Chloracne following environmental contamination by TCDD in Seveso, Italy.
Data are presented on the occurrence of chloracne, clinical symptoms and biochemical changes in 164 children following environmental contamination by TCDD from an industrial accident in Seveso, Italy. An overall positive association was found between the territorial distribution of chloracne cases and the different levels of soil contamination in the affected area. Individual risk factors such as condition and length of exposure, intake via contaminated foods, etc. were evaluated; no single factor appeared to be associated with chloracne. Disturbances of the gastrointestinal tract were more frequently observed in children affected with chloracne in those from the same areas having no skin lesions. However, no clinically definable systemic disease has been diagnosed.


Autonomic dysfunction is common in liver cirrhosis and is associated with cardiac dysfunction and mortality: prospective observational study.
Although autonomic dysfunction has been shown to be associated with liver cirrhosis, the prevalence and prognostic implications are unclear. Abnormal heart rate variability (HRV), a measure of autonomic function, has not been well investigated in cirrhosis. To evaluate the prevalence of high-risk HRV parameters in a cohort of cirrhotic patients and their association with cardiac dysfunction and mortality. Prospective observational study conducted in the Federal University of São Paulo. A cohort of 120 patients, comprising 17 healthy controls and 103 cirrhotic outpatients, was evaluated and followed for 10 months. HRV analysis was based on 24-hour Holter monitoring and defined using time-domain and frequency-domain parameters. The HRV parameters were statistically lower in cirrhotic patients than in healthy subjects. High-risk HRV parameters were prevalent, such that 64% had at least one high-risk parameter. Time-domain parameters correlated with Child scores (P < 0.0001). In regression models, HRV parameters were independent predictors of diastolic dysfunction and mortality. During 10 months of follow-up, there were 11 deaths, all of patients with at least one high-risk HRV parameter. Kaplan-Meier analysis estimated low survival rates among patients with standard deviation of normal-to-normal RR intervals (SDNN) < 100. Reduced HRV is prevalent in liver cirrhosis and is related to cardiac dysfunction, severity of liver disease and mortality. Abnormal high-risk HRV parameters are prevalent among cirrhotic patients and are also predictors of mortality. Our findings highlight the need for a more careful cardiac evaluation of cirrhotic patients.


The ubiquitin-specific protease USP17 prevents cellular senescence by stabilizing the methyltransferase SET8 and transcriptionally repressing p21.
Su(var)3-9, Enhancer-of-zeste, and Trithorax (SET) domain-containing protein 8 (SET8) is the sole enzyme that monomethylates Lys-20 of histone H4 (H4K20). SET8 has been implicated in the regulation of multiple biological processes, such as gene transcription, the cell cycle, and senescence. SET8 quickly undergoes ubiquitination and degradation by several E3 ubiquitin ligases; however, the enzyme that deubiquitinates SET8 has not yet been identified. Here we demonstrated that ubiquitin-specific peptidase 17-like family member (USP17) deubiquitinates and therefore stabilizes the SET8 protein. We observed that USP17 interacts with SET8 and removes polyubiquitin chains from SET8. USP17 knockdown not only decreased SET8 protein levels and H4K20 monomethylation but also increased the levels of the cyclin-dependent kinase inhibitor p21. As a consequence, USP17 knockdown suppressed cell proliferation. We noted that USP17 was down-regulated in replicative senescence and that USP17 inhibition alone was sufficient to trigger cellular senescence. These results reveal a regulatory mechanism whereby USP17 prevents cellular senescence by removing ubiquitin marks from and stabilizing SET8 and transcriptionally repressing p21.


Traumatic brain injury and chronic pain: differential types and rates by head injury severity.
Traumatic brain injury has been associated with many physical and neurobehavioral consequences, including pain problems. Documented most has been the presence of posttraumatic headaches that are associated with the postconcussion syndrome. This study therefore examined types and rates of chronic pain problems in patients seen in an outpatient brain injury rehabilitation program. A total of 104 patients were evaluated, 66 of whom were male and 38 female, and the average time postinjury was 26 months. Headaches were the most frequent chronic pain problem across both mild and the moderate/severe groups, although in the former, a significantly higher frequency was noted (89%) when compared against the latter group. The same relative rates were seen for chronic neck/shoulder, back, and other pain problems. The mild group also showed a higher frequency of concurrent pain problems, whereas in the moderate/severe group only one patient had more than one chronic pain problem. Results also showed that in the mild group neck/shoulder accompanied headaches 47% of the time, and back pain coexisted with headaches 44% of the time. These results underscore the high frequency of chronic pain problems in the mild head injury population and implicate the need for avoiding the mislabeling of symptoms such attentional deficits or psychological distress as attributable only to head injury sequelae in those with coexisting chronic pain. Early identification and intervention of pain syndromes in the mild head-injury population is also suggested.


Characterization of baboon class I major histocompatibility molecules. Implications for baboon-to-human xenotransplantation.
Increasingly strong medical and political pressures are stimulating consideration of the transplantation of baboon organs and cells into humans. Critical to the success of these xenotransplants is management of the immune system such that graft rejection and, in the case of bone marrow transplantation, graft-versus-host disease do not result in transplant failure. The polymorphic products of the major histocompatibility complex (MHC) are the primary barrier to successful allotransplantation, and here we describe class I MHC molecules from baboon (Papio anubis) to gain an understanding of how similarities and differences between baboon and human MHC molecules might affect xenograft survival and function. Comparative analyses of our five novel baboon class I molecules with defined HLA class I molecules demonstrate that the baboon class I molecule are up to 90% identical. Disparity between baboon class I proteins and their human homologues lies predominately at positions in the antigen-binding groove, while C-terminal portions of the class I heavy chain are more conserved between the two species. Such concentration of cross-species differences within the alpha1 and alpha2 domains involves a majority of substitutions at positions demonstrating polymorphism in human alleles; the location of substitutions distinguishing baboon and human molecules thus resembles the positioning of human class I allopolymorphisms. Because this preliminary characterization indicates that both baboon and human T cells with be restricted by xenogeneic class I molecules, immune responses triggered during baboon-to-human transplantation should mimic those arising during MHC mismatched human allotransplantation.


Risk communication in the case of the Fukushima accident: Impact of communication and lessons to be learned.
Risk communication about the Fukushima Daiichi nuclear power plant accident in 2011 was often not transparent, timely, clear, nor factually correct. However, lessons related to risk communication have been identified and some of them are already addressed in national and international communication programmes and strategies. The Fukushima accident may be seen as a practice scenario for risk communication with important lessons to be learned. As a result of risk communication failures during the accident, the world is now better prepared for communication related to nuclear emergencies than it was 5 years ago The present study discusses the impact of communication, as applied during the Fukushima accident, and the main lessons learned. It then identifies pathways for transparent, timely, clear and factually correct communication to be developed, practiced and applied in nuclear emergency communication before, during, and after nuclear accidents. Integr Environ Assess Manag 2016;12:683-686. © 2016 SETAC.


Screening of a RAPD marker tightly linked to Co gene in apple and the SCAR marker conversion.
A DNA marker linked to the columnar gene (Co) in apple (Malus domestica) was explored based on the population of 105 progenies of 'Spur Fuji' x 'Telamon' by bulk segregant analysis (BSA) and Random Amplified Polymorphic DNA (RAPD) technique. A total of 300 random primers were screened and a RAPD marker (S1142(682)) closely linked to Co gene (2.86 cM) was identified and then sequenced. Four specific PCR primers (two forward primers and two reverse primers) were designed,and the products of SCAR-PCR indicated that all the four pairs of primers could amplify polymorphic bands between columnar and non-columnar traits, so any of them could serve as the specific SCAR primers. One pair of these specific primers was chosen to amplify each individual in the population, and the result showed that the co-segregation pattern of this SCAR marker and Co gene was the same as that of the RAPD marker. Furthermore, it was found that the nucleotide sequence of the RAPD marker fragment contained an open reading frame (ORF) that could encode 68 deduced amino acid residues at the position of +45 - +251.


Ribosome Fingerprinting with a Solid-State Nanopore.
Nanopores hold great potential for the analysis of complex biological molecules at the single-entity level. One particularly interesting macromolecular machine is the ribosome, responsible for translating mRNAs into proteins. In this study, we use a solid-state nanopore to fingerprint 80S ribosomes and polysomes from a human neuronal cell line andDrosophila melanogaster cultured cells and ovaries. Specifically, we show that the peak amplitude and dwell time characteristics of 80S ribosomes are distinct from polysomes and can be used to discriminate ribosomes from polysomes in mixed samples. Moreover, we are able to distinguish large polysomes, containing more than seven ribosomes, from those containing two to three ribosomes, and demonstrate a correlation between polysome size and peak amplitude. This study highlights the application of solid-state nanopores as a rapid analytical tool for the detection and characterization of ribosomal complexes.


Poly(Lactic Acid)/Graphite Nanoplatelet Nanocomposite Filaments for Ligament Scaffolds.
The anterior cruciate ligament (ACL) is one of the most prone to injury in the human body. Due to its insufficient vascularization and low regenerative capacity, surgery is often required when it is ruptured. Most of the current tissue engineering (TE) strategies are based on scaffolds produced with fibers due to the natural ligament's fibrous structure. In the present work, composite filaments based on poly(L-lactic acid) (PLA) reinforced with graphite nanoplatelets (PLA+EG) as received, chemically functionalized (PLA+f-EG), or functionalized and decorated with silver nanoparticles [PLA+((f-EG)+Ag)] were produced by melt mixing, ensuring good filler dispersion. These filaments were produced with diameters of 0.25 mm and 1.75 mm for textile-engineered and 3D-printed ligament scaffolds, respectively. The resulting composite filaments are thermally stable, and the incorporation of graphite increases the stiffness of the composites and decreases the electrical resistivity, as compared to PLA. None of the filaments suffered significant degradation after 27 days. The composite filaments were processed into 3D scaffolds with finely controlled dimensions and porosity by textile-engineered and additive fabrication techniques, demonstrating their potential for ligament TE applications.


Ventricular and myocardial efficiencies during acute aortic regurgitation in conscious dogs.
Alterations in cardiac efficiency may signal pathologic stresses and energetic adaptation during aortic regurgitation (AR). LV systolic function, left coronary blood flow, and AVO2 difference were measured in conscious dogs to assess LV and contractile efficiencies at baseline, 1 day (n=10), 1 week (n=10), and 3 weeks (n=8) of AR. LV systolic function was assessed by the preload recruitable stroke work relationship. Total LV Efficiency (TEFF=SWxHeart Rate/MVO2) and contractile efficiency (CEFF=1/the slope of the MVO2 -pressure-volume area relationship) and steady-state potential energy (PVA-SWxHR), mechanical coupling efficiency (MCE=SWxHR/PVA) were calculated. LV systolic function decreased by 17% at 1 day (P<.05) and by 24% at 3 weeks (P<.05). CEFF decreased from 58+/-8% to 38+/-10% (P<.05) at 1 day, normalized at 1 week, and decreased to 28+/-14% at 3 weeks (P<.05). TEFF was not altered at 1 day and 1 week but decreased by 3 weeks (P<.05). MCE trended downward from baseline of 47+/-5%, reaching significance at 3 weeks (34+/-6%, P<.05). CEFF decreases acutely, indicating diminished economy of myocardial contraction. CEFF normalizes at 1 week, suggesting adequate compensation. TEFF is not altered in early AR. By 3 weeks, LV systolic dysfunction is accompanied by depressed TEFF, mechanical coupling, and CEFF signaling the onset of decompensated AR. Thus, volume overload of acute AR resulted in early compensation at the expense of myocardial efficiency with subsequent global dysfunction characterized by depressed LV systolic mechanics, mechanical, coupling, and contractile efficiencies.


[The treatment of acute cholecystitis complicated by mechanical jaundice].
After analyzing the summed up treatment results in 368 patients with acute cholecystitis, complicated by obstructive jaundice, the inference is reached that it is a matter of a complication, unfavourable in terms of prognosis, with a definite impact on both immediate and long-term therapeutic results. Early operative intervention following intensive preoperative preparation (including ERHPG with endoscopic papillosphincterotomy and ensuing biliary decompression, or echographic percutaneous cholecystectomy) contribute to control the acute inflammatory process in the gallbladder, and preclude the development of liver (or hepato-renal) failure against the background of obstructive jaundice. Proceeding from the severe, irreversible changes in liver and kidney, hardly responding to treatment, and persisting deterioration of the general condition, acute cholecystitis complicated by obstructive jaundice is defined as an emergency life-endangering condition, requiring a priority operative approach.


Block of Nav1.8 by small molecules.
Sodium channels are key proteins in regulating neuronal excitability and accumulating data suggest that specific subtypes of voltage-dependent sodium channels are important in signaling various types of pain. Consistent with this theme, Jarvis et al.(7) recently reported the identification of a subtype-selective Na(v)1.8 blocker that was active in several pre-clinical models of pain. During the course of these studies compounds were also identified that showed large differences in potency when tested on Na(v)1.8 channels from different species. This addendum illustrates one of these compounds along with the potency correlation between recombinant and native tetrodotoxin-resistant sodium channels for additional examples. These data show that significant differences can be observed for sodium channel blockers across species and highlight the importance of considering this possibility when searching for new compounds and research tools to probe sodium channel function.


Methods for measuring performance of vehicle cab air cleaning systems against aerosols and vapours.
Vehicle cabs equipped with an effective air cleaning and pressurization system, fitted to agricultural and off-road machineries, isolate drivers from the polluted environment, in which they are likely to work. These cabs provide protection against particulate and gaseous pollutants generated by these types of work activities. Two laboratory methods have been applied to determining the performance characteristics of two cabs of different design, namely, optical counting-based measurement of a potassium chloride (KCl) aerosol and fluorescein aerosol-based tracing. Results of cab confinement efficiency measurements agreed closely for these two methods implemented in the study. Measurements showed that high confinement efficiencies can be achieved with cabs, which are properly designed in ventilation/cleaning/airtightness terms. We also noted the importance of filter mounting airtightness, in which the smallest defect is reflected by significant degradation in cab performance. Determination of clean airflow rate by monitoring the decrease in test aerosol concentration in the test chamber gave excellent results. This method could represent an attractive alternative to methods involving gas tracing or air velocity measurement at blowing inlets.


Domestic dog roaming patterns in remote northern Australian indigenous communities and implications for disease modelling.
Although Australia is canine rabies free, the Northern Peninsula Area (NPA), Queensland and other northern Australian communities are at risk of an incursion due to proximity to rabies infected islands of Indonesia and existing disease spread pathways. Northern Australia also has large populations of free-roaming domestic dogs, presenting a risk of rabies establishment and maintenance should an incursion occur. Agent-based rabies spread models are being used to predict potential outbreak size and identify effective control strategies to aid incursion preparedness. A key component of these models is knowledge of dog roaming patterns to inform contact rates. However, a comprehensive understanding of how dogs utilise their environment and the heterogeneity of their movements to estimate contact rates is lacking. Using a novel simulation approach - and GPS data collected from 21 free-roaming domestic dogs in the NPA in 2014 and 2016 - we characterised the roaming patterns within this dog population. Multiple subsets from each individual dog's GPS dataset were selected representing different monitoring durations and a utilisation distribution (UD) and derived core (50%) and extended (95%) home ranges (HR) were estimated for each duration. Three roaming patterns were identified, based on changes in mean HR over increased monitoring durations, supported by assessment of maps of daily UDs of each dog. Stay-at-home dogs consolidated their HR around their owner's residence, resulting in a decrease in mean HR (both core and extended) as monitoring duration increased (median peak core and extended HR 0.336 and 3.696ha, respectively). Roamer dogs consolidated their core HR but their extended HR increased with longer monitoring durations, suggesting that their roaming patterns based on place of residence were more variable (median peak core and extended HR 0.391 and 6.049ha, respectively). Explorer dogs demonstrated large variability in their roaming patterns, with both core and extended HR increasing as monitoring duration increased (median peak core and extended HR 0.650 and 9.520ha, respectively). These findings are likely driven by multiple factors that have not been further investigated within this study. Different roaming patterns suggest heterogeneous contact rates between dogs in this population. These findings will be incorporated into disease-spread modelling to more realistically represent roaming patterns and improve model predictions.


Characterization of lysosomal acid lipase by site-directed mutagenesis and heterologous expression.
Lysosomal acid lipase (LAL) is essential for the hydrolysis of cholesterol esters and triglycerides that are delivered to the lysosomes via the low density lipoprotein receptor system. The deficiency of LAL is associated with cholesteryl ester storage disease (CESD) and Wolman's disease (WD). We cloned the human LAL cDNA and expressed the active enzyme in the baculovirus system. Two molecular forms (M(r) approximately 41,000 and approximately 46,000) with different glycosylation were found intracellularly, and approximately 24% of the M(r) approximately 46,000 form was secreted into the medium. Tunicamycin treatment produced only an inactive M(r) approximately 41,000 form. This result implicates glycosylation occupancy in the proper folding for active-site function. Catalytic activity was greater toward cis- than trans-unsaturated fatty acid esters of 4-methylumbelliferone and toward esters with 7-carbon length acyl chains. LAL cleaved cholesterol esters and mono-, tri-, and diglycerides. Heparin had a biphasic effect on enzymatic activity with initial activation followed by inhibition. Inhibition of LAL activity by tetrahydrolipstatin and diethyl p-nitrophenyl phosphate suggested the presence of active serines in binding/catalytic domain(s) of the protein. Site-directed mutagenesis at two putative active centers, GXSXG, showed that Ser153 was important to catalytic activity, whereas Ser99 was not and neither was the catalytic nucleophile. Three reported mutations (L179P, L336P, and delta AG302 deletion) from CESD patients were created and expressed in the Sf9 cell system. None cleaved cholesterol esters, and L179P and L336P cleaved only triolein at approximately 4% of wild-type levels. These results suggest that mechanisms, in addition to LAL defects, may operate in the selective accumulation of cholesterol esters or triglycerides in CESD and WD patients.


Dental implants treatment outcomes in patient under active therapy with alendronate: 3-year follow-up results of a multicenter prospective observational study.
To evaluate the 3-year clinical and radiographic data of fixed implant-supported dental prosthesis delivered to patients having taken alendronate 35-70 mg weekly for at least 3 years before implant placement. Forty consecutive patients treated with oral bisphosphonates and requiring an implant-supported restoration were recruited in two private centers between January 2008 and December 2011. Implants were inserted through minimally invasive approach under antibacterial and antibiotic treatment, 6 months after alendronate administration stopping. After 4 months of submerged healing, implants underwent prosthetic loading. Hygiene maintenance and clinical assessments were scheduled every 4 months for 3 years. Outcome measures were the following: implant and prosthetic success, survival rates, any observed clinical complications, marginal bone remodeling, probing pocket depth and bleeding-on-probing. At the end of the study, eight patients dropped out. The final sample size resulted in 32 consecutive partially or fully edentulous patients (32 females; mean age 64.6 years) with 98 submerged implants. In only one patient, maxillary implant failed during healing period. No prosthesis failed during the entire follow-up, and no major complications were recorded. Implant and prostheses success resulted in an overall survival rate of 98, 98% and 100%, respectively. Three-year mean marginal bone loss was 1.35 ± 0.21 (CI 95% 1.24-1.38). Successful soft tissue parameters were found around all implants. Oral bisphosphonate therapy did not appear to significantly affect implant survival and success in case of accurate treatment time selection, minimally invasive surgical approach and constant follow-up. Further prospective studies involving larger sample sizes and longer durations of follow-up are required to confirm these results.


Chalcone inhibits the proliferation of human breast cancer cell by blocking cell cycle progression and inducing apoptosis.
Chalcones are discussed to represent cancer preventive food components in a human diet that is rich in fruits and vegetables. In this study, we examined chalcone (1,3-diphenyl-2-propenone) for its effect on proliferation in human breast cancer cell lines, MCF-7 and MDA-MB-231. The results showed that chalcone inhibited the proliferation of MCF-7 and MDA-MB-231 by inducing apoptosis and blocking cell cycle progression in the G2/M phase. Immunoblot assay showed that chalcone significantly decreased the expression of cyclin B1, cyclin A and Cdc2 protein, as well as increased the expression of p21 and p27 in a p53-independent manner, contributing to cell cycle arrest. An enhancement in Fas/APO-1 and its two form ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), was responsible for the apoptotic effect induced by chalcone. In addition, chalcone also triggered the mitochondrial apoptotic signaling by increasing the amount of Bax and Bak and reducing the level of Bcl-2 and Bcl-X(L), and subsequently activated caspase-9 in MCF-7 and MDA-MB-231 cells. Taken together, our study suggests that the blockade of cell cycle progression and initiation of cell apoptotic system may participate in the antiproliferative activity of chalcone in human breast cancer cells.


[Administration of low-dose heparin in total nutrient admixture prevents central venous catheter-related infections in neonates].
Peripherally inserted central catheter (PICC) is widely used to provide a long-term access for the administration of total parenteral nutrition and medications. Catheter-related infections (CRI) are common complications of PICC. The purpose of this retrospective study was to investigate the role of low-dose heparin added to the total nutrient admixture (CTNA) in the prevention of CRI. Eighty-three neonates who underwent PICC received TNA with (heparin group, n=43) or without heparin (0.5 U/mL) (control group, n=40). The incidence of CRI was compared between the two groups. The incidences of catheter obstruction (5% vs 20%) and the catheter-tip colonization (2% vs 18%) in the heparin group were significantly lower than those in the control group (p<0.05). None of the neonates in the heparin group had clinical evidence of catheter-related bloodstream infection, but 5 cases in the control group (p<0.05). The administration of low-dose heparin in TNA may decrease the incidences of catheter obstruction and CRI.


High-risk groups and screening strategies for early detection of hepatocellular carcinoma in patients with chronic liver disease.
Characteristics of high-risk groups for hepatocellular carcinoma (HCC) in Japan were studied to establish screening strategies for early detection of the tumor. Some 93% of patients with HCC were associated with chronic liver disease. On the other hand, 67% of patients with liver cirrhosis had HCC at autopsy. Most were related to current hepatitis virus infection. An analysis of risk factors among 120 patients with chronic hepatitis revealed that age and histological findings were independent risk factors, while HBsAg, anti-HCV, sex, history of heavy drinking, history of blood transfusion were not independent risk factors. Multivariate analysis of 239 patients with liver cirrhosis demonstrated that age, positivity for HBsAg and/or anti-HCV, family history of liver disease, hepatic reserve, and a history of radical resection were independent factors related to the development of HCC. A screening schedule for cirrhotic patients was established in accordance with these results; ultrasonography was done every three months, and tumor markers measured every two months. The screening strategy proved to be effective for the early detection of HCC and improvement of the prognosis.


[Periodontal disease--an additional risk factor for cardiovascular diseases?].
In 1989, a case-control study was published, linking between coronary heart disease and periodontal disease in the studied population. Since then, a number of additional studies, focused the attention to the possible role of dental infections in the pathogenesis of atherosclerosis. Some of these newer cohort studies, are prospective in nature, measuring incidence of the two diseases in large patient populations. The present article reviews these studies, and the proposed mechanisms which might explain the relationships between these two systemically distinct diseases.


Helicoductus thulakoceras n. g., n. sp. (Cestoda: Hymenolepididae) a parasite of Charadrius marginatus (Aves: Charadrii) from South Africa.
The authors describe and illustrate Helicoductus thulakoceras n. g., n. sp., a parasite of Charadrius marginatus (Aves: Charadrii) from South Africa. This hymenolepidid cestode is 1.5-3 mm long, with a rostellum armed with 10 diorchoid hooks 75-80 microm long (mean 77 microm) and anomalous terminal genital ducts. One spine (10-15 microm long) is inserted at the ventral extremity of the male genital pouch. An invaginated cirrus is absent. A non-retractable and non-invaginable external tube, 25-30 x 4-2.5 microm, appears as a spiral, sclerotinised, spinous canal, which is non-retractable, non-invaginable and directed dorso-ventrally from the genital pouch to a second ventral canal parallel with the male genital pouch; the second canal is thin and spine-like (15-20 x 1.5 microm) with a thick hyaline muff. These peculiar anatomical structures are discussed. They are considered to justify the erection of a new genus.


A Model for the Propagation of Action Potentials in Non-Uniformly Excitable Media.
Electrophysiological properties of cardiac tissue change as a function of position. We define the "excitability" as the propagation velocity of an excitation pulse through the tissue, and study a simple FitzHugh-Nagumo (FHN) model of heart tissue whose excitability changes with position. The propagation velocity is shown to be a good continuous measure of the excitability for both limit cycle and excitable tissue. The influence of the spatial dependence of the excitability is examined for several normal and pathological situations. A novel transient effect is observed for a train of pulses propagating across an excitability step. Copyright 1999 Academic Press.


Steroids inhibit nicotinic acetylcholine receptors.
Application of progesterone to Xenopus oocytes expressing a cloned neuronal nicotinic acetylcholine (nAChR) revealed two effects. The first effect was a fully reversible reduction of the current induced by acetylcholine (ACh), its onset being nearly instantaneous. The second effect, which developed in a few hours, was an irreversible suppression of ACh-evoked currents. The transient inhibition had an apparent Ki of 7 microM when tested with 50 nM ACh, but the percentage of inhibition was positively correlated to the ACh concentration. A reduction of ACh-induced currents which appeared immediately upon progesterone application was also observed with muscle nAChR expressed in oocytes and with nAChR on membrane patches isolated from ciliary ganglion neurons. Thus nAChRs are modulated by progesterone and steroids may play an important role in nicotinic cholinoception.


Establishing risk factors and outcomes for congenital hypothyroidism with gland in situ using population-based data linkage methods: study protocol.
There has been an increase in the birth prevalence of congenital hypothyroidism (CH) since the introduction of newborn screening, both globally and in the UK. This increase can be accounted for by an increase in CH with gland in situ (CH-GIS). It is not known why CH-GIS is becoming more common, nor how it affects the health, development and learning of children over the long term. Our study will use linked administrative health, education and clinical data to determine risk factors for CH-GIS and describe long-term health and education outcomes for affected children. We will construct a birth cohort study based on linked, administrative data to determine what factors have contributed to the increase in the birth prevalence of CH-GIS in the UK. We will also set up a follow-up study of cases and controls to determine the health and education outcomes of children with and without CH-GIS. We will use logistic/multinomial regression models to establish risk factors for CH-GIS. Changes in the prevalence of risk factors over time will help to explain the increase in birth prevalence of CH-GIS. Multivariable generalised linear models or Cox proportional hazards regression models will be used to assess the association between type of CH and school performance or health outcomes. This study has been approved by the London Queen Square Research Ethics Committee and the Health Research Authority's Confidentiality Advisory Group CAG. Approvals are also being sought from each data provider. Obtaining approvals from CAG, data providers and information governance bodies have caused considerable delays to the project. Our methods and findings will be published in peer-reviewed journals and presented at academic conferences.


Primary invasive breast carcinoma in Oslo 1980-1989. Incidence and delay.
A retrospective review was performed on 2704 consecutive patients in Oslo in whom histologically or cytologically confirmed primary invasive breast carcinoma had been diagnosed between 1980 and 1989. The age-adjusted incidence rates were significantly higher in the city of Oslo compared with those of the whole country and remained unchanged during the study period. The percentage of patients who could be treated radically remained unchanged. Among the patients with radical treatment the distribution of pT category and stage was similar during the first and last years. The median delay (from onset of symptoms to start of treatment) of two months remained unchanged during the decade and was not related to patient's age, histological grade or tumour localization in the quadrants of the breast. With increasing duration of delay the number of patients not suitable for radical treatment increased. When considering all 2704 patients, the radicality of treatment, the patient's age and delay were correlated with tumour-specific survival and remained independent factors of tumour-specific survival in the multivariate analysis. The unchanged distribution of pT category and stage in the radically treated patients during the decade surveyed is most probably related to the lack of screening mammography in Norway.


Strengths and limitations of International Classification of Disease Ninth Revision Clinical Modification codes in defining cervical spine surgery.
Retrospective study. To evaluate the sensitivity and specificity of International Classification of Disease Ninth Revision Clinical Modification (ICD9-CM) hospital discharge codes to define degenerative cervical spine surgery in comparison to patient operative notes in the medical record. Population-based studies of spine surgery have often relied on administrative databases as a primary information source, but little is known about the validity of using ICD9-CM codes to identify these operations. We performed a retrospective study comparing ICD9-CM billing codes to patient operative notes, the gold standard, for patients undergoing spine surgery in 2006 at a single academic center. We identified 1090 procedures of which 265 were categorized as cervical spine surgery for degenerative indications based on the operative notes. Compared to operative notes, our ICD9-CM algorithm had high sensitivity and specificity for selecting surgery at the cervical spine level and cervical spine surgery for degenerative indications. Categorization of cases by procedure had high sensitivity and specificity for fusion and surgical approach (>95%). Categorization of cases by primary diagnosis was generally less accurate. Cervical spondylosis with myelopathy was the most sensitive primary diagnosis. Categorization of cases by procedure had high sensitivity and specificity for fusion and surgical approach (≥96%). However, diagnoses such as herniated disc and procedures such as laminectomy had low sensitivity but high specificity. The use of our ICD9-CM algorithm to define spine surgery at the cervical spine level, and degenerative cervical spine surgery is highly accurate. Although specific diagnoses codes are mostly insensitive, an ICD9-CM algorithm can be used to study these procedures with reasonable precision.


Updates: Routine screening for antibodies to HIV-1, civilian applicants for U.S. military service and U.S. Armed Forces, active and reserve components.
During routine testing of civilian applicants for U.S. military service, the overall seroprevalence of antibodies to HIV-1 was lower in 2010 than in any year since 1990. Among members of the active components of the U.S. Army and Air Force, HIV-1 seroprevalences were higher in 2008-2010 than in recent prior years. Among members of the active components of the U.S. Navy and Marine Corps, the Marine Corps Reserve, and the Army National Guard, HIV-1 seroprevalences have slightly declined or remained relatively stable for at least ten years. In the reserve components of most of the service branches, it is difficult to discern long-term trends because of instability of seroprevalences observed in the relatively small numbers of reserve component members tested each year.


Burden of invasive pneumococcal disease in children in Casablanca, Morocco four years after the introduction of pneumococcal vaccination.
Streptococcus pneumonia is a common bacterium that can cause several types of infections, including invasive infections especially in children aged <5 years. The aim of this work is to report the different aspects of invasive pneumococcal disease (IPD) in a pediatric hospital in Casablanca, Morocco 4 years after the implementation of pneumococcal vaccination. We conducted a descriptive, retrospective study over a 4-year period from January 2015 to December 2018 in A. Harouchi Pediatric Hospital in Casablanca. This study included hospitalized children aged 0 to 14 years´ old who had an IPD. The data was collected using a data collection sheet from archived patient records and computerized laboratory database; organization of data was done using Microsoft Excel 2016 and analysis was done using SPSS-20. A total of 68 patients were included in this series over the 4-year period. Meningitis was the most common IPD (54.41%) followed by bacteremia (19.17%) and then pneumonia (16.17%). Of the 35 serogrouped strains, 7 were included in the pneumococcal conjugate vaccine (PCV) 10 (20%), 6 were PCV13-nonPCV10 serotypes (17.14%) and 6 were non-vaccine serotypes (17.14%). Among the strains tested for their antibiotic resistance profile, 32.70% were resistant to penicillin, tetracycline (29.78%), erythromycin (20.75%) and cotrimoxazole (17.31%). One strain was intermediate to ceftriaxone. The evolution was unfavorable for 18 patients (26.47%). This study reported high resistance rates to penicillin, tetracyclin and erythromycin. The mortality essentially concerned meningitis patients. Ongoing surveillance of antibiotic susceptibility and serotype distribution is needed by a national surveillance network.


Successful treatment of lymphomatoid papulosis with photodynamic therapy.
A 40-year-old woman presented with a prolonged history of recurrent crops of erythematous papules and nodules on her abdomen, arms and legs. Histological examination of a cutaneous biopsy revealed Type A lymphomatoid papulosis. Over a 3-year period, some of the patient's lesions had proven to be resistant to treatment with topical and intralesional corticosteroids and systemic agents including methotrexate, tetracycline and nicotinamide. These resistant lesions were treated with two sessions of methyl aminolevulinate photodynamic therapy given 1 week apart. Review 11 months post-photodynamic therapy demonstrated complete clinical clearance at the treatment site. While photodynamic therapy is considered a standard non-surgical treatment option for non-melanoma skin cancers and has been described in a number of non-oncological indications, this is the first report of its use in lymphomatoid papulosis.


Transcription of sea urchin histone genes in Escherichia coli.
DNA fragments comprising units of the repeated histone genes form the sea urchins Psammechinus miliaris and Echinus esculentus were placed under the control of bacteriophage Lambda promoters by cloning into lambda replacement vectors. Although promoter-like regions exist within the cloned fragments, transcription of the histone genes is controlled mainly, but not exclusively, by lambda PL promoter. A transcription map of the cloned P. miliaris histone DNA fragment was obtained. The order of histone genes in E. esculentus was deduced from electron microscopic analyses of heteroduplexes with P. miliaris histone genes, and is similar to that in P. miliaris. Translation products of the transcripts have not been found in E. coli.


Perioperative outcomes and cosmesis analysis of patients undergoing laparoendoscopic single-site adrenalectomy: a comparison of transumbilical, transperitoneal subcostal, and retroperitoneal subcostal approaches.
To compare the perioperative outcomes and cosmetic results for transumbilical (TU), transperitoneal subcostal (TS), and retroperitoneal subcostal (RS) laparoendoscopic single-site surgery (LESS) adrenalectomy (AD). An observational study was conducted of patients who were had undergone LESS-AD using a TU (n = 9), TS (n = 17), or RS (n = 16) approach. The perioperative outcomes and comprehensive cosmetic results were analyzed statistically. The RS-LESS-AD patients were more likely to have an indication for surgery of a right adrenal mass (TU-LESS-AD 11.1% and TS-LESS-AD 5.9% vs RS-LESS-AD 43.8%, P = .016) or partial AD (0% vs 9% vs 87.5%, P < .001). The TU-LESS-AD procedures had a longer median operative time but significantly lower postoperative pain. The median cosmesis rating for the TU-LESS-AD, TS-LESS-AD, and RS-LESS-AD scar photographs was 10, 8, and 9, respectively (P = .010). Only the cosmesis ratings after the photograph viewing were statistically significant across the surgical approaches (9.5 vs 8 vs 9, P = .048). Assuming equivalent surgical complication risks across the approaches, the preference for future TU-LESS-AD, TS-LESS-AD, RS-LESS-AD was 86%, 6%, and 8%, respectively. As the theoretical risk of TU-LESS-AD increased, the preference for TU-LESS-AD decreased and the preference for TS-LESS-AD and RS-LESS-AD increased. LESS-AD is an effective procedure with a high level of cosmesis using a TU, TS, or RS approach. The surgeon's background, patient characteristics, and cosmetic perception must be carefully considered as a part of the entire clinical picture so that LESS-AD can be used for patients who will derive the most benefit.


Higher-order generalized hydrodynamics: Foundations within a nonequilibrium statistical ensemble formalism.
Construction, in the framework of a nonequilibrium statistical ensemble formalism, of a higher-order generalized hydrodynamics, also referred to as mesoscopic hydrothermodynamics, that is, covering phenomena involving motion of fluids displaying variations short in space and fast in time-unrestricted values of Knudsen numbers, is presented. In that way, an approach is provided enabling the coupling and simultaneous treatment of the kinetics and hydrodynamic levels of descriptions. It is based on a complete thermostatistical approach in terms of the densities of matter and energy and their fluxes of all orders covering systems arbitrarily driven away from equilibrium. The set of coupled nonlinear integrodifferential hydrodynamic equations is derived. They are the evolution equations of the Gradlike moments of all orders, derived from a generalized kinetic equation built in the framework of the nonequilibrium statistical ensemble formalism. For illustration, the case of a system of particles embedded in a fluid acting as a thermal bath is fully described. The resulting enormous set of coupled evolution equations is of unmanageable proportions, thus requiring in practice to introduce an appropriate description using the smallest possible number of variables. We have obtained a hierarchy of Maxwell times, associated to the set of all the higher-order fluxes, which have a particular relevance in the process of providing criteria for establishing the contraction of description.


Cooking a Research Project: New Trends in the Kitchen and in Scientific Policies.
The culture of chefs from the world's best restaurants is substituted by new trends paradigmatically epitomized by the TV program Masterchef. The authors feel that a similar transformation affects modern research. Recent scientific policies constrict the design of research grants with the aim of short-term maximization of the monetary value generated by the researcher.


The Candida glabrata Amt1 copper-sensing transcription factor requires Swi/Snf and Gcn5 at a critical step in copper detoxification.
The yeast Candida glabrata rapidly autoactivates transcription of the AMT1 gene in response to potentially toxic copper levels through the copper-inducible binding of the Amt1 transcription factor to a metal response element (MRE) within a positioned nucleosome. Our previous studies have characterized the role of a 16 bp homopolymeric dA:dT DNA structural element in facilitating rapid Amt1 access to the AMT1 promoter nucleosomal MRE. In this study, we have used the genetically more facile yeast Saccharomyces cerevisiae to identify additional cellular factors that are important for promoting rapid autoactivation of the AMT1 gene in response to toxic copper levels. We demonstrate that the Swi/Snf nucleosome remodelling complex and the histone acetyltransferase Gcn5 are both essential for AMT1 gene autoregulation, and that the requirement for these chromatin remodelling factors is target gene specific. Chromatin accessibility measurements performed in vitro and in vivo indicate that part of the absolute requirement for these factors is derived from their involvement in facilitating nucleosomal access to the AMT1 promoter MRE. Additionally, these data implicate the involvement of Swi/Snf and Gcn5 at multiple levels of AMT1 gene autoregulation.


Ligand-stimulated signaling events in immature CD4+CD8+ thymocytes expressing competent T-cell receptor complexes.
During thymic selection of the developing T-cell repertoire, the fate of individual CD4+CD8+ thymocytes is determined by the specificity of the T-cell antigen receptors (TCRs) they express. Paradoxically, most CD4+CD8+ thymocytes express few TCR molecules, and those they express are essentially incapable of transducing intracellular signals as measured by intracellular calcium mobilization. However, both TCR number and calcium-signaling capability are significantly induced in CD4+CD8+ thymocytes when the cells are released from intrathymic inhibitory signals that are mediated by their CD4 molecules. Here, the response to ligand engagement of TCR on "induced" CD4+CD8+ thymocytes that have been released from CD4-mediated inhibition was examined and was found to result in internalization of surface TCR complexes and rephosphorylation of zeta chains of the TCR complex. In addition, a proportion of induced CD4+CD8+ thymocytes were found to fragment their DNA upon ligand engagement. Thus, this study describes early events in immature CD4+CD8+ thymocytes resulting from TCR-mediated signals.


The perinephric space and renal fascia: review of normal anatomy, pathology, and pathways of disease spread.
The perinephric space is a cone-shaped retroperitoneal compartment containing the kidney, adrenal gland, perinephric fat, fibrous bridging septa, and a rich network of perirenal vessel and lymphatics. Perinephric space pathology may originate from within or outside the confines of the perirenal fascia. Most intrinsic perinephric space disease arises from the kidney or adrenal gland, and secondarily involves the perinephric space. Disease originating outside the cone of renal fascia may spread to the perinephric space via lymphatics (i.e., metastatic spread) or by directly transgressing perirenal fascial planes (e.g., invasive tumor or infections). Additionally, infiltrating soft tissue or rapidly accumulating retroperitoneal fluid may travel into or out of the perinephric space via perinephric bridging septa and renal fascia. In this article, we review the normal anatomy of the perinephric space and renal fascia, emphasizing the significance of retroperitoneal interfascial planes and perinephric bridging septa as a potential conduit for retroperitoneal disease spread. This review of normal anatomy and pathways of disease spread serves as background for a discussion of a variety of specific pathologic conditions that may involve the perinephric space and retroperitoneal fascia, including pancreatitis, retroperitoneal hematoma, urinoma, metastatic disease, and perirenal varices.


Concentration Gradients of trans-Zeatin Riboside and trans-Zeatin in the Maize Stem: Measurement by a Specific Enzyme Immunoassay.
A sensitive, specific enzyme immunoassay (EIA) for trans-zeatin riboside (ZR) and trans-zeatin (Z) in the 0.3 to 30 picomole range has been described. The reliability of the method for measuring ZR + Z in partially purified extracts of Zea mays L. tissues was verified by highperformance liquid chromatography. EIA measurements showed that there was a concentration gradient of ZR + Z along the length of the Zea stem. The topmost internodes, internodes 7 and 8 counting from the coleoptilar node, had the highest concentration ( approximately 130 picomoles per gram fresh weight). Moving basipetally, the concentration dropped approximately 10-fold to a minimum at internode 4, and then increased slightly in internodes 2 and 3. There were also gradients within each internode. The five lowest internodes contained the highest concentrations toward their apical end, the region which included the node; this asymmetry was less pronounced near the top of the plant.


Foreign transcriptional enhancers in yeast. II. Interplay of the polyomavirus transcriptional enhancer and Saccharomyces cerevisiae promoter elements.
In this paper, to further analyze the function of the polyoma enhancer in Saccharomyces cerevisiae, we use as reporter-genes derivatives of the yeast HIS3 gene flanked by two types of partially deleted promoters: in one, UAS elements are removed by deletion of sequences upstream of nt -80 (pGM3181) in the second both TATA boxes and UAS elements are removed by deletion of sequences upstream of nt -35 (pGM2809). These constructs have been studied both as free plasmids and after integration at the TRP1 chromosomal locus. We find that in general the polyoma holoenhancer (A + B domains) elicits transcription from the physiological HIS3 RNA start sites when the native TATA boxes are present. In contrast, an altered enhancer B-domain from polyoma mutant Py-B78, although active when inserted downstream of the test-gene or when coupled to a pseudopromoter (Ciaramella et al, accompanying manuscript), does not work properly in concert with the native yeast TATA boxes. We describe experiments that suggest an important role for the foreign enhancer in RNA start-site selection in yeast.


Expression of constitutively activated human c-Kit in Myb transformed early myeloid cells leads to factor independence, histiocytic differentiation, and tumorigenicity.
The cDNAs encoding wild type (WT) human receptor tyrosine kinase c-Kit and a constitutively activated mutant, V816Kit, were introduced into granulocyte-macrophage colony-stimulating factor (GM-CSF )-dependent early murine hemopoietic cells, which had been transformed with activated Myb. WTKit cells were able to grow in the presence of the human ligand for Kit, stem cell factor (SCF ), but displayed reduced growth and clonogenic potential in either SCF or GM-CSF compared with the parental cells in GM-CSF. In contrast, V816Kit cells grew without factor at a higher rate than the parental cells in GM-CSF and displayed increased clonogenicity. Dissection of the growth characteristics in liquid culture showed that in the presence of appropriate factors, the different populations had similar proliferation rates, but that V816Kit profoundly increased cell survival compared with WTKit or parental cells. This suggests that the signals transduced by WTKit activated with SCF, and by V816Kit, were not identical. Also, WTKit and V816Kit-expressing cells both varied from the early myeloid progenitor phenotype of the parental cells and gave rise to a small number of large to giant adherent cells that expressed macrophage (alpha-naphthyl acetate) esterase and neutrophil (naphtol-AS-D-chloroacetate) esterase, were highly phagocytic and phenotypically resembled histiocytes. Thus, WTKit activated by SCF and V816Kit were able to induce differentiation in a proportion of Myb-transformed myeloid cells. The factor independent V816Kit cells, unlike the parental and WTKit expressing cells, were shown to produce tumors of highly mitotic, invasive cells at various stages of differentiation in syngeneic mice. These results imply that constitutively activated Kit can promote the development of differentiated myeloid tumors and that its oncogenic effects are not restricted to lineages (mast cell and B-cell acute lymphoblastic leukemia), which have been reported previously. Furthermore, the mixed populations of cells in culture and in the tumors phenotypically resembled the leukemic cells from patients with monocytic leukemia with histiocytic differentiation (acute myeloid leukemia-M5c), a newly proposed subtype of myeloid leukemia.


Water-vapor absorption line measurements in the 940-nm band by using a Raman-shifted dye laser.
We report water-vapor absorption line measurements that are made by using the first Stokes radiation (930-982 nm) with HWHM 0.015 cm(-1) generated by a narrow-linewidth, tunable dye laser. Forty-five absorption line strengths are measured with an uncertainty of 6% and among them are fourteen strong lines that are compared with previous measurements for the assessment of spectral purity of the light source. Thirty air-broadened linewidths are measured with 8% uncertainty at ambient atmospheric pressure with an average of 0.101 cm(-1). The lines are selected for the purpose of temperature-sensitive or temperature-insensitive lidar measurements. Results for these line strengths and linewidths are corrected for broadband radiation and finite laser linewidth (0.015 cm(-1) HWHM) broadening effects and compared with the high-resolution transmission molecular absorption.


[Severe traumatic braininjury in children and adolescents].
Present a critical review of traumatic brain injury (TBI) in children and adolescents, focusing on severe TBI, the mortality and the factors related with poor outcome. It was made a systematic review in MEDLINE, SciElo e Lilacs, with the key words: traumatic brain injury, craniocerebral trauma, children and mortality. The most important articles related in the Guidelines of Brain Trauma Foundation (2000 e 2003) were selected too. TBI is one of the most important causes of mortality and morbidity in children and adolescents, and morbidity in children and adolescents. The mortality variation was between 10% and 55%, depending of the patients select criteria, trauma severity and units where the studies were made. The children mortality was, in general, lower than that found in adults and the most important factors related with an increased mortality were: Glasgow Coma Score, hypotension, cerebral swelling and lower cerebral perfusion press. Severe TBI endpoint treatment is to correct the secondary brain lesions related factors. The factors related with better outcomes in children with severe TBI are still obscures, despite the large number of studies, large numbers of studies. Many of these factors can be avoided or correct by aggressive fluid resuscitation, surgery treatment, monitoration and adequate intensive care.


Pattern formation of spiral waves in an inhomogeneous medium with small-world connections.
Pattern formation of spiral waves in an inhomogeneous excitable medium with small-world connections is investigated. In both cases, with completely local regular connections and with completely random connections, spiral waves cannot survive in the given inhomogeneous medium. It is found that with small-world connections (basically local connections plus a small number of random connections) a well behaved spiral wave can be formed against the destructive role of the inhomogeneous medium. There also exists an optimal fraction of random connections which can greatly enhance the probability of spiral wave formation; this resembles the behavior of stochastic resonance.


[Characteristics of Bacterial Community Structure in Wuliangsu Lake During an Irrigation Interval in Hetao Plain].
In order to study the bacterial community composition and corresponding function in Wuliangsu Lake at the end of the Hetao Plain during the irrigation gap period, lake samples were collected in September 2020, and the pH, TN, TP, DIP, DTP, NH4+-N, Chla, EC, SAL, and other indicators were analyzed. The 16S rRNA high-throughput sequencing method was used to explore the attached bacteria and bacterioplankton in 15 samples of the surface water in Wuliangsu Lake. The experimental results showed that:① the alpha diversity Chao and Shannon indices of attached bacteria were greater than that of bacterioplankton, but the median of Shannoneven index was the same. ② In each sampling point, the bacterioplankton of Proteobacteria and Actinobacteria in the top five dominant bacteria phyla were higher than that of attached bacteria, and the abundance of attached bacteria and bacterioplankton of Bacteroidota were staggered. On the contrary, the contents of attached bacteria of Verrucomicrobiota and Cyanobacteria were all higher than that of bacterioplankton. ③ Redundant analysis showed that pH had the most significant effect on dominant attached bacteria, and the effect of conductivity and salinity in dominant bacterioplankton was the most significant. ④ PICRUSt2 function prediction analysis showed that attached bacteria and planktonic bacteria had the strongest metabolic functions, showing abundant metabolic functions. There were 29 nitrogen-related effective KOs and 88 phosphorus-related effective KOs, with the greatest nitrogen-fixing function and strong inorganic phosphorus-dissolving function, and bacterioplankton played a greater role in the two functions.


Damage of tracer erythropoietin results in erroneous estimation of concentration in mouse submaxillary gland.
It has been previously reported that 1) plasma erythropoietin (Epo) titer during exposure to hypobaria is lower in nephrectomized rats and mice whose submaxillary glands (SMG) were either ablated or atrophied than in nephrectomized controls whose SMG were intact and 2) that the gland shows one of the highest levels of immunoreactive Epo (iEpo) in the body. The latter observation, however, was questioned recently when it was observed that SMG extracts degrade labeled Epo used as tracer antigen in the radioimmunoassay (RIA), thus giving invalid estimates of Epo. Since this interpretation was in turn questioned, the present study was conducted to obtain more information on the subject and make these conflicting points clear. Investigation of the reported/possible degradation of Epo by SMG homogenates was conducted via polyacrylamide gel electrophoresis followed by radioautography or by a RIA in solid phase in which there was no simultaneous incubation of the tracer antigen with the SMG homogenates. It was observed that 125I-labeled rhEpo was degraded when incubated with SMG homogenates. Degradation was rapid, being evident when incubation lasted 30 minutes, and occurred in the presence of a protease inhibitor. It showed a high degree of specificity since it did not occur when Epo was incubated with kidney homogenate or normal mouse serum. SMG homogenate did not degrade labeled thyrotrophic hormone and degraded alpha interferon (IFN-alpha) only partially. When estimates of iEpo in SMG homogenate were performed in conditions of simultaneous (SI-RIA) or nonsimultaneous (NSI-RIA) incubation of the homogenate with tracer Epo, it was observed that while estimates of Epo in plasma were similar in both types of RIA and somewhat higher in kidney homogenate in the SI-RIA than in the NSI-RIA, estimates of Epo in SMG were about 60 times higher in the former than in the latter. Therefore, it could be concluded that most of the Epo detected by standard RIA in SMG homogenate does not represent true Epo because of damage of tracer Epo which determines loss of the integrity of the RIA system.


Clinical update on the use of ospemifene in the treatment of severe symptomatic vulvar and vaginal atrophy.
The physiological decrease in vaginal estrogens is accountable for the emergence of vulvar and vaginal atrophy (VVA) and its related symptoms such as vaginal dryness, dyspareunia, vaginal and/or vulvar irritation or itching, and dysuria. The repercussion of these symptoms on quality of life often makes it necessary to initiate treatment. Up until now, the treatments available included vaginal moisturizers and lubricants, local estrogens, and hormonal therapy. However, therapeutic options have now been increased with the approval of 60 mg ospemifene, the first nonhormonal oral treatment with an agonist effect on the vaginal epithelium and an endometrial and breast safety profile which makes it unique. This is the first selective estrogen receptor modulator indicated in women with moderate-to-severe vaginal atrophy not eligible for local estrogen treatment. Considering that "local estrogen noneligible women" are those in whom such treatment cannot be administered either because it is contraindicated or due to skill issues, who are averse to the mode and convenience of vaginal products' administration or to their use on account of potential systemic absorption, or those who demonstrate dissatisfaction in terms of efficacy and safety, it is clear that there is a significant unmet medical need in VVA management. In fact, a great number of women show lack of adherence, dropping out of at least one VVA treatment, including nonhormonal moisturizers and lubricants, which they consider to be ineffective and uncomfortable. If they could choose, many of them may opt for oral treatment. In Phase III studies, ospemifene demonstrated efficacy in vaginal dryness and dyspareunia, regenerating vaginal cells, improving lubrication, and reducing pain during sexual intercourse. Symptoms improved in the first 4 weeks and endured for up to 1 year. Additionally, it demonstrated a good endometrial, cardiovascular system, and breast safety profile.


Recursive algorithm for arrays of generalized Bessel functions: Numerical access to Dirac-Volkov solutions.
In the relativistic and the nonrelativistic theoretical treatment of moderate and high-power laser-matter interaction, the generalized Bessel function occurs naturally when a Schrödinger-Volkov and Dirac-Volkov solution is expanded into plane waves. For the evaluation of cross sections of quantum electrodynamic processes in a linearly polarized laser field, it is often necessary to evaluate large arrays of generalized Bessel functions, of arbitrary index but with fixed arguments. We show that the generalized Bessel function can be evaluated, in a numerically stable way, by utilizing a recurrence relation and a normalization condition only, without having to compute any initial value. We demonstrate the utility of the method by illustrating the quantum-classical correspondence of the Dirac-Volkov solutions via numerical calculations.


Mnemonic firing of neurons in the monkey temporal pole during a visual recognition memory task.
1. We examined single-neuronal activity in the temporal pole of monkeys, including the anterior ventromedial temporal (VMT) cortex (the temporopolar cortex, area 36, area 35, and the entorhinal cortex) and the anterior inferotemporal (IT) cortex, during a visual recognition memory task. In the task, a trial began when the monkey pressed a lever. After a waiting period, a visual sample stimulus (S) was presented one to four times on a monitor with an interstimulus delay. Thereafter, a new stimulus (R) was presented. The monkeys were trained to remember S during the delay period and to release the lever in response to R. Colored photographs of natural objects were used as visual stimuli. 2. About 70% of the recorded neurons (225 of 311) responded to at least one of the Ss tested. Thirty percent of these neurons (68 of 225) continued to fire during the subsequent delay periods. In 75% of these neurons (51 of 68), the firing during the delay period strongly correlated with the response to S. 3. The discharge rate during the delay period did not correlate with the monkey's eye movements, pressing or releasing of the lever, or the reaction time. 4. If the monkey erroneously released the lever in response to S or during the delay period, the firing disappeared after the erroneous lever release. If the monkey failed to release the lever in response to R, the firing persisted even after R was withdrawn. The discharge rate in incorrect trials was comparable with that in correct trials. The neurons were considered to fire for as long as the memory of S was necessary. 5. Firing persisted even when an achromatic version or half (even a portion) of S was presented, indicating that the color, a particular portion, or the entire shape of S was not always necessary to elicit firing. 6. An S that elicited firing during the delay period invariably elicited a visual response. Neurons that fired during the delay period showed a higher stimulus selectivity than other visually responsive neurons in the anterior VMT cortex. Thus neurons that fire during the delay period represent a subgroup of visually responsive neurons that are selectively tuned to a certain stimulus. 7. More neurons fired during the delay period in the anterior VMT cortex than in the anterior IT cortex. 8. We conclude that firing during the delay period by neurons in the temporal pole reflects the short-term storage of visual information regarding a particular S.


Spin state, structure, and reactivity of terminal oxo and dioxygen complexes of the (PNP)Rh moiety.
[Rh(III)H{(tBu(2)PCH(2)SiMe(2)NSiMe(2)CH(2)PtBu{CMe(2)CH(2)})}], ([RhH(PNP*)]), reacts with O(2) in the time taken to mix the reagents to form a 1:1 eta(2)-O(2) adduct, for which O--O bond length is discussed with reference to the reducing power of [RhH(PNP*)]; DFT calculations faithfully replicate the observed O-O distance, and are used to understand the oxidation state of this coordinated O(2). The reactivity of [Rh(O(2))(PNP)] towards H(2), CO, N(2), and O(2) is tested and compared to the associated DFT reaction energies. Three different reagents effect single oxygen atom transfer to [RhH(PNP*)]. The resulting [RhO(PNP)], characterized at and above -60 degrees C and by DFT calculations, is a ground-state triplet, is nonplanar, and reacts, above about +15 degrees C, with its own tBu C--H bond, to cleanly form a diamagnetic complex, [Rh(OH){N(SiMe(2)CH(2)PtBu(2))(SiMe(2)CH(2)PtBu{CMe(2)CH(2)})}].


Alloreactive cytotoxic T lymphocyte responses to H-2 products on purified accessory cells.
Several purified accessory cell populations were examined for their capacity to stimulate allospecific cytotoxic T lymphocytes (CTL). A number of non-lymphoid accessory cells stimulated CTL directed against the whole H-2 region and to isolated Class I or Class II products of the major histocompatibility complex (MHC). The accessory cells which stimulated CTL expressed surface Ia. The generation of CTL to Class I MHC products could be inhibited by antisera directed at Class II molecules on the same accessory stimulator cell surface. These findings demonstrate the importance of Class II MHC products on heterogeneous accessory cells capable of stimulating alloreactive CTL.


An Integrated Enhanced Infant and Young Child Feeding (IYCF) and Micronutrient Powder Intervention Improved Select IYCF Practices Among Caregivers of Children Aged 12-23 Months in Eastern Uganda.
There is little evidence of the impact of integrated programs distributing nutrition supplements with behavior change on infant and young child feeding (IYCF) practices. We evaluated the impact of an integrated IYCF/micronutrient powder intervention on IYCF practices among caregivers of children aged 12-23 mo in eastern Uganda. We used pre-post data from 2 population-based, cross-sectional surveys representative of children aged 12-23 mo in Amuria (intervention) and Soroti (nonintervention) districts (n = 2816). Caregivers were interviewed in June/July at baseline in 2015 and 12 mo after implementation in 2016. We used generalized linear mixed models with cluster as a random effect to calculate the average intervention effect on receiving IYCF counseling, ever breastfed, current breastfeeding, bottle feeding, introducing complementary feeding at age 6 mo, continued breastfeeding at ages 1 and 2 y, minimum meal frequency (MMF), minimum dietary diversity, minimum acceptable diet (MAD), and consumption of food groups the day preceding the survey. Controlling for child age and sex, household wealth and food security, and caregiver schooling, the intervention was positively associated with having received IYCF counseling by village health team [adjusted prevalence difference-in-difference (APDiD): +51.6%; 95% CI: 44.0%, 59.2%]; timely introduction of complementary feeding (APDiD: +21.7%; 95% CI: 13.4%, 30.1%); having consumed organs or meats (APDiD: +9.0%; 95% CI: 1.4%, 16.6%) or vitamin A-rich fruits or vegetables (APDiD: +17.5%; 95% CI: 4.5%, 30.5%); and MMF (APDiD: +18.6%; 95% CI: 11.2%, 25.9%). The intervention was negatively associated with having consumed grains, roots, or tubers (APDiD: -4.4%; 95% CI: -7.0%, -1.7%) and legumes, nuts, or seeds (APDiD: -15.6%; 95% CI: -26.2%, -5.0%). Prevalences of some IYCF practices were low in Amuria at endline including MAD (19.1%; 95% CI :16.3%, 21.9%). The intervention had a positive impact on several IYCF practices; however, endline prevalence of some indicators suggests a continued need to improve complementary feeding practices.


Protein interaction networks of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster: large-scale organization and robustness.
High-throughput screens have begun to reveal protein interaction networks in several organisms. To understand the general properties of these protein interaction networks, a systematic analysis of topological structure and robustness was performed on the protein interaction networks of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. It shows that the three protein interaction networks have a scale-free and high-degree clustering nature as the consequence of their hierarchical organization. It also shows that they have the small-world property with similar diameter at 4-5. Evaluation of the consequences of random removal of both proteins and interactions from the protein interaction networks suggests their high degree of robustness. Simulation of a protein's removal shows that the protein interaction network's error tolerance is accompanied by attack vulnerability. These fundamental analyses of the networks might serve as a starting point for further exploring complex biological networks and the coming research of "systems biology".


Tic suppression: the medical model.
Tics are intermittent, repetitive, patterned but usually nonrhythmic motor movements or sounds performed in response to urges or involuntarily. They are the cardinal symptom required for a DSM-IV-TR diagnosis of Tourette's disorder (TD). Many children with TD present with mild tics that cause no significant impairment. However, when tics cause pain or interference, medical treatment is reasonable. This article reviews current evidence for treatment of tics in TD with medications as well as deep brain stimulation and transcranial magnetic stimulation. It concludes with some context for understanding this literature, relevant to treatment decisions and future treatment research in TD.


Identification of necroptosis-related subtypes and prognosis model in triple negative breast cancer.
Necroptosis is considered to be a new form of programmed necrotic cell death, which is associated with metastasis, progression and prognosis of various types of tumors. However, the potential role of necroptosis-related genes (NRGs) in the triple negative breast cancer (TNBC) is unclear. We extracted the gene expression and relevant clinicopathological data of TNBC from The Cancer Genome Atlas (TCGA) databases and the Gene Expression Omnibus (GEO) databases. We analyzed the expression, somatic mutation, and copy number variation (CNV) of 67 NRGs in TNBC, and then observed their interaction, biological functions, and prognosis value. By performing Lasso and COX regression analysis, a NRGs-related risk model for predicting overall survival (OS) was constructed and its predictive capabilities were verified. Finally, the relationship between risk_score and immune cell infiltration, tumor microenvironment (TME), immune checkpoint, and tumor mutation burden (TMB), cancer stem cell (CSC) index, and drug sensitivity were analyzed. A total 67 NRGs were identified in our analysis. A small number of genes (23.81%) detected somatic mutation, most genes appeared to have a high frequency of CNV, and there was a close interaction between them. These genes were remarkably enriched in immune-related process. A seven-gene risk_score was generated, containing TPSG1, KRT6A, GPR19, EIF4EBP1, TLE1, SLC4A7, ESPN. The low-risk group has a better OS, higher immune score, TMB and CSC index, and lower IC50 value of common therapeutic agents in TNBC. To improve clinical practicability, we added age, stage_T and stage_N to the risk_score and construct a more comprehensive nomogram for predicting OS. It was verified that nomogram had good predictive capability, the AUC values for 1-, 3-, and 5-year OS were 0.847, 0.908, and 0.942. Our research identified the significant impact of NRGs on immunity and prognosis in TNBC. These findings were expected to provide a new strategy for personalize the treatment of TNBC and improve its clinical benefit.


EPIC tile flow and nitrate loss predictions for three Minnesota cropping systems.
Subsurface tile drains are a key source of nitrate N (NO3-N) losses to streams in parts of the north central USA. In this study, the Erosion Productivity Impact Calculator (EPIC) model was evaluated by comparing measured vs. predicted tile flow, tile NO3-N loss, soil profile residual NO3-N, crop N uptake, and yield, using 4 yr of data collected at a site near Lamberton, MN, for three crop rotations: continuous corn (Zea mays L.) or CC, corn-soybean [Glycine max (L.) Merr.] or CS, and continuous alfalfa (Medicago sativa L.) or CA. Initially, EPIC was run using standard Soil Conservation Service (SCS) runoff curve numbers (CN2) for CC and CS; monthly variations were accurately tracked for tile flow (r2 = 0.86 and 0.90) and NO3-N loss (r2 = 0.69 and 0.52). However, average annual CC and CS tile flows were underpredicted by -32 and -34%, and corresponding annual NO3-N losses were underpredicted by -11 and -52%. Predicted average annual tile flows and NO3-N losses generally improved following calibration of the CN2; tile flow underpredictions were -9 and - 12%, whereas NO3-N losses were 0.6 and -54%. Adjusting a N parameter further improved predicted CS NO3-N losses. Predicted monthly tile flows and NO3-N losses for the CA simulation compared poorly with observed values (r2 values of 0.27 and 0.19); the annual drainage volumes and N losses were of similar magnitude to those measured. Overall, EPIC replicated the relative impacts of the three cropping systems on N fate.


Retinoic acid-mediated decrease of G (alpha S) protein expression: involvement of G (alpha S) in the differentiation of HL-60 myeloid cells.
The amount of the heterotrimeric G protein subunit G (alpha S) decreases after the induction of human myeloblastic leukemia HL-60 cells to become granulocyte-like cells in the presence of retinoic acid (RA). Compared to untreated control cells, HL-60 cells expressed decreased levels of G (alpha S) protein and mRNA levels after addition of RA to the cultures as shown by immunoblot and Northern blot analysis. The reduction of the G (alpha S) protein in HL-60 cells by antisense RNA expression was associated with (i) decreased cell doubling time; (ii) induction of a granulocyte-like phenotype; (iii) and expression of a surface marker characteristic of myeloid differentiation. Expression of a constitutively active mutant G (alpha S) (Q227L) in HL-60 cells blocked RA-induced differentiation. In contrast, treatment with forskolin, prostaglandin E2, or 8-bromo-cyclic AMP, which increase intracellular cyclic AMP (cAMP) levels, did not inhibit the RA-mediated differentiation process. No changes in cAMP levels occurred in response to RA. The present study provides insights into the involvement of G (alpha S) protein in growth regulation during differentiation of the human myeloid cell line HL-60. These data suggest that in HL-60 human myeloid cells RA-mediated decrease of G (alpha S) plays a critical role in the regulation of differentiation which is independent of intracellular cAMP.


ATP-dependent nucleosome remodeling.
It has been a long-standing challenge to decipher the principles that enable cells to both organize their genomes into compact chromatin and ensure that the genetic information remains accessible to regulatory factors and enzymes within the confines of the nucleus. The discovery of nucleosome remodeling activities that utilize the energy of ATP to render nucleosomal DNA accessible has been a great leap forward. In vitro, these enzymes weaken the tight wrapping of DNA around the histone octamers, thereby facilitating the sliding of histone octamers to neighboring DNA segments, their displacement to unlinked DNA, and the accumulation of patches of accessible DNA on the surface of nucleosomes. It is presumed that the collective action of these enzymes endows chromatin with dynamic properties that govern all nuclear functions dealing with chromatin as a substrate. The diverse set of ATPases that qualify as the molecular motors of the nucleosome remodeling process have a common history and are part of a superfamily. The physiological context of their remodeling action builds on the association with a wide range of other proteins to form distinct complexes for nucleosome remodeling. This review summarizes the recent progress in our understanding of the mechanisms underlying the nucleosome remodeling reaction, the targeting of remodeling machines to selected sites in chromatin, and their integration into complex regulatory schemes.


Past, present and future drugs for the treatment of obsessive-compulsive disorder.
In the last decades, the treatment of obsessive-compulsive disorder (OCD) has been revolutioned by the introduction into the clinical practice of the selective serotonin (5-HT) reuptake inhibitors (SSRIs), following the observation of the unique response of OCD patients to clomipramine. However, if with no doubt the 5-HT system is central to the pharmacological treatment of OCD, it is unlikely that it represents the whole story. In fact, different studies suggest abnormalities of other neurotransmitters, neuropeptides or second messengers, so that it can be hypothesized that the possible heterogeneity of pathophysiological mechanisms might underlie the different clinical pictures and responses to treatment. Moreover, latest developments in the pharmacology of SSRIs have shown that they share the common property of 5-HT reuptake blockade, but, with the exception of citalopram and escitalopram, they do interact with other receptors and systems. In this paper, the latest findings on pharmacological treatments of OCD will be reviewed, together with a focus on putative targets for future drugs, such as the glutamate system or second messengers, and the problems related to treating OCD in different ages.


SGLT2: a potential target for the pharmacogenetics of Type 2 diabetes?
The kidney has attracted the attention of diabetologists as an organ involved in the regulation of glucose homeostasis not only by gluconeogenesis, but also by renal glucose excretion. Sodium-glucose cotransporters (SGLTs), particularly SGLT2, are responsible for reabsorption of up to 99% of the filtered glucose. SGLT2 is coded by the SLC5A2 gene, which maps on chromosome 16. Pharmacological reduction of tubular glucose reabsorption results in improved glycemic control in Type 2 diabetic patients. Since the SGLTs reabsorb most of the filtered glucose (90%), it is not surprising that mutations in SLC5A2 cause familial renal glucosuria. A recent study pointed out a possible role of common genetic variation in SLC5A2 in the control of glucose homeostasis. SLC5A2 polymorphisms might therefore represent potential candidates for pharmacogenomic studies targeting the impact of these variants on the efficacy of antidiabetic treatment that is based on inhibition of SGLT2 activity.


Evaluation of complications in patients with open fractures of the upper and lower extremity treated with internal fixation after the external fixation.
Open fractures constitute an important mortality and morbidity cause among all musculoskeletal system injuries and bring along many social and economic problems. The cost occurring due to both long treatment duration and the delay in returning to work made these conditions more complicated. The present study aims to evaluate of the complications which may occur in cases with an application of internal fixation following external fixator in upper and lower extremity open fractures retrospectively. Forty-nine patients, who applied to the emergency service between 2007 and 2013, participated in this study. Thirty-two of these patients consisted of the patients to whom external fixator was first placed, and then internal fixation was performed by us, while 17 patients were treated in another center with the external fixator, and then their treatments were performed by us. All patients' injury mechanism, duration of follow-up with an external fixator, whether debridement was performed after external fixator, the period between external fixation and internal fixation, pin site infection, duration of the union, delayed union, nonunion, whether bone graft was used during internal fixation, internal fixation type, reoperation, development of osteomyelitis and follow-up parameters were recorded. Results were evaluated separately for radius, humerus, tibia and femur fractures. Of the 49 patients, 39 were male, and 10 were female. Mean follow-up time for tibia 28.6 months, for femur 34, for humerus 26.9, for Radius 27 months. Of the 49 patients who participated in this study, 15 applied with upper extremity (11 humeri, 4 Radius) injury and 34 applied with lower extremity (25 tibias, 9 femora) injury. Of the 49 patients, 32 had pin tract infection, 11 had nonunion, 11 had delayed union, two had osteomyelitis. Open fractures are always hard to treat. After external fixation to the internal fixation process have some complications, phsycians should be aware of all these problems and plan according to the situation.


A multidisciplinary motorcycle safety initiative.
Motorcycle registrations are on the rise in the United States, especially among riders over 40 years of age. While motorcycle popularity has been increasing, so have injuries and fatalities. Unfortunately, motorcycle crashes have been increasing at a disproportionately high rate. In 2007, motorcycle fatalities reached the highest level since the Department of Transportation began collecting data in 1975. Because of the increasing number of motorcycle crashes in Ohio and Central Ohio, a multidisciplinary team consisting of the Grant Medical Center's trauma program, Franklin County Safe Communities (a Columbus Public Health program), the American Motorcyclist Association, and Columbusbiker.com applied for and received a $5,000 motorcycle safety mini-grant from the American Public Health Association, Public Health Traffic Safety Institute. The mini-grant provided funding from October 2008 to September 2009. The 3 goals of the mini-grant were to promote "sharing the road" with motorcycles, inform the reentry riding community on the necessity of proper rider training, and train the Ohio injury prevention workforce on motorcycle safety and the motorcycling culture. However, the ultimate goal is to prevent death and reduce injury due to motorcycle crashes.


Carpal intra-articular blastomycosis in a Labrador retriever.
A 6-month-old male castrated Labrador retriever was presented for coughing and forelimb lameness. Blastomyces dermatitidis was identified in cytology of sputum and synovial fluid. Repeat arthrocentesis 7 months later revealed resolution of septic arthritis. Fungal septic arthritis should be considered for cases of monoarthritis and may respond to oral itraconazole treatment.


The expression of class I patatin gene fusions in transgenic potato varies with both gene and cultivar.
Patatin is a family of glycoproteins that contributes about 40% of the total soluble protein in tubers of potato (Solanum tuberosum L.). The protein is encoded by a multigene family of 50-70 genes which have been divided into classes I and II on the basis of sequence homology. The promoters of two class I genes, PS20 and PS3/27, were transcriptionally fused to beta-glucuronidase and transformed into the potato cultivars Désirée and Maris Bard. Examination of the expression levels in large populations of microtubers indicated that the PS20 promoter produced beta-glucuronidase activities 5-fold lower in Désirée than Maris Bard whereas the PS3/27 promoter showed similar levels in both cultivars. Furthermore, the relative expression levels from the two promoters were reversed in the two cultivars. The beta-glucuronidase enzyme activity was correlated with the mRNA level but not the copy number of the introduced gene. The implications for the use of patatin promoters in the genetic modification of tubers is discussed.


Surgical management of locally advanced thyroid cancer.
To summarize recent literature with respect to locally invasive thyroid cancer and discuss the variety of surgical management techniques according to the sites involved. Different philosophies for surgical strategy in patients with locally invasive thyroid cancer still exist. Intraoperative neuromonitoring assessment of the functional status of the recurrent laryngeal nerve is helpful to decide surgical extent. A staging system based on the degree of invasion has been suggested for the proper management of laryngotracheal invasion. The goal of treatment of locally invasive thyroid cancer is to maximize local control and overall survival while minimizing the morbidity of a radical resection or preserving function of adjacent vital structures with conservative procedures. It is imperative that the operating surgeon be familiar with an algorithm for the appropriate workup and surgical planning. In addition, various factors such as the patient's age, tumor biology and histopathology, previous response to treatment, presence of distant metastasis, or adjuvant therapy can affect the extent of surgical resection.


Long-term effects of a combination of isoflavones, agnus castus and magnolia extracts on climacteric symptoms and cardiometabolic risk profile in postmenopausal women.
To evaluate the long-term effects of a combination of isoflavones, agnus castus and magnolia extracts (combined isoflavone compound [CIC]) on climacteric symptoms and cardiometabolic risk in symptomatic postmenopausal women. This interventional, prospective study evaluated climacteric symptoms, mood and sleep disorders using the 21-item Greene Climacteric Scale (GCS) and 7-item Insomnia Severity Index (ISI) questionnaires; and cardiovascular, metabolic and thrombotic risk markers at baseline (T0) and after 12 months of CIC treatment (T1). In healthy postmenopausal women (N = 71), 12-month CIC treatment significantly reduced patient-reported vasomotor symptoms (100% vs. 17%), mood disorders (67% vs. 25%) and sleep disorders (89% vs. 19%%) (all p < .001) compared with baseline; and significantly improved GCS psychological, somatic, and vasomotor domain scores and ISI sleep disturbance scores (all p < .05). CIC significantly reduced systolic (p = .022) and diastolic blood pressure (p < .001), and heart rate (p < .001); glucose concentrations (p = .018), HOMA index (p = .013), and ALT (p = .035), homocysteine (p = .005) and NT-proBNP (p = .003) levels. Long-term CIC therapy improved vasomotor symptoms, mood disorders, sleep disorders, hemodynamic measurements and cardiometabolic risk markers in healthy postmenopausal women. NCT03699150.


COVID-19 or non-COVID viral pneumonia: How to differentiate based on the radiologic findings?
Influenza viruses were responsible for most adult viral pneumonia. Presently, coronavirus disease 2019 (COVID-19) has evolved into serious global pandemic. COVID-19 outbreak is expected to persist in months to come that will be synchronous with the influenza season. The management, prognosis, and protection for these two viral pneumonias differ considerably and differentiating between them has a high impact on the patient outcome. Reverse transcriptase polymerase chain reaction is highly specific but has suboptimal sensitivity. Chest computed tomography (CT) has a high sensitivity for detection of pulmonary disease manifestations and can play a key-role in diagnosing COVID-19. We reviewed 47 studies and delineated CT findings of COVID-19 and influenza pneumonia. The differences observed in the chest CT scan can be helpful in differentiation. For instance, ground glass opacities (GGOs), as the most frequent imaging finding in both diseases, can differ in the pattern of distribution. Peripheral and posterior distribution, multilobular distribution, pure or clear margin GGOs were more commonly reported in COVID-19, whereas central or peri-bronchovascular GGOs and pure consolidations were more seen in influenza A (H1N1). In review of other imaging findings, further differences were noticed. Subpleural curvilinear lines, sugar melted sign, intra-lesional vascular enlargement, reverse halo sign, and fibrotic bands were more reported in COVID-19 than H1N1, while air space nodule, tree-in-bud, bronchiectasia, pleural effusion, and cavitation were more seen in H1N1. This delineation, when combined with clinical manifestations and laboratory results may help to differentiate these two viral infections.


Leigh syndrome caused by a novel m.4296G>A mutation in mitochondrial tRNA isoleucine.
Leigh syndrome is a severe neurodegenerative disease with heterogeneous genetic etiology. We report a novel m.4296G>A variant in the mitochondrial tRNA isoleucine gene in a child with Leigh syndrome, mitochondrial proliferation, lactic acidosis, and abnormal respiratory chain enzymology. The variant is present at >75% heteroplasmy in blood and cultured fibroblasts from the proband, <5% in asymptomatic maternal relatives, and is absent in 3000 controls. It is located in the highly conserved anticodon region of tRNA(Ile) where three other pathogenic changes have been described. We conclude that there is strong evidence to classify m.4296G>A as a pathogenic mutation causing Leigh syndrome.


Bacteriophages induced from lysogenic root canal isolates of Enterococcus faecalis.
Bacterial viruses play crucial roles in the pathogenesis of many systemic diseases. They are known to inhabit the oral cavity, both as free virions and as prophages in lysogenic bacterial strains; however, there has been no report of bacteriophages in endodontic infections. In this study, we sought to detect, isolate, and describe temperate bacteriophages harbored by Enterococcus faecalis strains isolated from endodontic infections. Ten E. faecalis strains were isolated from root canals of teeth undergoing retreatment following unsuccessful endodontic therapy. Mitomycin C was used to induce any prophages present in the bacterial isolates. The induced phages were purified and examined using electron microscopy. The DNA extracted from one of the phage isolates was subjected to restriction endonuclease digestion and agarose electrophoresis analysis. Lysogeny was demonstrated in 4 of the 10 E. faecalis strains. Three of the lysogenic strains yielded phages exhibiting a Siphoviridae morphology, with long, non-contractile tails 130 nm in length, and spherical/icosahedral heads 41 nm in diameter. The virus induced from the fourth lysogenic E. faecalis strain had a contractile tail characteristic of Myoviridae. Restriction endonuclease analysis of NsiI and NdeI DNA fragments from one of the Siphoviridae phage isolates (phage phiEf11) indicated a genome size of approximately 41 kbp. This is the first report of lysogenic bacteria and their inducible viruses in infected root canals.


Pepper Commission recommends universal health care coverage.
Many Americans are without adequate health care as costs continue to rise. Health care insurance is unaffordable or unavailable to over half the working poor, but hospitals can no longer bear the expense of uncompensated care. The United States Bipartisan Commission on Comprehensive Health Care has issued recommendations to Congress entitled "Health Care and Long Term Care for All Americans." The Commission plan proposes a system that would be phased in over several years. This article discusses phases of the system from the first through the fifth year.


Should prospective dental students be screened for colour vision deficits?
A perennial question in dental education is: what skills and aptitudes should be assessed in prospective dental students? Intellectual capacity and manual dexterity understandably rank highly, but are there minimum thresholds for visual perception that applicants need be able to demonstrate before they enter the profession? We have recently flagged this issue with regard to the thresholds of stereoscopic acuity required for a dentist when operating on teeth. In the present article, we highlight the issue of identifying a minimum acceptable level of colour vision.


Epitope mapping of the Ro/SSA60KD autoantigen reveals disease-specific antibody-binding profiles.
Anti-Ro60KD autoantibodies are commonly found in sera from patients with primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). In order to identify the epitopes of this autoantigen, 22-mer, synthetic peptides overlapping by eight residues, and covering the entire sequence of the Ro60KD autoantigen were prepared. Three groups of sera were evaluated according to their autoantibody specificites. The first group consisted of monospecific anti Ro60KD sera from four patients with SLE and one with SS, the second one was composed of anti-Ro60KD+anti-La(SSB)-positive sera from four patients with SS and the third group included three normal sera and one anti Ro52KD serum. It was found that sera from SLE patients interact with a common antigenic site spanning the sequence TKYKQRNGWSHKDLLRSHLKP (169-190) of the Ro60KD protein. On the other hand, sera from SS patients recognise the ELYKEKALSVETEKLLKYLEAV (211-232) region of this autoantigen. Determination of the minimal required peptide length for optimal antibody recognition showed that the defined epitopes can be shortened to the NGWSHKDLLR (175-184) and KALSVETEKLLKYLEAV (216-232) sequences respectively. Inhibition experiments using the Ro60KD antigen and soluble peptides corresponding to the 175-184 and 216-232 segments further confirmed the specific antibody binding. These results, although only a small number of sera were used, indicate that the Ro60KD autoantigen, which is not characterized by disease specificity, contains two discrete epitopes specifically recognized from SLE and SS patient sera. Finally, the sequence similarity of the NGWSHKDLLR (175-184) epitope with some of the HLA haplotypes, associated with anti-Ro response, deserves to be noted.


Impaired response of polycythemic mice to erythropoietin induced by protein starvation imposed after hormone administration.
The present study was performed to determine the stage of the erythropoietic pathway which is affected by starvation or protein deprivation and whose manifestation is a depressed response to exogenous erythropoietin (EPO). The response to recombinant human EPO was measured in post-hypoxic polycythemic mice by determination of 59Fe uptake into red cells, spleen and femur and/or erythroid colony forming units (CFU-E) and erythroid precursor cell concentrations in femoral marrow. Experimental mice were either starved or fed one of seven different diets whose protein (casein) content ranged from 0 to 20%. All diets were isocaloric. The response of mice maintained on the standard diet (Purina Lab chow) was taken as the normal one. Starvation during the 48-hour period immediately before EPO injection had no effect on the response to the hormone. Starvation, and protein deprivation to a lesser extent, during the 48-hour period following EPO, on the other hand, significantly reduced the response. There was a progressive increase in the response as the casein content of the diet was increased. A normal response was observed when dietary casein concentration was 10%. These findings indicate that nutritional deprivation or dietary protein alterations during the period immediately following EPO injection in polycythemic mice can have detrimental effects on the erythroid response in a model in which nutritional deprivation was relatively short and acute. They also indicate that the subnormal response is not due to a decreased size of the erythroid progenitor pool available for differentiation but to deficient rates of differentiation of erythropoietic units.


[Effect of heparin on platelet aggregation in vitro].
Heparin added to citrated platelet rich plasma influences shape change and aggregation of platelets in different ways. In the presence of heparin neither ADP nor collagen induces shape change, while shape change after thrombin or arachidonic acid remains unaltered. Heparin potentiates the first aggregation step induced by ADP and epinephrine but inhibits aggregation induced by thrombin and ristocetin. The second phase of aggregation and the release reaction are not directly influenced by heparin no matter which aggregation agent is used.