rmtA-Dependent Transcriptome and Its Role in Secondary Metabolism, Environmental Stress, and Virulence in Aspergillus flavus.
Aspergillus flavus colonizes numerous oil seed crops such as maize, peanuts, treenuts and cottonseed worldwide, contaminating them with aflatoxins and other harmful toxins. Previously our lab characterized the gene rmtA, which encodes an arginine methyltransferase in A. flavus, and demonstrated its role governing the expression of regulators in the aflatoxin gene cluster and subsequent synthesis of toxin. Furthermore, our studies revealed that rmtA also controls conidial and sclerotial development implicating it as an epigenetic regulator in A. flavus To confirm this, we performed a RNA sequencing analysis to ascertain the extent of rmtA's influence on the transcriptome of A. flavus In this analysis we identified over 2000 genes that were rmtA-dependent, including over 200 transcription factor genes, as well as an uncharacterized secondary metabolite gene cluster possibly responsible for the synthesis of an epidithiodiketopiperazine-like compound. Our results also revealed rmtA-dependent genes involved in multiple types of abiotic stress response in A. flavus Importantly, hundreds of genes active during maize infection were also regulated by rmtA In addition, in the animal infection model, rmtA was dispensable for virulence, however forced overexpression of rmtA increased mortality with respect to the wild type.


Characterization of a set of T7 RNA polymerase active site mutants.
We have evaluated the elongation rates, processivities, and abortive transcription characteristics of a set of T7 RNA polymerase mutants that map to the polymerase active site. The effects of these mutations on transcription are complex: they cause decreases in activity and processivity during both the processive and abortive phases of transcription and exhibit disproportionate decreases in activity and processivity on poly(dA).poly(dT) or poly(dT) versus poly(dG).poly(dC) templates. They also exhibit an increase in the proportion of slippage dependent poly(G) transcript synthesis during the initial stages of transcription. It is shown that these multiple, distinct effects on transcription can be attributed to decreases in the mutant enzymes' phosphodiester bond formation rates. Estimates of the decreases in these rates are derived from the measured transcript elongation rates and processivities of the mutant enzymes.


Extreme mtDNA homogeneity in continental Asian populations.
Mitochondrial DNA (mtDNA) variation in continental Asia has not been well-studied. Here, we report mtDNA HV1 sequences for 84 Xi'an and 82 Changsha Han Chinese, 89 Honshu Japanese, and 35 Vietnamese. Comparison of these sequences with other Asian mtDNA sequences reveals high variability within populations, but extremely low differentiation among Asian populations. Correlations between genetic distance and geographic distance, based on mtDNA and Y chromosome variation, indicate a higher migration rate in females than in males. This may reflect patrilocality, as suggested previously, but another plausible hypothesis is that the demographic expansion associated with the spread of agriculture in Asia may be responsible for the extreme genetic homogeneity in Asia.


Hepatobiliary abnormalities on sonography in children with HIV infection.
Our purpose was to characterize the spectrum of hepatobiliary abnormalities on sonography in children with vertically transmitted HIV infection. Abdominal sonograms were performed on 41 children with HIV infection and correlated with clinical and histopathologic data. Hepatobiliary abnormalities were noted in 26 (63%) children. Hepatomegaly (n = 13) and abnormal hepatic echotexture (n = 13) were the most common abnormalities noted. Preexisting AIDS-related infections or neoplasms were noted significantly more frequently in children with hepatic or biliary abnormalities on sonography (18/26, 69%) than in children without abnormalities (5/15, 33%) (P = 0.0001). Most children with hepatobiliary abnormalities on sonography who underwent hepatic tissue sampling, however, did not have evidence of acute infection or neoplasia. Hepatobiliary abnormalities are frequently noted on sonography in children with HIV infection. Hepatomegaly and abnormal hepatic echotexture are the most frequent sonographic findings and are usually nonspecific.


Comparison of different models for estimation of direct and maternal genetic parameters on body weights in Awassi sheep.
The present study was conducted to estimate the (co)variance components for birth and weaning weight (BW and WW) in 8142 Awassi sheep between 2015 and 2017. Estimates were calculated with single-trait analysis by the average information restricted maximum likelihood (AI-REML) method, using a derivative-free algorithm by fitting six different univariate animal models. The negative of the log-likelihood function (LogL), Akaike information criterion (AIC), and Bayesian information criterion (BIC) tests were used for selecting the best fitted model. In addition, the goodness of fit between the two models was compared with the likelihood ratio test (LRT). Depending on the models, h a 2 and h m 2 ranged from 0.230 to 0.240 and 0.015 to 0.033 for BW, and 0.108 to 0.168 and 0.024 to 0.081 for WW, respectively. Model 3 for BW and Model 2 for WW were chosen as the best models by LogL comparison criteria. According to the LRT ratio test Model 2, Model 3, and Model 4 for BW and Model 2, Model 3, Model 4, Model 5, and Model 6 for WW were significant ( p < 0.05 ). Including maternal genetic or maternal permanent environmental effects in these models was found to be significant in terms of parameter estimates.


[Vegetation and its relation with climate conditions near the timberline of Beitai, the Xiaowutai Mts., northern China].
On the basis of field investigations, the timberline range of Beitai, the Xiaowutai Mountains was carved up, and the changes in the makeup and diversity of plants with the altitude were discussed. The results showed that the timberline with gradual changes in the northern slope of Beitai ranged from 2620-2800 m. In timberline, herbaceous plants were rich, and the diversity was higher than that in coniferous forest and sub-alpine meadow zones. The turnover rates of species were gradually hoisting from the centre of timberline to sub-alpine meadow and forest zones, and highest at the edge of timberline. Betula, Picea meyreri and Larix principis-ruprechtii species were the ecological indicator for research on environmental changes. Climate indication significance of these arbor species distributed in and near the timberline was also discussed.


Coral larval settlement induction using tissue-associated and exuded coralline algae metabolites and the identification of putative chemical cues.
Reef-building crustose coralline algae (CCA) are known to facilitate the settlement and metamorphosis of scleractinian coral larvae. In recent decades, CCA coverage has fallen globally and degrading environmental conditions continue to reduce coral survivorship, spurring new restoration interventions to rebuild coral reef health. In this study, naturally produced chemical compounds (metabolites) were collected from two pantropical CCA genera to isolate and classify those that induce coral settlement. In experiments using four ecologically important Caribbean coral species, we demonstrate the applicability of extracted, CCA-derived metabolites to improve larval settlement success in coral breeding and restoration efforts. Tissue-associated CCA metabolites induced settlement of one coral species, Orbicella faveolata, while metabolites exuded by CCA (exometabolites) induced settlement of three species: Acropora palmata, Colpophyllia natans and Orbicella faveolata. In a follow-up experiment, CCA exometabolites fractionated and preserved using two different extraction resins induced the same level of larval settlement as the unfractionated positive control exometabolites. The fractionated CCA exometabolite pools were characterized using liquid chromatography tandem mass spectrometry, yielding 145 distinct molecular subnetworks that were statistically defined as CCA-derived and could be classified into 10 broad chemical classes. Identifying these compounds can reveal their natural prevalence in coral reef habitats and facilitate the development of new applications to enhance larval settlement and the survival of coral juveniles.


Differential diagnosis of emotional disorders that cause weight loss.
Recently, anorexia nervosa has received much attention in the scientific and lay press. As a result there is a danger that the other emotional disorders that can present with weight loss and vomiting will be overlooked. Case examples are presented for anorexia nervosa, conversion disorder, schizophrenia and depression. The presentation and treatment of these four disorders are compared.


Investigation of effective climatology parameters on COVID-19 outbreak in Iran.
SARS CoV-2 (COVID-19) Coronavirus cases are confirmed throughout the world and millions of people are being put into quarantine. A better understanding of the effective parameters in infection spreading can bring about a logical measurement toward COVID-19. The effect of climatic factors on spreading of COVID-19 can play an important role in the new Coronavirus outbreak. In this study, the main parameters, including the number of infected people with COVID-19, population density, intra-provincial movement, and infection days to end of the study period, average temperature, average precipitation, humidity, wind speed, and average solar radiation investigated to understand how can these parameters effects on COVID-19 spreading in Iran? The Partial correlation coefficient (PCC) and Sobol'-Jansen methods are used for analyzing the effect and correlation of variables with the COVID-19 spreading rate. The result of sensitivity analysis shows that the population density, intra-provincial movement have a direct relationship with the infection outbreak. Conversely, areas with low values of wind speed, humidity, and solar radiation exposure to a high rate of infection that support the virus's survival. The provinces such as Tehran, Mazandaran, Alborz, Gilan, and Qom are more susceptible to infection because of high population density, intra-provincial movements and high humidity rate in comparison with Southern provinces.


Influence of Solvent Swelling on Ultrafast Structural Dynamics in Polydimethylsiloxane Thin Films by Two-Dimensional IR Spectroscopy.
Fourier transform infrared and two-dimensional IR (2D-IR) spectroscopies were applied to polydimethylsiloxane (PDMS) cross-linked elastomer and a siloxane oligomer without solvent and swollen or dissolved in various solvents. The silicon hydride, which is covalently bound to the polymer chains, was the vibrational probe for the systems studied. There is almost an absence of vibrational solvatochromism in these systems. Frequency-frequency correlation functions obtained by 2D-IR spectroscopy show that the insensitivity of the FTIR spectra is due to overwhelming heterogeneity. However, the homogeneous contribution to the FTIR spectrum is smaller for the elastomer than the oligomer showing that the cross-linking process restricts the frequency fluctuations that are experienced by the hydride mode. The silicon hydride mode in a cross-linked, solvent-free PDMS film also exhibits spectral diffusion that must be due to polymer structural motions on the ultrafast time scale that are active above the glass transition temperature. Once solvents penetrate and swell the elastomer, the polymer likely continues to experience these polymer structural motions. However, we find that the vibrational dynamics are characteristic of the infiltrating solvents, showing that at least some fraction of the measured dynamics originate in solvent motions.


Can the Hartree-Fock kinetic energy exceed the exact kinetic energy?
The Hartree-Fock (HF) approximation has been an important tool for quantum-chemical calculations since its earliest appearance in the late 1920s and remains the starting point of most single-reference methods in use today. Intuition suggests that the HF kinetic energy should not exceed the exact kinetic energy; but no proof of this conjecture exists, despite a near century of development. Beginning from a generalized virial theorem derived from scaling considerations, we derive a general expression for the kinetic energy difference that applies to all systems. For any atom or ion, this trivially reduces to the well-known result that the total energy is the negative of the kinetic energy and, since correlation energies are never positive, proves the conjecture in this case. Similar considerations apply to molecules at their equilibrium bond lengths. We use highly precise calculations on Hooke's atom (two electrons in a parabolic well) to test the conjecture in a nontrivial case and to parameterize the difference between density functional and HF quantities, but find no violations of the conjecture.


AcGI1, a novel genomic island carrying antibiotic resistance integron In687 in multidrug resistant Achromobacter xylosoxidans in a teaching hospital in Thailand.
This study investigated the genetic basis of multidrug resistance in two strains of Achromobacter xylosoxidans isolated from patients attending a hospital in Thailand in 2012. These isolates were highly resistant to cephalosporins, aminoglycosides, fluoroquinolones, co-trimoxazole and carbapenems. Whole genome sequencing revealed that the two isolates were not clonally related and identified a carbapenem resistance gene-habouring integron (In687), residing in a novel genomic island, AcGI1. This In687 shares 100% identical nucleotide sequence with ones found in Acinetobacter baumannii Aci 16, isolated from the same hospital in 2007. We report the first analysis of multidrug-resistant A. xylosoxidans isolated in Thailand, and the first example of this island in A. xylosoxidans. Our data support the idea that resistance has spread in Thailand via horizontal gene transfer between species and suggest the possibility of A. xylosoxidans may serve as a reservoir of antibiotic resistance, especially in hospital setting.


Putative functions of PrP(C).
While the exact function of the cellular prion protein (PrP(C)) remains unknown, there are several leads due to increasing knowledge on the localisation and interaction of PrP(C) with other molecules. This chapter will concentrate on these aspects. Identified ligands of PrP(C) mainly belong to the categories of heat-shock proteins, membrane-bound receptors, or heparan sulphates. The possible synaptic role of PrP(C) has been exemplified by electrophysiological findings in PrP(o/o) mice and the studies of PrP(C) as a copper-binding molecule that could regulate the copper content of the synaptic cleft. The latter property of PrP(C) may also endow PrP(C) with the activity of a copper-dependent superoxide dismutase. Binding of PrP(C) to signalling molecules suggests a role as a transmitter of information from the extracellular milieu to the cell and a trigger for a molecular cascade. This agrees with new data on PrP(C) receptors and the role of PrP(C) in cell survival.


Crystallization kinetics of polydisperse colloidal hard spheres: experimental evidence for local fractionation.
We present the crystallization kinetics for two polydisperse hard-sphere particle stocks with differing particle size distributions. One of the latexes had a relatively symmetrical distribution, the other had a more polydisperse distribution, which was highly skewed to smaller sizes. The emerging Bragg reflections from the crystallizing samples were measured using a technique that provides improved statistical averaging over our previous methods. It was observed that, for the more polydisperse particles, the onset of nucleation was delayed by up to an order of magnitude in reduced time, and displayed qualitatively different growth behavior compared to the particles with the more symmetric size distribution. Based on these measurements and time lapse photographs, we propose a growth mechanism whereby crystallization occurs in conjunction with a local fractionation process near the crystal-fluid interface, which significantly alters the kinetics of crystallite nucleation and growth. This fractionation effect becomes more significant as polydispersity or skewness increases.


Uterine Perforation with Intra-Abdominal Clostridium perfringens Gas Gangrene: A Rare and Fatal Infection.
Background:Clostridium perfringens gas gangrene is an extremely rare and fatal infection. Necrosis of the myometrium is rarely seen and has only been recorded in 18 cases to date. Of these 18 reported cases, only 5 have occurred in nonpregnant women. This article presents the 6th case of myometrium necrosis from C. perfringens.Case: A 72-year-old woman, gravida 2, para 2, presented with abdominal pain and vaginal bleeding. After examinations, laboratory testing, and several surgical interventions, she was found to have C. perfringens infection and advanced high-grade serous adenocarcinoma of the endometrium with >50% invasion into the myometrium. Results: Despite the surgical interventions and use of several antibiotics, this patient did not improve. She was weaned from treatment per her advance directive and died after weaning. Conclusions: Awareness of the many etiologies for peritonitis is of great importance when a fatal infection may be the cause of the condition. Correct diagnosis and proper treatment is essential for the survival of patients infected with C. perfringens. (J GYNECOL SURG 32:182).


Advances in radioguided surgery in oncology.
The sentinel lymph node (SLN) biopsy is probably the most well-known radioguided technique in surgical oncology. Today SLN biopsy reduces the morbidity associated with lymphadenectomy and increases the identification rate of occult lymphatic metastases by offering the pathologist the lymph nodes with the highest probability of containing metastatic cells. These advantages may result in a change in clinical management both in melanoma and breast cancer patients. The SLN evaluation by pathology currently implies tumor burden stratification for further prognostic information. The concept of SLN biopsy includes pre-surgical lymphoscintigraphy as a "roadmap" to guide the surgeon toward the SLNs and to localize unpredictable lymphatic drainage patterns. In addition to planar images, SPECT/CT improves SLN detection, especially in sites closer to the injection site, providing anatomic landmarks which are helpful in localizing SLNs in difficult to interpret studies. The use of intraoperative imaging devices allows a better surgical approach and SLN localization. Several studies report the value of such devices for excision of additional sentinel nodes and for monitoring the whole procedure. The combination of preoperative imaging and radioguided localization constitutes the basis for a whole spectrum of basic and advanced nuclear medicine procedures, which recently have been encompassed under the term "guided intraoperative scintigraphic tumor targeting" (GOSTT). Excepting SLN biopsy, GOSTT includes procedures based on the detection of target lesions with visible uptake of tumor-seeking radiotracers on SPECT/CT or PET/CT enabling their subsequent radioguided excisional biopsy for diagnostic of therapeutic purposes. The incorporation of new PET-tracers into nuclear medicine has reinforced this field delineating new strategies for radioguided excision. In cases with insufficient lesion uptake after systemic radiotracer administration, intralesional injection of a tracer without migration may enable subsequent excision of the targeted tissue. This approach has been helpful in non-palpable breast cancer and in solitary pulmonary nodules. The introduction of allied technologies like fluorescence constitutes a recent advance aimed to refine the search for SLNs and tracer-avid lesions in the operation theatre in combination with radioguidance.


Development of a dual label fluorescence technique that can be utilized to elucidate the mechanism of action of monoclonal antibody-drug conjugates.
A method is described that allows the simultaneous visualization and relative assessment of both the antibody and drug components of monoclonal antibody-drug conjugates at the target cell membrane. The antibody is detected by a fluorescein-conjugated anti-mouse immunoglobulin serum while the drug is visualized by rhodamine avidin or phycoerythrin-streptavidin binding to a biotinylated anti-Vinca alkaloid monoclonal antibody. This technique was effective in demonstrating the cell surface localization of a monoclonal antibody-Vinca alkaloid conjugate to human lung adenocarcinoma cells grown in vitro and was also used to demonstrate targeting of the conjugate in vivo to the membranes of these same tumor cells grown as a nude mouse xenograft. This method was also utilized to help elucidate the mechanism of action of monoclonal antibody-drug conjugates.


The construct and predictive validity of different approaches to combining urine and self-reported drug use measures among older adolescents after substance abuse treatment.
Reconciling urine results and self-reports is a classic challenge in substance abuse treatment research in general. For adolescents, the problems are compounded by the facts that they are more likely to use marijuana (which takes longer to metabolize) and to be coerced into treatment (which may increase lying). This article examines the construct and predictive validity of several different approaches for combining urine and self reported drug use including using common individual measures (urine tests and self-reported recency, frequency, and peak use), taking either as positive, using a summary scale, and using a latent model. Data are from 819 older adolescents 24 to 42 months after intake in seven sites. Days of use, the GAIN's substance frequency scale, and a latent model were the three best methods in terms of construct and predictive validity. Implications for treatment and longitudinal evaluation will be discussed.


Systemic treatment of acute liver failure with adipose derived stem cells.
The definitive treatment for liver failure is, currently, liver transplantation. Research into other possible treatments, focused on achieving regeneration of the liver parenchyma, have led to the development of methods to generate hepatocytes from stem cells. In our study, we transplant allogenic adipose-derived stem cells (ASCs), not previously differentiated to hepatocytes, to treat acute liver failure induced by intraperitoneal administration of carbon tetrachloride (CCl4) in a Sprague-Dawley rat model. The ASCs were delivered via the tail vein, having previously been labeled with PKH26, a fluorescent membrane marker. Two control groups were established, Group 1(n = 15) consisting of olive oil (5 mL/kg) and Group 2(n = 15): 1 × 10(6) PKH26-labeled ASCs. Further, two study groups, Group 3(n = 30): CCl4 dissolved in olive oil and Group 4(n = 30): CCl4 dissolved in olive oil and 1 × 10(6) PKH26-labeled ASCs completed the experimental design. Blood samples were analyzed, finding AST and ALT levels significantly higher in treatment over control groups at 24 and 48 hours. The mortality rates were statistically different between control groups and Group 3 (Group 1-3 p = .04, Group 2-3 p = .04) and between Groups 3 and 4 (p = .02). Examining the liver parenchyma, a significantly higher number of ASCs were observed in Group 4 than in Group 2 at all time points (p = .00). The intravenous injection of allogenic ASCs in this model of CCl4-induced liver failure reduced the mortality in treated animals. ASCs injected in the rat tail vein were found in the liver in animals with induced acute liver failure.


Simple bone cyst of the mandible: report of two cases.
Despite their names, simple bone cysts are no longer categorized as cysts since they lack an epithelial lining. However, their nature remains controversial. The internal structure is totally radiolucent, sometimes showing multilocular appearance, although the lesion does not contain true septa and the ridges of bone is produced by the scalloping effect. We presented two cases of histopathologically confirmed simple bone cyst. Radiographic features such as multilocular appearance and significant buccal and lingual expansion are not usual findings for simple bone cyst, whereas evident in our presented cases.


Attributable mortality of hospital-acquired bloodstream infections in Ireland.
To estimate the attributable mortality of hospital-acquired bloodstream infections (HA-BSI) in Ireland. A retrospective case-cohort study was conducted, based on notifications from Irish microbiology laboratories and administrative patient records from six Irish hospitals from January 2007 to December 2013. Probabilistic linkage was used to link 1252 cases of bloodstream infection from a cohort of 343,189 hospitalized patients. Independent predictors of mortality were determined using a multi-variable logistic regression model, and included: patient age, emergency or re-admission to hospital, length of stay in an intensive care unit, number of procedures, number of diagnoses, major diagnostic category and presence of HA-BSI. Attributable mortality was calculated from the crude mortality of case subjects after adjusting for other predictors of mortality, and was found to be 15.3% (95% confidence interval 14.8-15.8%). The study was further stratified according to the causative organism, including: Escherichia coli, Enterococcus faecium, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae, and, where available, their antimicrobial resistance patterns. The highest attributable mortality among these organisms was reported for E. faecium at 18.1% and the lowest attributable mortality was reported for E. coli at 13.6%. A significantly higher attributable mortality was found for antimicrobial resistance patterns of some organisms, most notably for meticillin-resistant S. aureus at 19.5%, vs meticillin-susceptible S. aureus at 13.3%. HA-BSI is an important cause of mortality, and attributable mortality differs significantly among causative organisms and antimicrobial resistance patterns.


Women younger than 50 years with endometrial cancer.
The purpose of the study was to evaluate if known risk factors for endometrial cancer in menopausal women are also related to endometrial cancer in younger ages. Eighty-one patients with a mean age of 46.3 years diagnosed with endometrial cancer (EC) (histologically confirmed) from January of 1992 to December of 2004 were included in the study. The EC group of patients was compared with 100 patients (control group) randomly selected from the gynecologic clinic (inclusion criteria: age 43-48 years) without any endometrial cancer diagnoses that were evaluated for the same factors. Mean BMI was 34.4 kg/m2 (SD = 8.8) in the first group and 28.3 (SD = 7.6) in the second one (p < 0.001). None of the women in the EC group reported any history of oral contraception. With the exception of hypertension and ovarian cancer (probably related to small numbers) all other comparisons were statistically significant (although some only marginally). From the results of our study, it seems that body mass index (BMI), parity, type of menstrual cycles, history of polycystic ovarian (PCO) syndrome and diabetes are possibly related to endometrial cancer in women younger than 50 years of age, and the strongest relation was found with increased BMI. Also, there was no increased incidence of hypertensive disease in the EC group. Prospective studies are needed for final conclusions.


Leptin is not involved in the pathophysiology of endometriosis-related infertility.
Changes in peritoneal fluid (PF) composition may affect fertilization as well as early embryonic development. Leptin, an adipocyte hormone, has been shown to act as a link between adipose tissue and the reproductive system. Therefore, we decided to assess peritoneal and serum leptin levels in infertile endometriotic patients. Seventy-two women were studied, including 30 fertile and 18 infertile women with ovarian endometriotic cysts and, as a reference group, 24 patients with unexplained infertility. No significant difference in the peritoneal and leptin levels was found between the studied groups. Significantly higher PF leptin concentration was observed in patients with stages III and IV of endometriosis as compared to those with minimal stage of the disease. In fertile patients with endometriosis a positive correlation has been found between PF and serum leptin concentrations. No differences in peritoneal or serum leptin levels between infertile and fertile women with endometriosis suggest that this cytokine is not involved in pathophysiology of endometriosis-related infertility.


Is vasculo-neural ingrowth the cause of pain in chronic Achilles tendinosis? An investigation using ultrasonography and colour Doppler, immunohistochemistry, and diagnostic injections.
The purpose of this study was to investigate where the pain comes from in chronic mid-portion Achilles tendinosis, by using ultrasonography and colour Doppler, immunohistochemistry, and diagnostic injections. Twenty-five tendons in 24 patients (mean age 47 years) with the clinical diagnosis of painful chronic mid-portion Achilles tendinosis, and 20 tendons in 14 controls (mean age 48 years) with pain-free Achilles tendons were examined with ultrasonography and colour Doppler. For the 25 painful tendons, a local anaesthetic was injected in the area with neovascularisation outside the ventral part of the tendon. Biopsies taken from tendinosis tissue in six patients were used for PGP 9.5 immunohistochemistry. A neovascularisation, inside and outside the ventral part of the area with tendon changes, was demonstrated in all painful tendinosis tendons, but not in any of the pain-free control tendons. After injection of the local anaesthetic towards the neovessels outside the ventral part of the tendon, the pain during tendon-loading activity was temporarily cured in all patients. The mean VAS-score for heel-raises decreased significantly from 75 mm to 6 mm. In biopsies, PGP 9.5 immunohistochemistry showed nerve structures in the vicinity of blood vessels. In conclusion, we demonstrate findings which support neovessels and accompanying nerves being the possible source of pain in chronic mid-portion Achilles tendinosis.


Evidence for a structural relationship between BRCT domains and the helicase domains of the replication initiators encoded by the Polyomaviridae and Papillomaviridae families of DNA tumor viruses.
Studies of DNA tumor viruses have provided important insights into fundamental cellular processes and oncogenic transformation. They have revealed, for example, that upon expression of virally encoded proteins, cellular pathways involved in DNA repair and cell cycle control are disrupted. Herein, evidence is presented that BRCT-related regions are present in the helicase domains of the viral initiators encoded by the Polyomaviridae and Papillomaviridae viral families. Of interest, BRCT domains in cellular proteins recruit factors involved in diverse pathways, including DNA repair and the regulation of cell cycle progression. Therefore, the viral BRCT-related regions may compete with host BRCT domains for particular cellular ligands, a process that would help to explain the pleiotropic effects associated with infections with many DNA tumor viruses.


Risk factors for catheter-related bloodstream infections in patients with intestinal failure undergoing home parenteral nutrition: a single-center study.
The incidence and risk factors of catheter-related bloodstream infections (CRBSI) in patients with intestinal failure (IF) have not been established, partly because catheter management methods vary from different facilities. This study aimed to identify the risk factors and incidence rate of CRBSIs in patients with IF who were given prophylactic treatment. Sixteen patients with IF who required home parenteral nutrition were enrolled in this study. Prophylactic management of CRBSI included monthly ethanol lock therapy and standardized infection prevention education. The outcomes included the incidence and risk factors of CRBSI. The median incidence rate of CRBSI was 1.2 per 1000 catheter days. Univariate analysis showed that the risk of developing CRBSI was significantly associated with short bowel syndrome (< 30 cm) (p = 0.016). Other relevant findings included a significant negative correlation between serum albumin and CRBSI rate (r = - 0.505, p = 0.046), and past history of mixed bacterial infections was significantly associated with increased CRBSI rate (p = 0.013). CRBSIs can still develop despite undergoing prophylactic management. Risk factors for CRBSI include the residual intestinal length, nutritional status, and susceptibility to certain microorganisms.


Unilateral distal molar movement with an implant-supported distal jet appliance.
With the guidance of the basis of the distal jet appliance, we present a new implant-supported distal jet appliance. In this case, we used a modified distal jet appliance that was supported by a palatal implant placed at the anterior edge of the rugae region of the palate for molar distalization. The treatment results were evaluated from lateral cephalometric and panoramic radiographs and dental casts. We conclude that an implant-supported modified distal jet appliance is effective in the correction of a Class II molar relationship.


Metastasis-associated gene 1 promotes invasion and migration potential of laryngeal squamous cell carcinoma cells.
Overexpression of the metastasis-associated gene 1 (MTA1) has previously been found to be associated with progression of various cancer types to the metastasis stage. The function of MTA1 in laryngeal squamous cell carcinoma (LSCC) remains unclear. To explore the significance of MTA1 in the invasion and migration processes in LSCC, gene transfection and RNA interference (RNAi) were performed to study the biological function of MTA1 in the LSCC cell line, HEP-2. Results showed that MTA1 promoted the invasion, adhesion and migration behavior of LSCC cells. RNAi against MTA1 significantly decreased the malignant phenotypes of cancer cells. MTA1 may be important in the process of LSCC invasion and metastasis.


Evolution characteristics of temporal and spatial pattern of Russian economic differences since the 21st century.
Under the background of "the Belt and Road" and "the economic corridor of China, Mongolia and Russia" initiatives, it is of great significance to study the temporal and spatial economic pattern in the Russian Federation. Based on the economic development difference index, regional economic grade index, global trend analysis tool and spatial autocorrelation model, this paper analyzes the temporal and spatial pattern evolution characteristics of Russian economic differences from 2002 to 2020. The results are as following. First, although the economic imbalance among various federal subjects has been decreasing, the economic polarization has been still severe between the prosperous developed regions and the stagnant backward regions during 2002-2020. Russia's economy shows a trend of changing from significant positive correlation in strong agglomeration space to positive correlation in weak agglomeration space, and then to random distribution. Second, there has been great differences of the economic development among various federal subjects. The economic grade of the Russian federal subjects presents a significant spatial differentiation pattern. The Russian Federation's economic resources are concentrated in the first-class federal subject (Moscow City), second-class federal subjects (Tumen Region, Moscow Region and Saint-Petersburg city) and a few third-class federal subjects (Yamalo-Nenetsky Autonomous Area, Khanty-Mansiysky Autonomous Area, Republic of Tatarstan, Krasnodar Territory, Sverdlovsk Region, etc). Third, the Russian Federation's economy presents "High Core, Low Periphery", "High West, Low East" and "High south, Low north" spatial differentiation pattern. The economic hot regions coincide with the high-class economic regions, which are mainly distributed in the contiguous areas of Ural Federal District and Volga Federal District, as well as the Moscow City, Moscow Region, Saint-Petersburg city, Krasnodar Territory and Rostov Region. The economic cold regions coincide with the low-class economic regions, which are mainly located in the Far East Federal District, the east of Siberian Federal District, the north of North West Federal District and the south of North-Caucasian Federal District. Finally, we suggest the recommendation for policy makers in Russia. And we propose the future research ideas.


Lactate distribution in the blood during progressive exercise.
The purpose of this study was to examine the effect of increment durations of 1-min and 4-min during progressive incremental exercise tests on: 1) the distribution of lactate between plasma and red blood cells (RBCs), and 2) lactate threshold (LT) detection via three conventional methods using whole blood lactate concentration ([La]) or plasma [La]. Eight males (age, 22.5 +/- 0.6 yr: height, 170.6 +/- 2.3 cm, weight, 76.0 +/- 3.1 kg, and VO2peak, 42.8 +/- 2.0 mL.kg-1.min-1) performed two progressive load tests to volitional fatigue on a cycle ergometer. Work rate was increased 30 W at 1-min or 4-min intervals. All data were normalized to individual LT work rates. For both protocols, whole blood [La], plasma [La], RBC [La], and [La] gradient increased significantly (P < 0.05) after exercise intensity exceeded LT. However, the RBC:plasma [La] ratio remained at the resting value throughout the progressive exercise tests. The increase in [La] gradient after LT, with no change in the RBC:plasma lactate ratio, suggests that given an incremental work rate increase of 30 W, 1 min is adequate for equilibration of lactate between the plasma and RBCs. Also, under the conditions of this investigation, neither blood fraction analyzed nor exercise protocol had any effect on estimations of LT (in terms of VO2) by the Visual and Log-Log methods. However, LT determined by a fixed [La] of 2 mM may underestimate LT when plasma samples are used.


[Transcutaneous measurements of pO2 in newborns with RDS (author's transl)].
pO2 was measured transcutaneously (commercially available Clark Electrode, Bioelectronics Roche) with two different electrode temperatures in new born infants. The correlation between paO2 (arteria radialis) and ptcO2 was bad (r= 0,74) with electrode temperature of 42 degrees C. When the electrode was heated to 44 degrees C there was a very good correlation (r= 0,969) in 80 simultaneous measurements of paO2 (umbilical arterial catheter) and ptcO2. The mean values and standard deviations of pO2 values in hypoxic, normoxic and hyperoxic states are very similar: hypoxic: paO2 34,3 "/- 7,9, ptcO2 35,2 +/- 14,0, normoxic: paO2 78,7 +/- 14,3 ptcO2 78,8 +/- 16,7, hyperoxic: paO2 141,8 +/- 37,1, ptcO2 134,4 +/- 40,8 mmHg). The specific advantage of transcutaneous measurements is the trend registration for hours. With electrodes temperatures of 44 degrees C however, there is a risk of superficial burns if the electrode is attached to the identical site for 6 hours or more.


Multi-Year Leaf-Level Response to Sub-Ambient and Elevated Experimental CO2 in Betula nana.
The strong link between stomatal frequency and CO2 in woody plants is key for understanding past CO2 dynamics, predicting future change, and evaluating the significant role of vegetation in the hydrological cycle. Experimental validation is required to evaluate the long-term adaptive leaf response of C3 plants to CO2 conditions; however, studies to date have only focused on short-term single-season experiments and may not capture (1) the full ontogeny of leaves to experimental CO2 exposure or (2) the true adjustment of structural stomatal properties to CO2, which we postulate is likely to occur over several growing seasons. We conducted controlled growth chamber experiments at 150 ppmv, 450 ppmv and 800 ppmv CO2 with woody C3 shrub Betula nana (dwarf birch) over two successive annual growing seasons and evaluated the structural stomatal response to atmospheric CO2 conditions. We find that while some adjustment of leaf morphological and stomatal parameters occurred in the first growing season where plants are exposed to experimental CO2 conditions, amplified adjustment of non-plastic stomatal properties such as stomatal conductance occurred in the second year of experimental CO2 exposure. We postulate that the species response limit to CO2 of B. nana may occur around 400-450 ppmv. Our findings strongly support the necessity for multi-annual experiments in C3 perennials in order to evaluate the effects of environmental conditions and provide a likely explanation of the contradictory results between historical and palaeobotanical records and experimental data.


Oxytocin and enhancement of the positive valence of social affiliation memories: an autobiographical memory study.
Intranasal oxytocin has been shown to alter self-perceptions of personality (e.g., more trusting, increased extraversion). To follow up these findings, we examined the acute effects of two doses of intranasal oxytocin (24 IU and 48 IU) on another form of self-referential cognition: autobiographical memory. Changes in autobiographical memory (personal memories for the past) could conceivably effect change in self-perception and consequently alter social behaviors. We predicted that oxytocin would increase the number of specific personal memories recalled, and promote the recall of positive social affiliation memories. Seventeen male participants self-administered a placebo or oxytocin (24 IU, 48 IU) using a nasal spray on three separate occasions in a placebo-controlled, double-blind, and within-subject experiment. Participants completed the Autobiographical Memory Test (AMT) 110 minutes later. Analyses revealed a quadratic dose-response curve for the effects of intranasal oxytocin on autobiographical memory recall. The 24 IU dose, relative to the 48 IU dose and placebo, increased the number of specific personal memories recalled and promoted the recall of social affiliation memories that were rated more positively. The lack of effect with the 48 IU dose could be due to saturation of the oxytocin receptors at higher doses. Changes in autobiographical memory may be one mechanism by which oxytocin alters prosocial worldviews.


Observation of pyridine aggregation in aqueous solution using neutron scattering experiments and MD simulations.
Neutron diffraction with isotopic substitution (NDIS) experiments have been used to examine the structuring of aqueous solutions of pyridine. A new method is described for extracting the structure factors relating to intermolecular correlations from neutron scattering experiments on liquid solutions of complex molecular species. This approach performs experiments at different concentrations and exploits the intramolecular coordination number concentration invariance (ICNCI) to separate the internal and intermolecular contributions to the total intensities. The ability of this method to deconvolute molecular and intermolecular correlations is tested and demonstrated using simulated neutron scattering results predicted from molecular dynamics simulations of aqueous solutions of the polyatomic solute pyridine in which the inter- and intramolecular terms are known. The method is then implemented using neutron scattering measurements on solutions of pyridine. The results confirm that pyridine shows a significant propensity to aggregate in solution and demonstrate the prospects for the future application of the ICNCI approach to the study of large polyatomic solutes using next-generation neutron sources and detectors.


The interaction between vigabatrin and diazepam on the electroencephalogram during active behaviour in rats: an isobolic analysis.
To test whether polytherapy with two gamma-aminobutyric acid (GABA) -ergic drugs might be clinically relevant for epilepsy treatment, effects on spike and wave discharges, the fraction of time spent being behaviourally active, and the background electroencephalogram (EEG) during behavioural activity of vigabatrin (15-500 mg/kg i.p.) and diazepam (1.25-10 mg/kg i.p.) were compared with their combination (dose ratio 1:25) in rats. Isobolic analyses were performed to describe the interactions. Unfortunately, no conclusions can be drawn concerning the interaction of both drugs on the spike and wave discharge activity because the effect of diazepam was shown to be dominant. Only vigabatrin decreased the behavioural activity, whereas there was a trend towards a decrease after diazepam. All treatments dose dependently increased the power in the beta frequency band. Unfortunately, the dose ratio was not optimal to describe the interaction. The theta peak frequency was dose dependently decreased after all treatments. There was a synergistic interaction between the two drugs on this variable. These data support both the idea that an increase in power in the beta frequency band can serve as a biomarker for GABAergic inhibition and the suggestion that clinically effective anxiolytics decrease the theta peak frequency. Furthermore, we show that on different variables, there might be different optimal dosage combinations, which might complicate the clinical application of polytherapy.


Can Nonoffending Pedophiles Be Reached for the Primary Prevention of Child Sexual Abuse by Addressing Nonoffending Individuals Who Are Attracted to Minors in the United States? New Strategies With The Global Prevention Project.
This paper introduces a new prevention strategy against child sexual abuse (both offline and online) in the United States. The Global Prevention Project is a supportive treatment program designed for nonoffending minor-attracted persons who reside in the community. Attraction to minors and the underlying scientific terms (pedophilia/hebephilia) are discussed and a framework is provided for how to implement such a program in the United States. Our treatment modality is described to provide transparency in our clinical work. We discuss challenges encountered in this domain with possible solutions and the legal ramifications of preventing child sexual abuse behaviors by targeting nonoffending individuals.


Identification and expression of a novel marsupial cathelicidin from the tammar wallaby (Macropus eugenii).
Cathelicidins are important components of the innate immune system and have been identified in skin and epithelia of a range of mammals. In this study molecular techniques, including RACE-PCR, were used to identify the full cDNA sequence of a cathelicidin gene, MaeuCath8, from the Australian marsupial, the tammar wallaby, Macropus eugenii. This cathelicidin was not homologous to other such genes previously isolated from a tammar wallaby mammary gland EST library, however, it did contain 4 conserved cysteine residues which characterise the pre-propeptide and had 80% identity with a previously isolated bandicoot cathelicidin. Reverse transcriptase-PCR established the expression profile of MaeuCath8 in a range of tissues, including spleen, thymus, gastrointestinal tract, skin and liver, of the tammar wallaby from birth to adulthood. Expression of MaeuCath8 was observed in spleen and gastrointestinal tract of newborn animals and was observed in most tissues by 7 days post-partum. The results indicate that pouch young could synthesize their own antimicrobial peptides from an early age suggesting that this ability most likely plays a role in protecting the pouch young from infection prior to the development of immunocompetence.


Physical activity promotion and obesity prevention in Girl Scouts: Scouting Nutrition and Activity Program+.
A previous version of Scouting Nutrition and Activity Program (SNAP) resulted in greater physical activity (PA) during troop meetings, but no impact on girls' body mass index (BMI) or overall PA. The purpose of this study was to evaluate the effects of a 6-month intervention that coupled the evidence-based program SNAP with a channel of communication to parents using health report cards. Thirty-two Girl Scouts (mean age = 9.5, SD = 1.4 years) received the SNAP+ intervention. Girls were measured before and after the intervention on body composition, BMI, and 7-day step counts. Troop leaders were trained to implement an interactive obesity-prevention curriculum. Parents received health report cards designed to provide personalized information about their daughters' PA and weight status. The full sample of participants took more steps per day after the intervention (mean difference = 1741, P= 0.007). Results showed that lower values for body fat percentage (P= 0.620), BMI percentile (P= 0.100) and BMI z-scores (P= 0.055) at intervention end were not statistically significant. In the subsample of girls at risk for overweight and obesity, there were lower values for BMI z-score (P= 0.010), BMI percentile (P= 0.027), and body fat percentage (P= 0.053). From this preliminary study, the SNAP+ intervention appears to be effective for Scout-based promotion of PA, and for the prevention of overweight and obesity in at-risk Girl Scouts, but further evaluation through a fully powered randomized controlled trial is warranted.


Application of Blurred Image Processing and IoT Action Recognition in Sports Dance Sports Training.
In order to process the blurred image, this study proposes to combine the blurred point functions in the invariant space into multiple blurred images and then restore them through the deconvolution operation. The PSF functions of the fuzzy invariant space are combined to obtain the fuzzy invariant space. Finally, a gradual restoration method is used to perform many blurred image processing steps. The experimental results prove that the method proposed in this study can avoid the noise introduced in the process of multiple deconvolutions, can reduce the calculation error, and can improve the recovery effect. Based on fuzzy image processing, this research studies the nature of human motion and the identification of actions in the Internet of Things, which provides new ideas and methods for recognition research. The Kinect somatosensory camera of the Internet of Things is used to capture deep images, and 20 three-dimensional points of the human skeleton structure are obtained through its SDK. Based on this, the motion characteristics of human joints were studied, and a motion resolution model suitable for the Internet of Things was proposed. The model has low complexity, simple calculation, and sorting characteristics. Based on this, this research study also uses software engineering ideas and general methods of system development to design and create sports dance management information systems and uses advanced methods such as computers and the Internet to maintain training management to achieve optimal sports training for sports dance mode and to provide information about the management of sports dance athletes training to improve efficiency and the management level.


Effect of maternal smoking on colostrum and breast milk cytokines.
Breast milk contains several immune modulator components. The transfer of numerous cytokines via mother's milk may add to an active stimulation of the infant's immune system. There are many factors in breast milk that could either facilitate or inhibit cytokine activities. Smoking negatively influences the immune system and changes the concentrations of important cytokines. The objective of this study was to assess the effect of smoking during pregnancy on the cytokines found in colostrum and mature human milk. The study population included 25 smoker and 27 non-smoker nursing mothers who gave birth to a term healthy infant via cesarean section. Breast milk was collected from the mothers on the 2(nd)-3(rd) and 21(st)-25(th) days postpartum during visits to examine the newborns. Samples were analyzed for IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α and TNF-β cytokines by flow cytometric bead array. We first saw that concentrations of IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α, and TNF-β cytokines, but not IL-12, were measurable both in colostrum and in mature milk, being higher in colostrum. Next we observed that IL-1β and IL-8 levels were significantly lower in colostrum, and IL-6 was found to be significantly lower in the mature milk of smoking mothers. No significant effects of maternal smoking on breast milk concentrations of IL-2, IL-4, IL-5, IL-10, IFN-γ, TNF-α, and TNF-β were observed. These findings indicate that maternal smoking alters the colostrum and mature milk levels of some cytokines. Therefore, it is thought that active smoking during pregnancy decreases the concentration of certain cytokines in breast milk, which might account for the newborn's increased susceptibility to infections.


[Differential Diagnosis of Erythrocytosis - Background and Clinical Relevance].
Due to its rare incidence, erythrocytosis frequently represents a challenge for the treating doctors. The erythropoiesis (= production of erythrocytes) is located in the bone marrow, and the hormone erythropoietin (EPO) takes control in its regulation. Therefore, measurement of EPO in serum is one of the main diagnostic steps. In erythrocytosis, congenital causes have to be distinguished from acquired ones. Furthermore, there are primary and secondary forms. Congenital causes of erythrocytoses occur very infrequently, are mainly diagnosed in young age and should be treated in specialized centers. Polycythemia vera (PV), a clonal disorder and one of the main myeloproliferative neoplasms (beside essential thrombocythemia and primary myelofibrosis), represents the most frequent primary acquired cause of erythrocytosis. Clinically, increased thrombophilia and microvascular disturbance occur. The first-line treatment in patients with PV includes administration of aspirin and phlebotomies. Secondary acquired forms of erythrocytosis mainly occur due to hypoxia triggered by nicotine abuse or chronic heart and lung diseases. Regarding other differential diagnoses, a cancer-associated EPO production, kidney diseases or exogenous supply with EPO (= EPO doping) have to be considered.


Joint Effects: A Pilot Investigation of the Impact of Bipolar Disorder and Marijuana Use on Cognitive Function and Mood.
Marijuana is the most widely used illicit substance in those diagnosed with bipolar I disorder. However, there is conflicting evidence as to whether marijuana may alleviate or exacerbate mood symptomatology. As bipolar disorder and marijuana use are individually associated with cognitive impairment, it also remains unclear whether there is an additive effect on cognition when bipolar patients use marijuana. The current study aimed to determine the impact of marijuana on mood in bipolar patients and to examine whether marijuana confers an additional negative impact on cognitive function. Twelve patients with bipolar disorder who smoke marijuana (MJBP), 18 bipolar patients who do not smoke (BP), 23 marijuana smokers without other Axis 1 pathology (MJ), and 21 healthy controls (HC) completed a neuropsychological battery. Further, using ecological momentary assessment, participants rated their mood three times daily as well as after each instance of marijuana use over a four-week period. Results revealed that although the MJ, BP, and MJBP groups each exhibited some degree of cognitive impairment relative to HCs, no significant differences between the BP and MJBP groups were apparent, providing no evidence of an additive negative impact of BPD and MJ use on cognition. Additionally, ecological momentary assessment analyses indicated alleviation of mood symptoms in the MJBP group after marijuana use; MJBP participants experienced a substantial decrease in a composite measure of mood symptoms. Findings suggest that for some bipolar patients, marijuana may result in partial alleviation of clinical symptoms. Moreover, this improvement is not at the expense of additional cognitive impairment.


[Influence of adrenoreceptors on functions of the body].
The remarkably diverse effects of the catecholamines and similar sympathomimetic agents are directly related to an understanding of the classification and different types of adrenoreceptors. Characteristics and physiological regulatory mechanisms of the receptor result in variable response of organ systems to catecholamines stimulation. Different adrenoreceptors regulate distinct physiological processes by controlling the synthesis or release of a variety of second messengers. The goal of this review was to turn one's attention to the below mentioned aspects. There are three known subtypes of each alpha1-, alpha2- and beta-adrenoreceptor types. Structure of the adrenoreceptors, which belong to subtypes of the same receptor type, is similar and structure of the adrenoreceptors of the separate types is very different. Genetic peculiarities of the receptors may influence liability to some diseases. Acting on the adrenoreceptors may change function of many organs and may serve for the treatment of cardiovascular, respiratory tract diseases and allergic reactions. Selective acting on the adrenoreceptors of the separate subtypes may have the different effect on the organs. Great consideration is given for that property in the development of new drugs: substitution by different chemical radicals leads to increasing selectivity for the separate subtypes of the adrenoreceptors. The prolonged use of the adrenomimetics may lead to refractoriness.


AQP8 and AQP9 expression in patients with polycystic ovary syndrome and its association with in vitro fertilization-embryo transfer outcomes.
The aim of the present study was to investigate aquaporin (AQP)8 and AQP9 expression in patients with polycystic ovary syndrome (PCOS) and its association with in vitro fertilization-embryo transfer (IVF-ET) outcomes. A total of 45 patients with PCOS undergoing IVF-ET (test group) and 50 patients with oviduct obstruction or ovarian cyst (control group) were assessed for the mRNA expression of AQP8 and AQP9 in ovarian tissues by reverse transcription-quantitative (RT-q)PCR. The levels of luteinizing hormone, anti-mullerian hormone and testosterone were determined, which were revealed to be significantly different between the two groups (P<0.05). The RT-qPCR results indicated that AQP8 expression in the control group was lower than that in the test group (t=37.75, P<0.01), whereas AQP9 expression in the control group was higher than that in the test group (t=19.59, P<0.01). The number of eggs obtained in the group with high AQP8 expression was significantly lower than that in the group with low AQP8 expression (t=2.64, P<0.01). The number of high-quality embryos in the high AQP8 expression group was not significantly different from that in the low AQP8 expression group (t=1.02, P>0.05). The pregnancy rate in patients with high AQP9 expression was higher than that in the low AQP9 expression group (P<0.05) and the abortion rate in the former was lower than that in the latter (P<0.05). In conclusion, AQP8 and AQP9 are differentially expressed in ovarian tissues of patients with PCOS vs. normal control subjects. The expression of AQP8 is closely associated with the occurrence and development of oocytes, whereas the expression of AQP9 is associated with the success rate of pregnancy in patients with PCOS.


Autonomy as Ideology: Towards an Autonomy Worthy of Respect.
Recent criticism of the role of respect for autonomy in bioethics has focused on that principle's status as 'dogma' or 'ideology'. I suggest that lying beneath many applications of respect for autonomy in medical ethics are some influential dogmas — propositions accepted, not as explicit premises or as a consequence of reasoned argument, but simply because moral problems are so frequently framed in such terms. Furthermore, I will argue that rejecting these dogmas is vital to secure and protect an autonomy worthy of respect. The concept of autonomy that is widely applied in clinical ethics emphasises decision-making competence, at the expense of considering the authenticity of those decisions. Respect for such autonomy is interpreted in largely synchronic and individual terms — concerned with the isolated decisions of individual agents — and thus neglects the diachronic and social dimensions of many moral dilemmas arising in the health care context. I will examine how these unwritten rules lead to an impoverished understanding of respect and a systematic neglect in bioethics of certain kinds of ethical consideration, and draw on insights from feminist and communitarian work on autonomy to sketch an alternative approach to understanding respect, modelled on the norms of respectful conversation — a respect that is firstly concerned with engaging with the another as a potential giver and bearer or reasons, and working with them to promote both individual and social flourishing.


Interobserver variation of single-photon emission computed tomography bone scans in patients evaluated for unilateral condylar hyperactivity.
This study assessed the quantitative evaluation of the region of interest (ROI) by mean and maximum pixel counts of single-photon emission computed tomography (SPECT) scans in patients with clinical suspicion of unilateral condylar hyperactivity (UCH); the interobserver reliability and the correlation of condylar activity with patient age was determined. Two independent observers analyzed 67 bone SPECT scans. Maximum and mean activity values within an ROI on the mandibular condyle were analyzed; a cutoff value of 55% was used to determine the qualitative outcome. Excellent interobserver agreement was seen for both maximum (kappa 1.0) and mean activity analysis (kappa 0.94). Maximum and mean condylar activities were strongly correlated (r > 0.98). Maximum and mean condylar activity of the normal condyle decreased significantly with increasing age. Maximum and mean condylar activity levels were highly correlated in patients with mandibular asymmetry. An excellent interobserver agreement was found with either maximum or mean condylar activity.


Pokemon expression in malignant glioma: an application of bioinformatics methods.
In this report the authors review the role of bioinformatics in the design of a research project in which the molecular genetics of malignant glioma were studied. A project to characterize Pokemon expression in malignant glioma was developed, refined, and implemented using bioinformatics methods. Using the resources available from the National Center for Biotechnology Information, the messenger RNA (mRNA) sequence for Pokemon was determined. With this information and online primer design tools, novel primers were designed that would specifically amplify Pokemon mRNA by using reverse transcription-polymerase chain reaction assays. The promise of bioinformatics is in the rapid and widespread dissemination and analysis of genomic information. This information is then used in research investigating the genetic basis of disease. In this paper the authors review the bioinformatics methods used in their study of Pokemon expression in malignant glioma.


Inhibition of HIV-1 IIIB and clinical isolates by human parotid, submandibular, sublingual and palatine saliva.
Human saliva is known to possess components that decrease the HIV-1 infectivity in vitro. The mechanism of how these components inhibit the infectivity is still not clear on the molecular level. The purpose of this study was to discriminate between serous and mucous components with respect to inhibitory capacity and site of action. We have used total saliva and saliva from the major (sero)mucous glands: submandibular gland, sublingual glands, and glands in the palate, in comparison with the serous parotid glands. HIV-1 IIIB and primary variants were incubated with saliva, and inhibition of HIV-1-infection was determined by analysing the cytopathic effect on MT-2 cells. Mucous saliva, as well as serous saliva, contained high molecular weight components that reduced HIV-1-infectivity, at least partially by entrapment of the virus particles. Lower molecular weight components in all types of saliva possessed strong HIV-1 neutralizing capacity. Using pro-viral DNA synthesis by reverse transcription as a discrimination point in the replication cycle, the results indicated that part of the saliva samples acted before, but others after, this point. In conclusion, saliva inhibits HIV-1-infection by the action of high molecular weight components in combination with low molecular weight components from serous as well as mucous saliva, affecting different stages of the infection cycle.


Healthcare worker's emotions, perceived stressors and coping mechanisms during the COVID-19 pandemic.
Increasing cases, insufficient amount of personal protection equipment, extremely demanding workloads, and lack of adequate therapies to save lives can contribute to a psychological burden directly related to working during disease outbreaks. Healthcare workers (HCWs) are at a high risk of contracting COVID-19 due to its ability to spread efficiently through asymptomatic and symptomatic individuals. There are limited studies assessing the pandemic's psychological impact on HCWs, specifically those in close proximity to hospitalized patients with COVID-19. Our study explored the emotions, perceived stressors, and coping strategies of front-line HCWs at high risk of exposure to COVID-19 during the first surge at our community-based teaching hospital, the epicenter of COVID-19 in Connecticut. A validated comprehensive questionnaire derived and modified from previous epidemics was used to inquire about staff feelings, factors that caused stress and factors that mitigated stress. Personal coping strategies and factors that can increase staff's motivation to work during future events of similar nature were also asked. Emotional reactions, coping mechanisms, and stressors varied by healthcare role, while some experiences and reactions were similar among groups. Willingness to participate in a second wave of the pandemic or future outbreaks is strongly driven by adequate personal protective equipment, financial recognition, and recognition from management, similarly reported in previous disease outbreaks. All groups felt a reduction in stress due to a sense of camaraderie and teamwork, as well as when sharing jokes or humor with colleagues. Our HCWs at high risk of exposure experienced significant emotional distress during the first wave of the COVID-19 pandemic. By understanding the needs and experiences of our HCWs at highest risk, we can improve our psychological support using targeted interventions during future waves of this pandemic or similar devastating events.


Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation.
Acetaminophen is widely used for pain management as an alternative to NSAIDs and selective COX-2 inhibitors, but its action at a molecular level is still unclear. We evaluated acetaminophen's effect on PG release and the expression patterns of genes related to PG production in a clinical model of tissue injury and acute inflammation. Subjects (119 outpatients) received either 1000 mg acetaminophen, 50 mg rofecoxib (a selective COX-2 inhibitor), 30 mg ketorolac (a dual COX-1/COX-2 inhibitor), or placebo before the surgical removal of two impacted mandibular third molars. Microdialysis was used to collect inflammatory transudate from the surgical site for measurement of PGE2 and TXB2 levels at the site of injury. Biopsies were collected to investigate the expression patterns of genes related to PG production at baseline prior to surgery and at 3 or 24 h following surgery. PGE2 release was suppressed by ketorolac, rofecoxib and acetaminophen compared to placebo at 3 h coincident with increased COX-2 gene expression in biopsies collected from the surgical site. TXB2 release was suppressed only by ketorolac. COX-2 gene expression remained elevated at 24 h with continued ketorolac and acetaminophen treatment. COX-1 gene expression was significantly down-regulated at 24 h by ketorolac, rofecoxib and acetaminophen. Acetaminophen suppression of PGE2 without inhibiting TXB2 release, when COX-2 gene expression is up-regulated, suggests that acetaminophen is a selective COX-2 inhibitor in vivo. The up-regulation of COX-2 gene and down-regulation of COX-1 gene expression suggests that acetaminophen may result in changes in COX-derived prostanoids with repeated doses.


[Neurosurgery of the spasticity syndrome in children cerebral palsy].
The review is devoted to main neurosurgical approaches to the treatment of the spasticity syndrome in children cerebral palsy. Neurosurgical procedures are divided into destructive and neuromodulating. The former included posterior selective rhizotomy, selective neurotomy and destructive operations on subcortical brain structures. The latter group included electrostimulation of brain and spinal cord structures and implantation of pumps for the chronic intrathecal baclofen (lioresal) infusion. Each method is considered in a historical aspect. Details of clinical application, positive and negative sides of the methods are described.


[Molecular Target Therapy for Soft Tissue Sarcoma].
Soft tissue sarcoma(STS)is one of the rare and intractable cancers, and most types of STS are not sensitive to chemotherapy. Development of specific molecular target therapy for each type of STS is necessary. There are specific chromosome translocations in 20-30% of STS, but their products are mostly transcriptional factors, and target therapy for those factors are difficult to develop. Trabectedin is an alkylating agent and is also inhibit function of transcriptional factors, and shows efficacy for translocation-related sarcoma(TRS)such as myxoid liposarcoma. As molecular target therapies for gene mutations, success in molecular target therapy for c-kit and PDGFR mutation in GIST was followed by efficacy for rare sarcomas such as IMT or DFSP, but there are few developments in other sarcomas. STSs are frequently associated with angiogenesis and angiogenesis inhibitors such as pazopanib show some efficacy. Then immune checkpoint inhibitors also have been developed.


A redox-sensitive cysteine in Zta is required for Epstein-Barr virus lytic cycle DNA replication.
Epstein-Barr virus (EBV) reactivation from latency is known to be sensitive to redox regulation. The immediate-early protein Zta is a member of the basic-leucine zipper (bZIP) family of DNA binding proteins that stimulates viral and cellular transcription and nucleates a replication complex at the viral lytic origin. Zta shares with several members of the bZIP family a conserved cysteine residue (C189) that confers redox regulation of DNA binding. In this work, we show that replacement of C189 with serine (C189S) eliminated lytic cycle DNA replication function of Zta. The mechanistic basis for this replication defect was investigated. We show that C189S was not significantly altered for DNA binding activity in vitro or in vivo. We also show that C189S was not defective for transcription activation of EBV early gene promoters. C189S was deficient for transcription activation of several viral late genes that depend on lytic replication and therefore was consistent with a primary defect of C189S in activating lytic replication. C189S was not defective in binding methylated DNA binding sites and was capable of activating Rta from endogenous latent viral genomes, in contrast to the previously characterized S186A mutation. C189S was slightly impaired for its ability to form a stable complex with Rta, although this did not prevent Rta recruitment to OriLyt. C189S did provide some resistance to oxidation and nitrosylation, which potently inhibit Zta DNA binding activity in vitro. Interestingly, this redox sensitivity was not strictly dependent on C189S but involved additional cysteine residues in Zta. These results provide evidence that the conserved cysteine in the bZIP domain of Zta plays a primary role in EBV lytic cycle DNA replication.


Abuse and victimization: a life-span developmental perspective.
A conceptualization of coping and adaptation following victimization is presented from a life-span developmental perspective. Recovery is characterized as an evolving process of interaction among three dimensions: social cognition, environmental sensitivity, and emotional-behavioral functioning. The model is illustrated through an individual case study and through an approach to research on outcomes of sexual victimization.


MRI in detection of hepatocellular carcinoma (HCC).
Hepatocellular carcinoma (HCC) is the commonest malignancy of the liver and is usually due to cirrhosis. Early detection of HCC and the premalignant dysplastic nodules has implications on the management options of tumor ablation, liver resection and transplantation. Magnetic resonance imaging is useful for the detection and characterization of lesions, in the identification of dysplastic nodules and their malignant transformation into HCC.


A lin-45 raf enhancer screen identifies eor-1, eor-2 and unusual alleles of Ras pathway genes in Caenorhabditis elegans.
In Caenorhabditis elegans, the Ras/Raf/MEK/ERK signal transduction pathway controls multiple processes including excretory system development, P12 fate specification, and vulval cell fate specification. To identify positive regulators of Ras signaling, we conducted a genetic screen for mutations that enhance the excretory system and egg-laying defects of hypomorphic lin-45 raf mutants. This screen identified unusual alleles of several known Ras pathway genes, including a mutation removing the second SH3 domain of the sem-5/Grb2 adaptor, a temperature-sensitive mutation in the helical hairpin of let-341/Sos, a gain-of-function mutation affecting a potential phosphorylation site of the lin-1 Ets domain transcription factor, a dominant-negative allele of ksr-1, and hypomorphic alleles of sur-6/PP2A-B, sur-2/Mediator, and lin-25. In addition, this screen identified multiple alleles of two newly identified genes, eor-1 and eor-2, that play a relatively weak role in vulval fate specification but positively regulate Ras signaling during excretory system development and P12 fate specification. The spectrum of identified mutations argues strongly for the specificity of the enhancer screen and for a close involvement of eor-1 and eor-2 in Ras signaling.


Effect of D-glucitol-hexanicotinate on platelet aggregability in patients with coronary heart disease.
D-glucitol-hexanicotinate (sorbinicate) was administered at a daily dose of 1.6 mg to 16 male patients who had survived myocardial infarction. Platelet aggregation induced by collagen (5 micrograms/ml), by ADP (2, 1.2, 0.8, and 0.4 X 10(-6)M), and by epinephrine (1 and 0.5 X 10(-6)M) was significantly decreased after 3 months of therapy. In a group of 13 comparable patients, who did not receive sorbinicate, platelet aggregation induced by ADP (1.2, 0.8, and 0.4 X 10(-6)M) and by epinephrine (1 X 10(-5)M and 1 X 10(-6)M) was significantly increased 3 months after entry into the study. Sorbinicate has effective lipid-lowering activity; the combination of hypolipidemic and anti-aggregating properties may prove important in primary and secondary prevention of atherosclerotic disease.


Estimation of copy number using SYBR Green: confounding by AT-rich DNA and by variation in amplicon length.
Although SYBR Green is used to estimate copy number, its fluorescence varies with amplicon length and adenine/thymine (AT) content. As a result, threshold cycle (Ct) values obtained using real-time polymerase chain reaction (PCR) are lower for longer amplicons (P<0.001) and amplicons with greater AT content (P<0.001). In contrast, neither amplicon length nor AT content affects the Ct with TaqMan probes or LUX-labeled primers. Because SYBR Green yields lower Cts with AT-rich templates and longer templates, it overestimates copy number for those templates. Therefore, sequence-specific methods such as TaqMan probes or LUX-labeled primers should be considered when using real-time PCR to estimate copy number if the amplicons generated are AT-rich or vary in length.


Distinct genetic origins of eumelanin intensity and barring patterns in cichlid fishes.
Pigment patterns are incredibly diverse across vertebrates and are shaped by multiple selective pressures from predator avoidance to mate choice. A common pattern across fishes, but for which we know little about the underlying mechanisms, is repeated melanic vertical bars. In order to understand genetic factors that modify the level or pattern of vertical barring, we generated a genetic cross of 322 F2 hybrids between two cichlid species with distinct barring patterns, Aulonocara koningsi and Metriaclima mbenjii. We identify 48 significant quantitative trait loci that underlie a series of seven phenotypes related to the relative pigmentation intensity, and four traits related to patterning of the vertical bars. We find that genomic regions that generate variation in the level of eumelanin produced are largely independent of those that control the spacing of vertical bars. Candidate genes within these intervals include novel genes and those newly-associated with vertical bars, which could affect melanophore survival, fate decisions, pigment biosynthesis, and pigment distribution. Together, this work provides insights into the regulation of pigment diversity, with direct implications for an animal's fitness and the speciation process.


Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression.
The expression of microRNA in nonalcoholic steatohepatitis (NASH) and their role in the genesis of NASH are not known. The aims of this study were to: (1) identify differentially expressed microRNAs in human NASH, (2) tabulate their potential targets, and (3) define the effect of a specific differentially expressed microRNA, miR-122, on its targets and compare these effects with the pattern of expression of these targets in human NASH. The expression of 474 human microRNAs was compared in subjects with the metabolic syndrome and NASH versus controls with normal liver histology. Differentially expressed microRNAs were identified by the muParaflo microRNA microarray assay and validated using quantitative real-time polymerase chain reaction (PCR). The effects of a specific differentially expressed miRNA (miR-122) on its predicted targets were assessed by silencing and overexpressing miR-122 in vitro. A total of 23 microRNAs were underexpressed or overexpressed. The predicted targets of these microRNAs are known to affect cell proliferation, protein translation, apoptosis, inflammation, oxidative stress, and metabolism. The miR-122 level was significantly decreased in subjects with NASH (63% by real-time PCR, P < 0.00001). Silencing miR-122 led to an initial increase in mRNA levels of these targets (P < 0.05 for all) followed by a decrease by 48 hours. This was accompanied by an increase in protein levels of these targets (P < 0.05 for all). Overexpression of miR-122 led to a significant decrease in protein levels of these targets. NASH is associated with altered hepatic microRNA expression. Underexpression of miR-122 potentially contributes to altered lipid metabolism implicated in the pathogenesis of NASH.


Detection of a novel missense mutations in atrichia with papular lesions.
Atrichia with papular lesions (APL) is a rare inherited disease characterized by early onset of total hair loss, followed by papular lesions over the extensor areas of the body. Recently, mutations in the human hairless (HR) gene have been implicated in its pathogenesis. The identification of mutations in the HR gene is important for differentiating between APL and alopecia universalis (AU). We compared the HR genes of patients with presumed AU who showed minimal or no response to treatment with the HR genes of healthy controls. The subjects were 11 patients with presumed AU who had not responded to treatments. Fifty healthy people were included as controls for molecular analysis. To screen for mutations, polymerase chain reaction was performed. DNA analysis identified a novel heterozygous G-to-A transition at nucleotide position 191 in exon 5. The mutation was not found in the controls, other AU patients, or any unaffected family members except for the patients' mother and maternal grandfather, who were heterozygous HR gene carriers. Our study identifies a novel missense mutation in exon 5 of the HR gene in a Korean APL patient previously diagnosed as AU.


miRNA as an Ultimate and Emerging Diagnostic Approach for the Detection of Alzheimer's Disease.
Alzheimer's disease is a prevalent neurodegenerative disorder primarily affecting elderly individuals, characterized by cognitive decline and dysfunction in the nervous system. The disease is hallmarked by the presence of neurofibrillary tangles and amyloid-β plaques. Approximately 10.7% of the global population aged 65 and above suffer from Alzheimer's disease, and this number is projected to rise significantly in the foreseeable future. By the year 2050, the worldwide prevalence is estimated to reach 139 million cases, compared to the current 55 million cases. The identification of reliable biomarkers that can facilitate the diagnosis and prognosis of Alzheimer's disease is crucial. MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that play a significant role in mRNA regulation and protein level maintenance through mRNA degradation. Over the past decade, researchers have primarily focused on elucidating the functions and expression patterns of miRNAs in various diseases, including Alzheimer's disease, to uncover their potential as diagnostic biomarkers. This review emphasizes the potential of miRNAs as diagnostic biomarkers for Alzheimer's disease and explores their roles and therapeutic possibilities. MiRNAs possess several features that make them ideal biomarkers, including their ability to be easily detected in body fluids. Moreover, the extraction process is minimally invasive, as miRNAs can be readily extracted. Advances in technology have facilitated the integration of miRNAs into micro-assays, enhancing the reliability and utility of miRNAs as diagnostic biomarkers for Alzheimer's disease.


Effect of targeted nursing applied to SLE patients.
The aim of the present study was to evaluate the efficacy of targeted nursing for patients with systemic lupus erythematosus (SLE). A total of 114 patients clinically diagnosed with stable SLE were prospectively selected. The patients were randomly divided into the regular special nursing group, comprising 56 patients and the targeted nursing group (i.e., taylor made according to different pathogenic conditions and treatment period), comprising 58 patients. The patients received standard medical treatment for SLE, irrespective of their group, and the efficacy of targeted nursing on disease activity, incidence of complications, therapeutic compliance, quality of life and nursing satisfaction was compared with regular special nursing. The patients were followed up for a period of 20 months. The results showed that, disease activity and injury index score and incidence of complications were significantly less in the targeted nursing group than in the regular special nursing group (P<0.05). Additionally, therapeutic compliance, quality of life score and nursing content satisfaction were significantly higher in the targeted nursing group in comparison with the regular special nursing group (P<0.05). Thus, the results indicated that targeted nursing significantly improved therapeutic compliance and quality of life, and simultaneously, reduced complications and disease activity in patients receiving standard treatment for SLE.


Association between single nucleotide polymorphisms of tumor necrosis factor gene and grade II-IV acute GvHD: a systematic review and meta-analysis.
Acute GvHD (aGvHD) complicates up to 50% of allogeneic hematopoietic cell transplants and pre-transplant estimation of its risk can guide prophylaxis, monitoring and early intervention strategies. Inspired by the role of tumor necrosis factor alpha (TNFα) in the pathogenesis of aGvHD and the inconsistency of the association studies exploring single nucleotide polymorphisms (SNPs) of the TNF gene, we conducted a systematic review and meta-analysis of the available reports using PubMed and EMBASE. Original human studies reporting on the association between recipient TNF SNPs and grade II-IV aGvHD in a format convertible to effect size and confidence interval were included. One of the two most widely investigated SNPs (rs361525G>A) was marginally associated with increased risk of grade II-IV aGvHD in random-effects meta-analysis of six studies (627 patients in total, risk ratio=1.29, 95% confidence interval=0.99-1.69, P=0.06). If this result is validated in a large cohort with uniform conditioning and GvHD prophylaxis, TNF rs361525G>A may become a useful tool for aGvHD risk estimation before the transplant.


Development of an enzyme-linked immunosorbent assay for detection of CDCP1 shed from the cell surface and present in colorectal cancer serum specimens.
CUB domain containing protein 1 (CDCP1) is a transmembrane protein involved in progression of several cancers. When located on the plasma membrane, full-length 135kDa CDCP1 can undergo proteolysis mediated by serine proteases that cleave after two adjacent amino acids (arginine 368 and lysine 369). This releases from the cell surface two 65kDa fragments, collectively termed ShE-CDCP1, that differ by one carboxyl terminal residue. To evaluate the function of CDCP1 and its potential utility as a cancer biomarker, in this study we developed an enzyme-linked immunosorbent assay (ELISA) to reliably and easily measure the concentration of ShE-CDCP1 in biological samples. Using a reference standard we demonstrate that the developed ELISA has a working range of 0.68-26.5ng/ml, and the limit of detection is 0.25ng/ml. It displays high intra-assay (repeatability) and high inter-assay (reproducibility) precision with all coefficients of variation ≤7%. The ELISA also displays high accuracy detecting ShE-CDCP1 levels at ≥94.8% of actual concentration using quality control samples. We employed the ELISA to measure the concentration of ShE-CDCP1 in human serum samples with our results suggesting that levels are significantly higher in serum of colorectal cancer patients compared with serum from individuals with benign conditions (p<0.05). Our data also suggest that colorectal cancer patients with stage II-IV disease have at least 50% higher serum levels of ShE-CDCP1 compared with stage I cases (p<0.05). We conclude that the developed ELISA is a suitable method to quantify ShE-CDCP1 concentration in human serum.


Cellular and pharmacologic aspects of drug resistance in acute myeloid leukemia.
Modern treatments and supportive care regimens for acute myeloid leukemia have produced some cures of what was once a uniformly fatal disease. To enhance the cure rate, intense efforts are now being put forth to understand the mechanisms of resistance to chemotherapeutic regimens that actually arise in clinical cases of acute myeloid leukemia, and to develop ways and means to circumvent such resistance. This review focuses on such efforts involving daunorubicin and cytarabine, the two most effective agents currently available for treatment of the disease. Most current published studies of daunorubicin have focused on detecting the classic form of multidrug resistance. For cytarabine, pharmacologically directed treatment approaches and enhancement of cytarabine leukemic cell kill by increasing the distribution of cells in S-phase and manipulating cellular cytarabine transport are currently under investigation.


Genetic polymorphism of glycine-rich beta-glycoprotein in the Italian population.
Genetic polymorphism of glycine-rich beta-glycoprotein (GBG) was studied in populations from northern and southern Italy, respectively. Gene frequencies were as follows: northern Italy (n = 431): GbS = 0.7675, GbF = 0.2049, GbS 0.7 = 0.0127, GbF1 = 0.0139; southern Italy (n = 161): GbS = 0.7050, GbF = 0.2360, GbS 0.7 = 0.0373, GbF1 = 0.0217. Comparison of these two populations with the Swiss population revealed a significant drift in gene frequencies from north to south. A new GBG phenotype, supposedly heterozygous, with a slow migrating F band and a regular S band in agarose electrophoresis was observed.


Size of plastic events in strained amorphous solids at finite temperatures.
We address the system-size dependence of plastic flow events when an amorphous solid is put under a fixed external strain rate at a finite temperature. For small system sizes at low strain rates and low temperatures the magnitude of plastic events grows with the system size. We explain, however, that this must be a finite-size effect; for larger systems there exist two crossover length scales xi{1} and xi{2}, the first determined by the elastic time scale and the second by the thermal energy scale. For systems of size L>>xi there must exist (L/xi){d} uncorrelated plastic events which occur simultaneously. We present a scaling theory that culminates with the dependence of the crossover scales on temperature and strain rate. Finally, we relate these findings to the temperature and size dependence of the stress fluctuations. We comment on the importance of these considerations for theories of elastoplasticity.


Physical Therapist Students' Perceptions from Performing Strength and Conditioning Training: Academic, Professional, and Clinical Benefits.
The purpose of this qualitative study was to assess the perceptions of Doctor of Physical Therapy (DPT) students in performing collegiate athletes' strength and conditioning training. Four DPT students with the Certified Strength and Conditioning Specialist (CSCS) credential voluntarily provided collegiate athletes strength and conditioning training. Students were interviewed to obtain their perceptions of how the experience impacted performance in DPT school and perceptions of anticipated future benefits. Seven themes emerged from interviews: improved communication skills, movement analysis experience, improved time management/organization, increased understanding of exercises, attention to psychosocial aspects, interprofessional experience, and improved performance in coursework. DPT students with the CSCS credential perceived benefits from performing strength and conditioning training outside the standard DPT curriculum.


Cholera vaccine: WHO position paper, August 2017 - Recommendations.
This article presents the World Health Organization's (WHO) recommendations on the use of cholera vaccines excerpted from the Cholera vaccines: WHO position paper, August 2017, published in the Weekly Epidemiological Record (Cholera vaccine, 2017) [1]. This position paper replaces the 2010 WHO position paper on cholera vaccines (Cholera vaccine, 2010) [2]. It incorporates the most recent evidence on cholera vaccination and provides revised recommendations on the target populations for cholera immunization. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of cholera vaccines were discussed by the Strategic Advisory Group of Experts (SAGE) in April 2017; evidence presented at these meetings can be accessed at: www.who.int/immunization/sage/meetings/2017/April/presentations_background_docs/en/.


[Ureteral multiplicity. Review of case records].
We present distribution by age, sex, clinical picture and clinical examination of 86 cases of renoureteral duplication and one of triplication of which 47 underwent surgical treatment. Intravenous urography provided direct evidence of the existence of duplication in 94%, indirect evidence in 100%, and it disclosed ipsi-or contralateral complications in 23%. Cystography demonstrated vesico ureteral reflux in 62%. Injection of contrast into the ectopic ureteral meatus, echography and gammagraphy provided data of interest in some cases. Accounts are given of indication for operation, approach, surgical procedures, direct of indirect complications, the association of this entity with other pathological conditions and of other procedures which have been described in the treatment of this anomaly.


JAK2 inhibitor blocks the inflammation and growth of esophageal squamous cell carcinoma in vitro through the JAK/STAT3 pathway.
Recent research indicates that the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway may play an important role in chronic inflammation which promotes cancer progression, yet the mechanism is not clear. The present study aimed to investigate the role of the JAK/STAT3 pathway in the growth and cancer-related inflammation (CRI) of esophageal squamous cell carcinoma (ESCC) by studying the crosstalk between the JAK/STAT3 pathway and nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2) which are important inflammatory factors associated with tumorigenesis. Cell growth and the cell cycle were assessed by CCK-8 assays and flow cytometry, respectively. The protein levels of STAT3, phosphorylated STAT3, VEGF, NF-κB p65, phosphorylated NF-κB p65 and COX-2 in ESCC cells following treatment with JAK2 inhibitor for 48 h or interleukin-6 (IL-6) for 24 h were detected. RT-PCR was performed to study the interaction among STAT3, NF-κB and COX-2 by transfection of siRNAs targeted at STAT3 and NF-κB. STAT3 was activated in 3 ESCC cell lines at different levels. Blocking the JAK/STAT3 pathway inhibited cancer growth through regulation of cell growth, cell cycle and angiogenesis. Likewise, abrogation of the JAK/STAT3 pathway decreased CRI by downregulating levels of NF-κB p65 phosphorylation, COX-2 and IL-6 concentration. In addition, CRI and cancer growth were accelerated by IL-6 through stimulation of the JAK/STAT3 and NF-κB p65 pathway. Moreover, STAT3 and NF-κB both regulated COX-2 as a downstream gene. The JAK/STAT3 pathway is an important pathway which links CRI and cancer growth through IL-6 and crosstalk with the NF-κB p65 subunit and COX-2. The STAT3 pathway could be a novel target both for cancer treatment and prevention in ESCC.


Genotypic diversity and phenotypic traits of Streptococcus mutans isolates and their relation to severity of early childhood caries.
Early childhood caries (ECC) is an aggressive condition that can affect teeth of young children. This study aimed to evaluate genotypic diversity and phenotypic traits of S. mutans isolated from dental biofilms of children with different caries status in comparison with caries free (CF) children. Streptococcus mutans strains were isolated from supragingival biofilm samples of CF, ECC and severe-ECC (S-ECC) children and genotyped by arbitrary-primer polymerase chain reaction - AP-PCR. S. mutans genotypes were tested for their ability to reduce the suspension pH through glycolysis, to tolerate extreme acid challenge and by their ability to form biofilm. Response variables were analyzed by ANOVA/Tukey or Kruskal-Wallis/Mann-Whitney tests at a 5% of significance. There was an increase in the prevalence of Streptococcus mutans in biofilms with the severity of dental caries. No differences in genotypic diversity and in acidogenicity of genotypes were found among CF, ECC and S-ECC children. S mutans strains with genotypes more characteristic for ECC and S-ECC children formed more biofilms than those identified in CF children. The strains isolated from S-ECC children were highly acid tolerant. Although S. mutans genotypic diversity was similar among the groups of children, phenotypic traits of S. mutans, especially the acid tolerance response, could explain the severity of early childhood caries.


Structural and functional aspects of Kupffer cells.
Methods are now available to characterize Kupffer cells both in vivo and in vitro. They can be isolated and purified from the liver and their functional activities studied in maintenance culture. Kupffer cells are not merely phagocytic cells or scavengers but they can also produce and secrete a variety of substances that can regulate the functions of other cells. They can also regulate the immune system and be directly cytotoxic to tumor cells and parasites. In the light of these reported functions, the clinical importance of Kupffer cells in a variety of liver diseases deserves to be better explored. Although the origin and cytokinetics of Kupffer cells, and specially their relation to the Mononuclear Phagocyte System (MPS), are still not completely understood, it has now become clear that Kupffer cells are not end-cells incapable of self-proliferation. Under various experimental conditions Kupffer cells have been shown to respond to activation by strong mitotic proliferation. On the other hand, bone marrow-derived cells can migrate to the liver under certain conditions and differentiate into liver macrophages, thus becoming Kupffer cells.