On day 61, the rabbits were randomly divided into the saline group (n=15), the rosuvastatin group (n=15), the low-dose demethylzeylasteral group (n=15), and the high-dose demethylzeylasteral group (n=15). The CD3+ T lymphocytes and the subsets CD4+, CD8+, and CD4+/CD8+, as well as the soluble interleukin-2 receptor (sIL-2R) were measured before and after the treatment. The contents of immunoglobulins IgG, IgA and IgM and the levels of complements C3 and C4 were also monitored. In addition, the level of anti-oxidized low-density lipoprotein (ox-LDL) antibody, the inflammatory cytokines tumor necrosis factor-α (TNF-α), IL-6 and metalloproteinase-9 (MMP-9), the blood lipids triglyceride (TG), total cholesterol (TC), LDL cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured, and the severity of plaque lesions was also evaluated. Our results showed that the saline group, the rosuvastatin group and the low-dose demethylzeylasteral group had significantly lower activated T lymphocyte parameters CD3+, CD4+, CD8+ and CD4+/CD8+ (P<0.05), and significantly higher levels of sIL-2R, immunoglobulins IgG, IgA and IgM, complements C3 and C4, anti-ox-LDL antibody, TNF-α, IL-6 and MMP-9 (P<0.01) when compared with the high-dose demethylzeylasteral group. Moreover, TG, TC, LDL-C contents were found significantly lower and their HDL-C contents were significantly higher in high-dose demethylzeylasteral group (P<0.01) as compared to the other three groups. Furthermore, Sudan staining and haematoxylin and eosin staining of the thoracic aorta showed that, after 30-day treatment, the high-dose demethylzeylasteral group had the smoothest intima and the lightest plaque lesions among the four groups. Based on these results, we concluded that AS is a systemic immune-mediated chronic inflammatory disease and the relatively high dose of demethylzeylasteral used in the treatment of atherosclerotic rabbits could significantly alleviate AS. This implies that demethylzeylasteral may be considered as a suitable drug for anti-immunization therapy.


High frequency of normal DJH joints in B cell progenitors in severe combined immunodeficiency mice.
The severe combined immunodeficiency (scid) mouse has a defective V(D)J recombinase activity that results in arrested lymphoid development at the pro-B cell stage in the B lineage. The defect is not absolute and scid mice do attempt gene rearrangement. Indeed, approximately 15% of all scid mice develop detectable levels of oligoclonal serum immunoglobulin and T cell activity. To gain more insight into the scid defect and its effect on V(D)J rearrangement, we analyzed DJH recombination in scid bone marrow. We determined that DJH structures are present in scid bone marrow and occur at a frequency only 10-100 times less than C.B-17+/+. The scid DJH repertoire is limited and resembles fetal liver DJH junctions, with few N insertions and predominant usage of reading frame 1. Moreover, 70% of the DJH structures were potentially productive, indicating that normal V(D)J recombinants should be arising continually.


Designing of Biodegradable and Biocompatible Release and Delivery Systems of Selected Antioxidants Used in Cosmetology.
Conjugates of antioxidants p-anisic (p-AA) and vanillic (VA) acids with nontoxic, biocompatible, and biodegradedable oligo-(R,S)-(3-hydoxybutyrate) carrier were synthesized, and their structural and biological characterization was performed. The molecular structure of the bioconjugates, in which antioxidants are covalently bonded with oligo(3-hydroxybutyrate) (OHB) chains, has been proven by mass spectrometry supported by NMR. The bioconjugate hydrolytic degradation studies allowed gaining thorough insight into the hydrolysis process and confirmed the release of p-AA and VA. In vitro studies demonstrated that all of the conjugates studied were well tolerated by KB and HaCaT cell lines, as they had no marked cytotoxicity, while conjugates with a relatively short OHB carrier are optimal to support keratinocyte function. The preliminary study of the biological activity confirmed the protective effect of VA-OHB conjugates against H2O2-induced lipid peroxidation in human keratinocytes (HaCaT). It was also demonstrated that the selected bioconjugates can penetrate all layers of the skin, which shows their functionality and opens up their potential application in cosmetology.


Identification of an immunoglobulin Fc receptor of Actinobacillus actinomycetemcomitans.
Actinobacillus actinomycetemcomitans expresses proteins that bind to the Fc portion of immunoglobulins. The immunoglobulin Fc receptors on the surface of A. actinomycetemcomitans were detected by the binding of biotinylated human or murine Fc molecules to strain SUNY 465 adsorbed to the bottom of microtiter wells. Biotinylated Fc binding was inhibited by unlabeled Fc molecules and human plasma. Fc receptors were identified by the binding of biotinylated Fc molecules to bacterial membrane proteins separated by polyacrylamide gel electrophoresis and transferred to nitrocellulose. Multiple bands were identified, and the major Fc-binding protein was determined to be a heat-modifiable protein. This protein migrated with approximate molecular weights of 25,000 and 32,000 (unheated and heated, respectively). Amino-terminal sequence analysis of this protein revealed a sequence identical to the heat-modifiable protein described for A. actinomycetemcomitans ATCC 43718. This protein sequence exhibits significant homology with the N termini of outer membrane protein A (OmpA) of Escherichia coli and related OmpA-like proteins from other gram-negative bacteria.


Triatoma sanguisuga blood meals and potential for Chagas disease, Louisiana, USA.
To evaluate human risk for Chagas disease, we molecularly identified blood meal sources and prevalence of Trypanosoma cruzi infection among 49 Triatoma sanguisuga kissing bugs in Louisiana, USA. Humans accounted for the second most frequent blood source. Of the bugs that fed on humans, ≈40% were infected with T. cruzi, revealing transmission potential.


Qualitative study of the impact of an authentic electronic portfolio in undergraduate medical education.
Portfolios are increasingly used in undergraduate and postgraduate medical education. Four medical schools have collaborated with an established NHS electronic portfolio provider to develop and implement an authentic professional electronic portfolio for undergraduate students. We hypothesized that using an authentic portfolio would have significant advantages for students, particularly in familiarizing them with the tool many will continue to use for years after graduation. This paper describes the early evaluation of this undergraduate portfolio at two participating medical schools. To gather data, a questionnaire survey with extensive free text comments was used at School 1, and three focus groups were held at School 2. This paper reports thematic analysis of students' opinions expressed in the free text comments and focus groups. Five main themes, common across both schools were identified. These concerned the purpose, use and acceptability of the portfolio, advantages of and barriers to the use of the portfolio, and the impacts on both learning and professional identity. An authentic portfolio mitigated some of the negative aspects of using a portfolio, and had a positive effect on students' perception of themselves as becoming past of the profession. However, significant barriers to portfolio use remained, including a lack of understanding of the purpose of a portfolio and a perceived damaging effect on feedback.


Overcoming telomeric silencing: a trans-activator competes to establish gene expression in a cell cycle-dependent way.
Genes located near telomeres in yeast are subject to position-effect variegation. To better understand the mechanism of this variegation, we investigated how a telomeric URA3 gene switches from a silent to an expressed state. We found that silencing of a telomeric URA3 gene was attributable to the elimination of its basal transcription. The reversal of that silencing was dependent on the presence of PPR1, the trans-activator protein of URA3. Maximum expression of URA3 required a higher concentration of PPR1 when URA3 was telomeric compared with when it was at a nontelomeric location. The ability of PPR1 to overcome silencing varied at different points in the cell cycle. In cells arrested in G2/metaphase, PPR1 was able to activate transcription of a telomeric URA3, but in cells arrested in G0, G1, or early S phase it was not. In comparison, a nontelomeric URA3 could be activated by PPR1 at all times. We conclude that once established, telomeric silent chromatin is a relatively stable structure, making a gene recalcitrant to activation. Following the disassembly of silent chromatin during DNA replication, competition of assembly ensues between components of telomeric chromatin, to establish a silent state, and the trans-activator, to establish gene expression. These results help explain the stochastic nature of phenotypic switching in variegated gene expression.


The social stigma of HIV-AIDS: society's role.
AIDS is a devastating and deadly disease that affects people worldwide and, like all infections, it comes without warning. Specifically, childbearing women with AIDS face constant psychological difficulties during their gestation period, even though the pregnancy itself may be normal and healthy. These women have to deal with the uncertainties and the stress that usually accompany a pregnancy, and they have to live with the reality of having a life-threatening disease; in addition to that, they also have to deal with discriminating and stigmatizing behaviors from their environment. It is well known that a balanced mental state is a major determining factor to having a normal pregnancy and constitutes the starting point for having a good quality of life. Even though the progress in both technology and medicine is rapid, infected pregnant women seem to be missing this basic requirement. Communities seem unprepared and uneducated to smoothly integrate these people in their societies, letting the ignorance marginalize and isolate these patients. For all the aforementioned reasons, it is imperative that society and medical professionals respond and provide all the necessary support and advice to HIV-positive child bearers, in an attempt to allay their fears and relieve their distress. The purpose of this paper is to summarize the difficulties patients with HIV infection have to deal with, in order to survive and merge into society, identify the main reasons for the low public awareness, discuss the current situation, and provide potential solutions to reducing the stigma among HIV patients.


Five-factor model of personality disorder: a proposal for DSM-V.
The predominant dimensional model of general personality structure within psychology is the five-factor model (FFM). Research indicates that the personality disorders of the American Psychiatric Association's diagnostic manual can be understood as maladaptive variants of the domains and facets of the FFM. The current review provides a proposal for the classification of personality disorder from the perspective of the FFM. Discussed as well are implications and issues associated with an FFM of personality disorder, including the integration of a psychiatric nomenclature with general personality structure, the inclusion of a domain of openness to experience, the identification of problems in living associated with maladaptive personality traits, the setting of a diagnostic threshold, prototypal matching, feasibility, and clinical utility.


The SAP domain of Ku facilitates its efficient loading onto DNA ends.
The evolutionarily conserved DNA repair complex Ku serves as the primary sensor of free DNA ends in eukaryotic cells. Its rapid association with DNA ends is crucial for several cellular processes, including non-homologous end joining (NHEJ) DNA repair and telomere protection. In this study, we conducted a transient kinetic analysis to investigate the impact of the SAP domain on individual phases of the Ku-DNA interaction. Specifically, we examined the initial binding, the subsequent docking of Ku onto DNA, and sliding of Ku along DNA. Our findings revealed that the C-terminal SAP domain of Ku70 facilitates the initial phases of the Ku-DNA interaction but does not affect the sliding process. This suggests that the SAP domain may either establish the first interactions with DNA, or stabilize these initial interactions during loading. To assess the biological role of the SAP domain, we generated Arabidopsis plants expressing Ku lacking the SAP domain. Intriguingly, despite the decreased efficiency of the ΔSAP Ku complex in loading onto DNA, the mutant plants exhibited full proficiency in classical NHEJ and telomere maintenance. This indicates that the speed with which Ku loads onto telomeres or DNA double-strand breaks is not the decisive factor in stabilizing these DNA structures.


Nurses' Perceptions of Weight Gain and Obesity in the Prison Environment.
This study aimed to improve understanding of obesity in prison by investigating prison nurses' perceptions of weight gain and obesity. In-depth semistructured interviews were carried out with 17 nurses who worked in two male prisons in the United Kingdom. Nurses identified a variety of factors that they believed contributed to obesity and weight gain in the prison setting. These included factors caused by prisoner behavior, such as poor food choices and sedentary lifestyle. Factors influenced by the prison environment, such as stress of imprisonment, prison regime, and prison culture, were also seen as significant. These factors were seen as barriers to the role of nurses delivering care in prison. Nurses explained how they adapted their role to overcome these barriers.


Indirect Economic Impact Incurred by Haze Pollution: An Econometric and Input-Output Joint Model.
Econometrics and input-output models have been presented to construct a joint model (i.e., an EC + IO model) in the paper, which is characterized by incorporating the uncertainty of the real economy with the detailed departmental classification structure, as well as adding recovery period variables in the joint model to make the model dynamic. By designing and implementing a static model, it is estimated that the indirect economic loss for the transportation sector caused by representative haze pollution of Beijing in 2013 was 23.7 million yuan. The industrial-related indirect losses due to the direct economic losses incurred by haze pollution reached 102 million yuan. With the constructed dynamic model, the cumulative economic losses for the industrial sectors have been calculated for the recovery periods of different durations. The results show that: (1) the longer the period that an industrial department returns to normal output after haze pollution has impacted, the greater the cumulative economic loss will be; (2) when the recovery period is one year, the cumulative economic loss value computed by the dynamic EC + IO model is much smaller than the loss value obtained by the static EC + IO model; (3) the recovery curves of industrial sectors show that the recovery rate at the early stage is fast, while it is slow afterwards. Therefore, the governance work after the occurrence of haze pollution should be launched as soon as possible. This study provides a theoretical basis for evaluating the indirect economic losses of haze pollution and demonstrates the value of popularization and application.


Health professionals' migration: the Portuguese case.
Migration of health professionals has been an important issue on the agenda of governments in recent years. The European Union directive on the recognition of professional qualifications coupled with labour shortages in the health sector has led to a growing mobility of physicians from both European countries and non-European Economic Area (EEA) countries. This study takes a deeper look at these migration phenomena in the Portuguese case. A significantly convergent dual pattern of migration is shown to emerge, in which the growth of intra-European migration has broadly continued to coexist with the maintenance of traditional overseas immigration channels.


Dietary patterns and C-peptide concentrations in a Japanese working population.
It remains unsettled whether dietary patterns play a role in insulin resistance. We assessed the association of major dietary patterns with C-peptide concentrations in a Japanese working population. A cross-sectional study was conducted in 456 municipal employees (270 men and 186 women) 21 to 67 y old who participated in a health survey at the time of their periodic checkup. The dietary patterns were derived by using the principal component analysis of the consumption of 52 food and beverage items, which was assessed by a validated brief dietary history questionnaire. Multiple regression analysis was used to estimate the means of C-peptide concentrations across tertiles of each dietary pattern score with the adjustment of potential confounders, including age, body mass index, physical activity, smoking, alcohol drinking, and energy intake. We identified three dietary patterns: healthy, animal food, and Westernized breakfast patterns. The Westernized breakfast pattern was characterized by high intakes of bread, confectionaries, and milk and yogurt but low intakes of rice and alcohol and was inversely associated with C-peptide concentrations in women but not in men. The multivariable-adjusted means of C-peptide concentrations were 1.03 ng/mL (95% confidence interval 0.95-1.12), 0.95 ng/mL (95% confidence interval 0.88-1.03), and 0.89 ng/mL (95% confidence interval 0.82-0.97) for the lowest through the highest tertiles of the Westernized breakfast pattern score (P for trend = 0.015) in women. Other dietary patterns were not appreciably associated with C-peptide concentrations. In a subgroup, similar associations were observed between dietary patterns and the homeostasis model assessment of insulin resistance. The Westernized breakfast pattern may be associated with a lower insulin resistance in Japanese women.


Challenges and recommendations for conducting epidemiological studies in the field of epilepsy pharmacogenetics.
Epilepsy is one of the most prevalent neurological disorders, afflicting approximately 50 million Indians. Owing to affordability and easy availability, use of first-generation antiepileptic drugs (AEDs) is heavily encouraged for the treatment of epilepsy in resource-limited countries such as India. Although first-generation AEDs are at par with second-generation AEDs in terms of efficacy, adverse drug reactions (ADRs) are quite common with them. This could be attributed to the inferior pharmacokinetic parameters such as nonlinear metabolism, narrow therapeutic index and formation of toxic intermediates. In addition, epilepsy patients may differ in the pharmacokinetic and pharmacodynamic profiles, with about 1/3(rd) of the population failing to respond to treatment. A proportion of this interindividual variability in response may be explained by genetic heterogeneity in the activity and expression of the network of proteins such as metabolizing enzymes, transporters and targets of AEDs. Over the last two decades, a considerable effort has been made by the scientific community for unraveling this genetic basis of variable response to AEDs. However, there have been inconsistencies in such genetic association studies conducted across different territories of the world. There could be several reasons underlying the poor replicability of these studies, mainly nonuniform phenotypic definitions, poor sample size and interethnic variability. In the present review article, we provide an overview of heterogeneity in study designs for conducting pharmacogenetic studies. In addition, critical recommendations required for overcoming such challenges imposed by pharmacogenetic epidemiological studies have been briefly discussed.


The complexity of HIV vasculopathy.
We present a case and discuss stroke related to human immunodeficiency virus (HIV) infection and the difficulties of reaching a firm diagnosis of the cause of the aneurysmal vasculopathy. In the absence of a clear aetiology we suggest looking for varicella zoster virus (VZV) replication in the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) and treating with intravenous acyclovir, aiming for HIV control with appropriate antiretroviral therapy and providing suitable antiplatelet agents. If there is a high index of suspicion of VZV, therapy with acyclovir may be prudent even if the CSF PCR is negative (as may occur after the first 2 weeks of reactivation of infection). Determination of a VZV plasma:CSF IgG ratio is not readily available and would only provide surrogate support for a previous VZV infection in the central nervous system compartment.


[A case of severe measles encephalitis in a pregnant woman].
A 23-year-old woman in her 23rd week of gestation became febrile and then developed cutaneous eruption typical of measles on July 16, 1993. Two weeks prior to this, her 8-month-old daughter has developed measles. The woman became comatose in a few days and was admitted to our hospital where coma, flaccid paralysis of all four limbs and midbrain corectopia were apparent. High titers of anti-measles antibodies were found in the serum and cerebrospinal fluid. She received a 3-day course of pulse-dose intravenous methylprednisolone, however, without effect. Her consciousness gradually improved and after 1 month, subtle volitional movements were observed. However, fetal death was found and the fetus was removed by cesarean section. In MRI T2-weighted images, earlier in her illness, high signal intensity areas were scattered deeply in the cerebral white matter and the posterior limbs of the internal capsule. However, T1-weighted image was unremarkable. Marked, diffuse cerebral atrophy was noticed 3 months later by both CT and MRI, which was accompanied by wide spread high signal intensity areas around the lateral and fourth ventricles. Regarding the pathogenesis, there are two possibilities, i.e., her encephalitis was due to direct measles viral invasion into the CNS, or due to the autoimmune processes triggered by measles infection. Immune dysfunction known to occur during pregnancy might be responsible for the severity of encephalitis the patient suffered from. A recent increase in the number of adult measles infection might be an admonition that pregnant women are not exceptional to measles infection and that the infection could give rise to a severe form of measles encephalitis.


Perceptual expertise enhances the resolution but not the number of representations in working memory.
Despite its central role in cognition, capacity in visual working memory is restricted to about three or four items. Curby and Gauthier (2007) examined whether perceptual expertise can help to overcome this limit by enabling more efficient coding of visual information. In line with this, they observed higher capacity estimates for upright than for inverted faces, suggesting that perceptual expertise enhances visual working memory. In the present work, we examined whether the improved capacity estimates for upright faces indicates an increased number of "slots" in working memory, or improved resolution within the existing slots. Our results suggest that perceptual expertise enhances the resolution but not the number of representations that can be held in working memory. These results clarify the effects of perceptual expertise in working memory and support recent suggestions that number and resolution represent distinct facets of working memory ability.


A Generative Statistical Algorithm for Automatic Detection of Complex Postures.
This paper presents a method for automated detection of complex (non-self-avoiding) postures of the nematode Caenorhabditis elegans and its application to analyses of locomotion defects. Our approach is based on progressively detailed statistical models that enable detection of the head and the body even in cases of severe coilers, where data from traditional trackers is limited. We restrict the input available to the algorithm to a single digitized frame, such that manual initialization is not required and the detection problem becomes embarrassingly parallel. Consequently, the proposed algorithm does not propagate detection errors and naturally integrates in a "big data" workflow used for large-scale analyses. Using this framework, we analyzed the dynamics of postures and locomotion of wild-type animals and mutants that exhibit severe coiling phenotypes. Our approach can readily be extended to additional automated tracking tasks such as tracking pairs of animals (e.g., for mating assays) or different species.


Studies on the peripheral action of opioids in postoperative pain in man.
Using simultaneous measurements of pain in both limbs after bilateral orthopaedic surgery, peripheral and central components of regionally administered drugs can be separated. Perineural local anesthetic action is readily shown in both upper and lower limbs. Perineural morphine had no effect in ankle blocks, although an effect superior to that of local anesthetics has been claimed in man. Similarly, no effect was seen from morphine or buprenorphine given by intravenous regional administration in the upper limbs, although opioids have shown local antinociceptive action in animal models. There is little evidence to suggest that the usual parenteral opioids have any significant peripheral action clinically, but further human studies are needed because of the theoretical importance of even a small peripheral component.


Genetic structure provides insights into the geographic origins and temporal change in the invasive charru mussel (Sururu) in the southeastern United States.
In 2004, Mytella charruana (d'Orbigny, 1842) (Mollusca: Bivalvia: Mytilidae) became established along the coast of the southeastern United States (SE-US). Using mitochondrial DNA sequencing (cytochrome c oxidase subunit I), we compared genetic variation throughout its native range in South America to its invasive range in the SE-US. Samples from the SE-US were collected in 2006 and 2010 enabling a temporal comparison to evaluate possible genetic changes of the invasive population. We addressed two questions. First, what are the potential source populations (or geographic regions) for the SE-US invasion? Second, how has genetic diversity changed between the two sampling periods within the SE-US? We identified a total of 72 haplotypes, 64 of which were isolated to geographic sites and only 8 were shared among sites. The highly structured native range provides insight into the origin of invasive populations where our results suggest that the introduced SE-US population originated from multiple source populations with the Panama region as the primary source. Additionally, our results indicate that genetic composition of the non-native populations was unchanged between the two sampling periods. Mytella charruana exhibit a significant pattern of genetic structure among natural populations, owing to biogeographic barriers that limit natural dispersal, and an ability to persist in novel habitats, owing to a suite of life-history characters that favor survival under variable conditions. Overall, this study explains why M. charruana may become an increasing threat to locations founded by anthropogenic transportation.


Patient Comorbidity and Serious Adverse Events after Outpatient Colonoscopy: Population-based Study From Three States, 2006 to 2009.
Serious GI adverse events in the outpatient setting were examined for patients with a full spectrum of comorbid conditions and combinations of multiple comorbidities. This is a retrospective follow-up study. Ambulatory surgery and hospital discharge data sets from California, Florida, and New York, 2006 to 2009, were used. The outpatient colonoscopies of 4,234,084 adults aged 19 to 85 and over and payers were examined. Thirty-day hospitalizations due to colonic perforations and GI bleeding, measured as cumulative outcomes, were investigated. About 24% of patients undergoing outpatient colonoscopy had a comorbid condition. In comparison with patients without comorbidities, the adjusted risks of adverse events were greater for patients with several single comorbidities and combinations of multiple comorbid conditions. Elderly patients and those treated in freestanding Ambulatory Surgery Centers had higher odds of colonic perforations and GI bleeding than younger patients and patients treated in hospital outpatient departments. The study was constrained by limitations inherent in administrative data. Given the large number of outpatient colonoscopies performed in the United States, these procedures should be provided with caution to patients with chronic and multiple comorbidities and the elderly, because these populations are associated with higher rates of colonic perforations and GI bleeding.


Prognostic Implication and Oncogenic Role of PNPO in Pan-Cancer.
Objective: Pyridoxine 5'-phosphate oxidase (PNPO) is a key enzyme in the metabolism of vitamin B6 and affects the tumorigenesis of ovarian and breast cancers. However, the roles of PNPO in other types of cancer remain unknown. Methods: The expression of PNPO was interpreted by The Cancer Genome Atlas (TCGA) database and Genotype Tissue-Expression (GTEX) database. Analysis of PNPO genomic alterations and protein expression in human organic tissues was analyzed by the cBioPortal database and human multiple organ tissue arrays. PNPO with drug sensitivity analysis was performed from the CellMiner database. The correlations between PNPO expression and survival outcomes, clinical features, DNA mismatch repair system (MMR), microsatellite instability (MSI), tumor mutation burden (TMB), and immune-associated cell infiltration were analyzed using the TCGA, ESTIMATE algorithm, and TIMER databases. Gene Set Enrichment Analysis (GSEA) was applied to elucidate the biological function of PNPO in pan-cancer. Results: The differential analysis showed that the level of PNPO mRNA expression was upregulated in 21 tumor types compared with normal tissues, which was consistent with its protein expression in most cancer types. The abnormal expression of PNPO could predict the survival outcome of patients with esophageal carcinoma (ESCA), kidney renal clear cell carcinoma (KIRC), prostate adenocarcinoma (PRAD), ovarian serous cystadenocarcinoma (OV), and uveal melanoma (UVM). Furthermore, the most frequent mutation type of PNPO genomic was amplified. Moreover, the aberrant PNPO expression was related to MMR, MSI, TMB, and drug sensitivity in various types of cancer. The expression of PNPO was related to the infiltration levels of various immune-associated cells in pan-cancer by ESTIMATE algorithm and TIMER database mining. Conclusion: Our results suggest that PNPO is a potential molecular biomarker for predicting patient prognosis, drug sensitivity, and immunoreaction in pan-cancer.


Forkhead box C1 promoter upstream transcript, a novel long non-coding RNA, regulates proliferation and migration in basal-like breast cancer.
Recent studies have shown that long non‑coding RNAs (lncRNAs) have crucial regulating roles in carcinogenesis. Forkhead box C1 (FOXC1) is an important cancer‑associated gene in basal‑like breast cancer (BLBC). In the present study, a novel lncRNA, FOXC1 promoter upstream transcript (FOXCUT) was investigated in BLBC patients using polymerase chain reaction analysis. The results showed that the expression of FOXCUT and FOXC1 were positively correlated. When the expression of FOXCUT was downregulated by small interfering RNA, the expression of FOXC1 was similarly reduced. Furthermore, in MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells, knockdown of FOXCUT markedly inhibited cell proliferation and migration in vitro. In conclusion, FOXCUT lncRNA may be functionally involved in the tumor progression of BLBCs through the regulation of its paired mRNA, FOXC1, demonstrating that FOXCUT may serve as a novel biomarker and therapeutic target in BLBCs.


Vitellogenin titres in normal and accelerated maturation of gregarious-phase Schistocerca gregaria.
Isolation of vitellogenin of the Schistocerca gregaria (Forskal) in its gregarious phase was achieved by a combination of gel permeation and anion exchange chromatography. Staining for carbohydrate and lipid moieties showed that the vitellogenin is a glycolipoprotein. The vitellogenin of S. gregaria has a native molecular weight of about 700 kDa. On SDS-PAGE, the protein showed nine apoproteins of about 124, 120, 105, 60, 59, 58, 57, 53 and 34 kD. Determination of the levels of vitellogenin by ELISA in the haemolymph of maturing females showed that those exposed to mature males from 1 to 2 days after ecdysis had increased levels of vitellogenin from day 10 (81.1 +/- 4.5). In contrast, females exposed to immature males or kept alone showed an increase (107.3 +/- 0.9 and 70.2 +/- 2.7) not until day 16 or later, respectively. These results are consistent with the accelerating effect of pheromonal emissions from mature males on the maturation of female S. gregaria.


Involvement of the central noradrenergic system in opioid modulation of luteinizing hormone and prolactin secretion in the pig.
The role of norepinephrine (NE) in the progesterone (P)-dependent endogenous opioid peptide (EOP) suppression of LH and prolactin (PRL) secretion in the pig was studied. Fifteen ovariectomized gilts treated with P (0.85 mg/kg b.w. i.m.) twice daily for 10 days were assigned, 5 gilts each, to the following treatment groups: 1) control, 2) AIMAX (N-methyl-N1[1-methyl-2-propenyl]1,2 hydrazinedicarbothioamide), and 3) anti-GnRH serum. On day 4 of P treatment, AIMAX (125 mg per 1.8 kg feed/day), previously shown to be an NE synthesis inhibitor, was fed daily for 7 days to group 2. On the last day of P treatment, group 3 gilts received an i.v. injection of anti-GnRH serum at 0800 h while Group 1 animals received an i.v. injection of serum collected from hypophysectomized gilts. Jugular blood samples were collected every 15 min for 9 h starting at 1000 h. All gilts received two injections of naloxone (NAL; 1 mg/kg b.w., i.v.) at 1400 h and 1600 h and an injection of a GnRH analogue (D-[Ala6-desGly-NH10]-ethylamide; 5 micrograms/pig, i.v.) at 1800 h. Pretreatment serum LH concentrations were lower (p < 0.05) in AIMAX-treated gilts (0.19 +/- 0.09 ng/ml) than in controls (0.53 +/- 0.09 ng/ml), but were similar to those in GnRH antiserum-treated gilts (0.32 +/- 0.09 ng/ml). NAL increased (p < 0.001) serum LH concentrations in control animals and averaged 1.6 +/- 0.2 ng/ml the first h. AIMAX and anti-GnRH serum blocked the NAL-induced LH secretion. Serum PRL concentrations averaged 6.0 +/- 0.1 ng/ml for all groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Abundance of dioxygenase genes similar to Ralstonia sp. strain U2 nagAc is correlated with naphthalene concentrations in coal tar-contaminated freshwater sediments.
We designed a real-time PCR assay able to recognize dioxygenase large-subunit gene sequences with more than 90% similarity to the Ralstonia sp. strain U2 nagAc gene (nagAc-like gene sequences) in order to study the importance of organisms carrying these genes in the biodegradation of naphthalene. Sequencing of PCR products indicated that this real-time PCR assay was specific and able to detect a variety of nagAc-like gene sequences. One to 100 ng of contaminated-sediment total DNA in 25-microl reaction mixtures produced an amplification efficiency of 0.97 without evident PCR inhibition. The assay was applied to surficial freshwater sediment samples obtained in or in close proximity to a coal tar-contaminated Superfund site. Naphthalene concentrations in the analyzed samples varied between 0.18 and 106 mg/kg of dry weight sediment. The assay for nagAc-like sequences indicated the presence of (4.1 +/- 0.7) x 10(3) to (2.9 +/- 0.3) x 10(5) copies of nagAc-like dioxygenase genes per microg of DNA extracted from sediment samples. These values corresponded to (1.2 +/- 0.6) x 10(5) to (5.4 +/- 0.4) x 10(7) copies of this target per g of dry weight sediment when losses of DNA during extraction were taken into account. There was a positive correlation between naphthalene concentrations and nagAc-like gene copies per microgram of DNA (r = 0.89) and per gram of dry weight sediment (r = 0.77). These results provide evidence of the ecological significance of organisms carrying nagAc-like genes in the biodegradation of naphthalene.


Isotopomeric polymorphism.
The complex formed between 4-methylpyridine and pentachlorophenol (4MPPCP) crystallizes in a triclinic space group. If the same complex is synthesized from deuterated pentachlorophenol (4MPPCP-d1), it crystallizes in an entirely different monoclinic polymorph. Solid-state NMR of samples synthesized with a full range of deuteration levels, crystallized from solution or the melt, and in the presence or absence of seeds confirms that the isotopomers indeed have different thermodynamically stable crystal structures. The phenomenon is apparently due to very different hydrogen bond strengths between the two polymorphs.


The Psoriasis Therapeutic Potential of a Novel Short Laminin Peptide C16.
Psoriasis is a chronic inflammatory skin disease characterized by excessive growth of keratinocytes and hyperkeratosis in the epidermis. An abnormality of the non-lesional epidermis at an early stage of psoriasis is involved in triggering inflammatory cell infiltration into the dermis. Integrin α5β1 acts as a receptor for fibronectin and has been found to be overexpressed in non-lesional psoriatic epidermis. To investigate whether α5β1 integrin has a potential as a drug target for psoriasis treatment, the α5β1 integrin-binding peptide, C16, was used to obstruct the HaCat keratinocyte cellular responses induced by fibronectin (Fn) in culture and psoriasis-like skin inflammation induced in mice by imiquimod (IMQ). The C16 exhibited antagonistic activity against α5β1 integrin in HaCat cells, with evidence of suppression of the Fn-mediated proliferative, cytoskeletal, and inflammatory responses. Topical treatment with C16 greatly reduced the IMQ-induced epidermal hyperplasia, infiltration of neutrophils/macrophages, and expression of pro-inflammatory mediators in mouse skin. The C16SP (C16-derived short peptide; DITYVRLKF) also exhibited antagonistic activity, suppressing α5β1 integrin activity in culture, and reducing IMQ-induced skin inflammation. Taken together, this study provides the first evidence that α5β1 integrin may be a potential drug target for psoriasis. The synthetic C16 peptide may serve as an agent for psoriasis therapy.


Function of ventricular pacemakers during resuscitation.
The reciprocal effects of resuscitation and permanent, ventricular-inhibited pacemakers were examined in four, well-documented cases of witnessed out-of-hospital arrest. The resulting observations provide useful insight in the treatment of cardiac arrest in the large number of patients with permanent pacemakers. Transient sensing malfunctions occurred in the two patients in whom direct current countershocks were not required and were probably related to the severely deranged state of the myocardium. In spite of periods of asynchronous pacing in this critically unstable setting, no arrhythmias were precipitated. In the two patients who required defibrillation, transient malfunctions of pacing, capture and sensing occurred in spite of protective electronics in the pacing system, the left-sided location of the generator and, in one patient, the bipolar configuration. The pacemaker appeared to intermittently sense coarse ventricular fibrillatory waves. The malfunctions in the two latter cases were probably the result of the combined effects of the countershock and the abnormal state of the myocardium. All four patients succumbed, three in the emergency room and one on the eighth hospital day. Outcome was predominantly determined by the patient's response to therapeutic interventions. The observed pacemaker malfunctions, although potentially life-threatening, had no obvious, adverse effect on outcome in these four cases, mainly because of the transient nature of the abnormalities. Indeed, in one case, the presence of pacemaker activity was pivotal in identifying the native rhythm, illustrating the diagnostic potential of this analytical approach.


Structural Analysis of Human Cofilin 2/Filamentous Actin Assemblies: Atomic-Resolution Insights from Magic Angle Spinning NMR Spectroscopy.
Cellular actin dynamics is an essential element of numerous cellular processes, such as cell motility, cell division and endocytosis. Actin's involvement in these processes is mediated by many actin-binding proteins, among which the cofilin family plays unique and essential role in accelerating actin treadmilling in filamentous actin (F-actin) in a nucleotide-state dependent manner. Cofilin preferentially interacts with older filaments by recognizing time-dependent changes in F-actin structure associated with the hydrolysis of ATP and release of inorganic phosphate (Pi) from the nucleotide cleft of actin. The structure of cofilin on F-actin and the details of the intermolecular interface remain poorly understood at atomic resolution. Here we report atomic-level characterization by magic angle spinning (MAS) NMR of the muscle isoform of human cofilin 2 (CFL2) bound to F-actin. We demonstrate that resonance assignments for the majority of atoms are readily accomplished and we derive the intermolecular interface between CFL2 and F-actin. The MAS NMR approach reported here establishes the foundation for atomic-resolution characterization of a broad range of actin-associated proteins bound to F-actin.


Autologous hematopoietic stem cell transplantation for severe autoimmune disease with special reference to rheumatoid arthritis.
In 1996 an international collaboration began to explore the use of immunoablation and stem cell rescue in the treatment of severe autoimmune disease. Around 500 patients have been so treated according to consensus guidelines, the majority being registered in the combined European League Against Rheumatism and European Group for Blood and Marrow Transplantation (EULAR/EBMT) data registry. Results in terms of toxicity and benefit are different in the different autoimmune diseases, e.g., for rheumatoid arthritis (RA) a low transplant related mortality (TRM) of one patient out of 43 but high relapse rate (around two-thirds), whereas for systemic sclerosis (SSc) a higher TRM (12%) but less relapse. More aggressive immunoablative regimes were associated with more procedure related toxicity, but so far a clear therapeutic advantage has not been demonstrated. An overall actuarial TRM of 9% was observed. Randomized, prospective controlled phase III trials have begun in SSc and will soon commence in RA and multiple sclerosis. More phase I and II data are required for systemic lupus erythematosus and juvenile idiopathic arthritis.


Updated research nosology for HIV-associated neurocognitive disorders.
In 1991, the AIDS Task Force of the American Academy of Neurology published nomenclature and research case definitions to guide the diagnosis of neurologic manifestations of HIV-1 infection. Now, 16 years later, the National Institute of Mental Health and the National Institute of Neurological Diseases and Stroke have charged a working group to critically review the adequacy and utility of these definitional criteria and to identify aspects that require updating. This report represents a majority view, and unanimity was not reached on all points. It reviews our collective experience with HIV-associated neurocognitive disorders (HAND), particularly since the advent of highly active antiretroviral treatment, and their definitional criteria; discusses the impact of comorbidities; and suggests inclusion of the term asymptomatic neurocognitive impairment to categorize individuals with subclinical impairment. An algorithm is proposed to assist in standardized diagnostic classification of HAND.