Physical inactivity associated with the risk of non-communicable diseases in Japanese working mothers with young children: A cross-sectional study in Nagano city, Japan.
Physical activity helps to prevent the development of chronic non-communicable diseases. However, childbearing generally reduces parents' level of physical activity, particularly in mothers. Therefore, mothers with young children generally have lower levels of physical activity and have a higher risk of developing non-communicable diseases. The aim of the present study was to examine this risk in Japanese working mothers with young children. A cross-sectional study was conducted in four nursery schools in Nagano city, Japan. All mothers were asked to complete a questionnaire regarding abnormal findings at their proximate annual medical examination, and were asked to record their normal physical activity. A total of 182 mothers completed the questionnaires, and 36 reported having abnormal findings (ABN group). Mothers in the ABN group were significantly older than those without abnormal findings (NOR; P=0.043). No significant differences in physical activity were observed between the two groups; however, mothers in the ABN group spent a significantly longer time sitting than those in the NOR group (P=0.028). Regarding socioeconomic characteristics, mothers in the ABN group had a significantly higher educational background (P=0.040) and a higher annual family income (P<0.001) compared with those in the NOR group, and significantly more mothers held full-time jobs (55.9 vs. 36.0%; P=0.005). Full-time working mothers typically had a significantly higher family income (P<0.001) and spent a significantly longer time sitting (P<0.001) compared with mothers in part-time and other work. Therefore, the results of the present study suggest that sedentary lifestyles, namely the amount of time spent sitting, may increase the risk of Japanese working mothers with young children developing non-communicable diseases.


Poly(U)-agarose affinity chromatography: specific, sensitivity selectivity, and affinity of binding.
These studies were done to determine four basic intrinsic properties of poly(U)-agarose affinity columns. Specificity of binding studies demonstrated that binding to these columns is highly specific with greater than 90% complementary binding and less than or equal to 3% noncomplementary binding. Sensitivity of binding studies indicated that a minimum sequence of 10 adenylates is required for detectable complementary binding. Selectivity of binding studies revealed that nonsequential adenylates in native RNAs and randomly distributed adenylates in synthetic poly(A)-poly(C) co-polymers did not bind to poly(U)-agarose affinity columns. Whereas, affinity of binding studies demonstrated that A=U complementary base pairing is independent of chain-lengths of greater than or equal to 25 adenylates and dependent of chain-lengths of less than 25 adenylates. Thus the data demonstrates that poly(U)-agarose affinity chromatography is scientifically sound and expedient for the detection and isolation of poly(A)-containing cellular and viral RNAs.


An integrated public health response to an outbreak of Murray Valley encephalitis virus infection during the 2022-2023 mosquito season in Victoria.
Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus known to cause infrequent yet substantial human outbreaks around the Murray Valley region of south-eastern Australia, resulting in significant mortality. The public health response to MVEV in Victoria in 2022-2023 included a climate informed pre-season risk assessment, and vector surveillance with mosquito trapping and laboratory testing for MVEV. Human cases were investigated to collect enhanced surveillance data, and human clinical samples were subject to serological and molecular testing algorithms to assess for co-circulating flaviviruses. Equine surveillance was carried out via enhanced investigation of cases of encephalitic illness. Integrated mosquito management and active health promotion were implemented throughout the season and in response to surveillance signals. Mosquito surveillance included a total of 3,186 individual trapping events between 1 July 2022 and 20 June 2023. MVEV was detected in mosquitoes on 48 occasions. From 2 January 2023 to 23 April 2023, 580 samples (sera and CSF) were tested for flaviviruses. Human surveillance detected 6 confirmed cases of MVEV infection and 2 cases of "flavivirus-unspecified." From 1 September 2022 to 30 May 2023, 88 horses with clinical signs consistent with flavivirus infection were tested, finding one probable and no confirmed cases of MVE. The expanded, climate-informed vector surveillance system in Victoria detected MVEV in mosquitoes in advance of human cases, acting as an effective early warning system. This informed a one-health oriented public health response including enhanced human, vector and animal surveillance, integrated mosquito management, and health promotion.


Lipomatous variant of angiomyofibroblastoma: a case report and review of the literature.
Angiomyofibroblastoma represents a rare, benign mesenchymal tumor with a predilection for the vulvovaginal region. Lipomatous change may occur but rarely comprises a substantial component of the lesion. There are only eight reports in the English language literature describing the lipomatous variant of this tumor. We describe a further lipomatous angiomyofibroblastoma that occurred on the labium majus of a 49-year-old woman. The histopathologic and immunohistochemical features are described, and the collective experience in the literature is reviewed.


Ethical Issues in Dysphagia Management.
Dysphagia management is complex and requires balancing individuals' preferences, quality of life, and medical consequences. Ethical challenges are not uncommon given the complexity of dysphagia. Professionals must engage in ethical reflection and shared decision-making when managing dysphagia. Recognizing one's own presuppositions and beliefs may be fundamental to ensuring an ethical approach. The goal of this article is to apply principles of ethics using hypothetical case studies of dysphagia. To this end, we will describe the challenges of working with the disorder of dysphagia; the influence of culture on decision-making about eating and feeding; the importance of information disclosure and respect for individuals' refusal of recommendations; and the interplay of ethical reflection, evidence, and clinical judgment when making complex dysphagia management decisions. These concepts should be kept in mind to ensure compassionate and competent care of the person with eating, drinking, or swallowing problems and their family caregivers.


Widespread distribution of deletions of the bgl operon in natural isolates of Escherichia coli.
A deletion that includes the bgl (beta-glucoside utilization) operon of Escherichia coli was originally detected in several rarely occurring natural isolates that utilize cellobiose. Here I show that bgl deletions are present in 95% of the Cel+ isolates obtained from diverse sources. They are also present in 29% of the Cel- strains in two different collections of natural isolates of E. coli. At least three versions of bgl deletions are present in E. coli populations. In the most common version approximately 8 kb of DNA around the bgl region of E. coli K12 is replaced by a specific 6.5-kb DNA fragment. In another version a deletion of similar length is not replaced by the same sequence. A third version involves deletion of approximately 14 kb without the replacement fragment being present. The distribution of these deletions suggests that the version 1 deletion occurred very early in the history of E coli. It also appears likely that there is selection for bgl deletions in Cel+ strains of E. coli. The presence of the version 1 deletion within distantly related phylogenetic groups of E. coli provides evidence for recombination within natural populations of E coli.


Generalized Quasilinear Approximation: Application to Zonal Jets.
Quasilinear theory is often utilized to approximate the dynamics of fluids exhibiting significant interactions between mean flows and eddies. We present a generalization of quasilinear theory to include dynamic mode interactions on the large scales. This generalized quasilinear (GQL) approximation is achieved by separating the state variables into large and small zonal scales via a spectral filter rather than by a decomposition into a formal mean and fluctuations. Nonlinear interactions involving only small zonal scales are then removed. The approximation is conservative and allows for scattering of energy between small-scale modes via the large scale (through nonlocal spectral interactions). We evaluate GQL for the paradigmatic problems of the driving of large-scale jets on a spherical surface and on the beta plane and show that it is accurate even for a small number of large-scale modes. As GQL is formally linear in the small zonal scales, it allows for the closure of the system and can be utilized in direct statistical simulation schemes that have proved an attractive alternative to direct numerical simulation for many geophysical and astrophysical problems.


Naloxone treatment prevents prenatal stress effects on peritoneal macrophage activity in mice offspring.
The present study analyzed the effects of maternal stress (PS) and/or naloxone treatment on the activity of peritoneal macrophage in male and female Swiss mice offspring. Pregnant female rats received a daily footshock (0.2 mA) and/or a naloxone injection from gestational day 15 to 19. Experiments were performed on postnatal day 30 on male and female pups. The following results were obtained in male offspring: (1) PS decreased both the index and the percentage of phagocytosis, this decrement being reversed by naloxone treatment, and (2) naloxone alone decreased the percentage of phagocytosis. The following results were obtained in female offspring: (1) PS decreased spontaneous and phorbol myristate acetate-induced macrophage oxidative burst, this decrement being reversed by naloxone pretreatment, and (2) PS decreased both the index and percentage of the phagocytosis, this effect was prevented by naloxone treatment. These data are discussed focussing on a putative neuroimmune interaction involving opioidergic systems during the ontogeny of the central nervous and immune systems.


Room temperature oxidation of Cu(3)Ge films grown on Si and Si(1-x)Ge(x) substrates.
Room temperature oxidation of Cu3Ge films grown on Si, Si(0.85)Ge(0.15) and Si(0.52)Ge(0.48) substrates, respectively, at a temperature of 200-300 degrees C was studied using transmission electron microscopy (TEM) in conjunction with energy dispersive spectrometry (EDS) and scanning electron microscopy (SEM). For Cu(3)Ge films grown at 200 degrees C and subsequently exposed in air for 1 week oxide protrusions and oxide networks appeared in the film surface and grain boundaries of Cu(3)Ge, respectively. At room temperature O from air and Si from the substrate, diffused along the grain boundaries of Cu(3)Ge to react with Cu(3)Ge grains, initiating the Cu(3)Si-catalyzed oxidation. Cu(3)Ge films are superior to Cu(3)(Si(1-x)Gex) films in retarding Cu(3)Si-catalyzed oxidation. Annealing at 300 degrees C allowed Si diffusion from the substrate into the Cu(3)Ge overlayer to form Cu(3)(Si(1-x)Gex), enhancing the Cu(3)Si-catalyzed oxidation rate. In the present study, Cu(3)Ge films grown on Si(0.52)Ge(0.48) at 200 degrees C show the best resistance to room temperature oxidation because higher Ge concentration in the substrate and lower temperature annealing can more effectively retard Si diffusion from the substrate into the Cu(3)Ge overlayer, and hence reduce the Cu(3)Si-catalyzed oxidation rate.


Thymoma-associated immunodeficiency: a syndrome characterized by severe alterations in NK, T and B-cells and progressive increase in naïve CD8+ T Cells.
Thymomas are rare tumours that sustain T-lymphopoiesis and trigger a variety of autoimmune diseases and immunodeficiencies, including a fatal hypogammaglobulinemia, namely Goods Syndrome (GS). Due to its rarity, GS has been poorly investigated and immunological features, as well as pathogenetic mechanisms underlying this syndrome, are unclear. We studied 30 thymoma patients by performing an immunological assessment, including immunophenotype and analysis of T cell repertoire (TCR). Development of GS was characterized by a progressive decrease in B, CD4 T and NK lymphocytes. These alterations paired with accumulation of CD8+CD45RA+ T cells that showed a polyclonal repertoire without expansions of specific clonotypes. GS is defined as hypogammaglobulinemia with thymoma. Here, we show for the first time that this syndrome is characterized by a severe loss of CD4+, NK and B cells. Furthermore, the accumulation of CD8+CD45RA+ T lymphocytes parallels these changes; this accumulation may have a role in determining the disease and can be used to monitor clinical stages of immunodeficiency in thymoma.


Nonintubated Spontaneous Respiration Anesthesia for Tracheal Glomus Tumor.
Previous tracheal surgeries were performed under tracheal and cross-field intubation. However, the intubation would lead to bleeding if the tumors were large or hemorrhagic. Moreover, the tracheal intubation might interfere the surgical vision and anastomosis during the reconstruction process. Therefore, we performed a tracheal tumor resection and reconstruction via nonintubated spontaneous anesthesia. We describe the feasibility and safety of tracheal surgeries via such anesthesia.


Validation of the Hospital Frailty Risk Score in older adults hospitalized with community-acquired pneumonia.
Frailty results from age-associated declines in physiological reserve and function and is prevalent in older people. Our aim is to examine the association of the Hospital Frailty Risk Score (HFRS) with adverse events in older patients hospitalized with community-acquired pneumonia (CAP) and hypothesise that frailty is a comparable predictor of outcomes in CAP versus traditional severity indices such as CURB-65. Retrospective review of electronic medical records in patients ≥65 years with CAP admitted to a tertiary hospital from 1 January to 30 April 2021. Patients were identified using ICD codes for CAP and categorized as high risk (>15), intermediate risk (5-15) and low risk (<5) of frailty using the HFRS. Of 429 patients with CAP, 53.8% male, mean age of 82.9 years, older patients (85 vs. 79.7 years, P < 0.001) were at higher risk of frailty. Using the HFRS, 47.6% were deemed at high risk, 35.9% at intermediate risk, and 16.6% at low risk of frailty. Multivariate logistic regression shows that HFRS was more strongly associated (≥7 days, OR 1.042, CI 1.017-1.069) than CURB-65 (OR 0.995, CI 0.810-1.222) with long hospital length of stay (LOS), while CURB-65 (Confusion, Urea >7mmol/L, Respiratory rate >30, Blood pressure, age => 65 years old) was more strongly associated with mortality at 30, 90 and 365 days, compared with the HFRS. Comparing the values for the area under the receiver operator characteristic curve, the HFRS was found to be a better predictor of long LOS, while CURB-65 remains a better predictor of mortality. Patients with high risk of frailty have higher healthcare utilization and HFRS is a better predictor of long LOS than CURB-65 but CURB-65 was a better predictor of mortality. Geriatr Gerontol Int 2023; ••: ••-••.


Two new motile phototrophic consortia: "Chlorochromatium lunatum" and "Pelochromatium selenoides"
Two new phototrophic consortia, "Chlorochromatium lunatum" and "Pelochromatium selenoides", were observed and collected in the hypolimnion of several dimictic lakes in Wisconsin and Michigan (USA). The two consortia had the same morphology but different pigment composition. The cells of the photosynthetic components of the consortia were half-moon-shaped. This morphology was used to differentiate them from the previously described motile phototrophic consortia "Chlorochromatium aggregatum" and "Pelochromatium roseum". These phototrophic cells did not resemble any described unicellular green sulfur bacteria. The predominant pigments detected were bacteriochlorophyll d and chlorobactene for the green-colored "Clc. lunatum", and bacteriochlorophyll e and isorenieratene for the brown-colored "Plc. selenoides". Their pigment compositions and the presence of chlorosomes attached to the inner face of the cytoplasmic membrane in both kinds of photosynthetic cells confirmed this new half-moon-shaped morphotype as a green sulfur bacterium. Both consortia were found thriving in lakes with low concentrations of sulfide (< 60 &mgr;M), below the layers of "Clc. aggregatum" and "Plc. roseum". The green consortia were observed in lakes where the oxic-anoxic interface was located at shallow depths (2-7 m), while the brown consortia were found at greater depths (8-16 m). The two newly described consortia were never detected together at the same depth in any lake.


Self-Powered UV-Near Infrared Photodetector Based on Reduced Graphene Oxide/n-Si Vertical Heterojunction.
A novel self-powered photodetector based on reduced graphene oxide (rGO)/n-Si p-n vertical heterojunction with high sensitivity and fast response time is presented. The photodetector contains a p-n vertical heterojunction between a drop-casted rGO thin film and n-Si. Contacts between the semiconductor layer (rGO, n-Si) and source-drain Ti/Au electrodes allow efficient transfer of photogenerated charge carriers. The self-powered UV-near infrared photodetector shows high sensitivity toward a spectrum of light from 365 to 1200 nm. Under the 600 nm illumination (0.81 mW cm-2 ), the device has a photoresponsivity of 1.52 A W-1 , with fast response and recover time (2 ms and 3.7 ms), and the ON/OFF ratios exceed 104 when the power density reaches ≈2.5 mW cm-2 . The high photoresponse primarily arises from the built-in electric field formed at the interface of n-Si and rGO film. The effect of rGO thickness, rGO reduction level, and layout of rGO/n-Si effective contact area on device performance are also systematically investigated.


The profile of patients with chronic kidney disease who regularly present at an Australian general practice.
Chronic kidney disease (CKD) is a common, serious and mostly asymptomatic condition that places considerable burden on the Australian healthcare system. Yet there is limited information on the patients with CKD who present to Australian primary care services, which represent the gateway to specialized care. Data pertaining to 31,897 patients who presented to a general practice in Western Australia, from 1 January 2013 to 30 June 2014 (inclusive), were extracted for review. Data included attendance records, comorbidities, diagnoses, and demographic details. Binary logistic regression was used to compare patients diagnosed with CKD by the consulting general practitioner with those without this diagnosis. Of the 8629 patients who regularly attended the practice, 184 (2%) were diagnosed with CKD (mean age: 77.7 years; male: 57.1%). The stage of CKD was recorded in only 8.4% of cases. Patients with CKD averaged 11 more consultations in the past 18 months (mean difference 10.8, 95% CI [9.3, 12.3], p < .001). They were also more likely to: be male; be ex-smokers; be widowed; and to have a carer. Their most common comorbidities included acute infections, cerebrovascular or ischemic heart disease, osteopenia or osteoporosis, and cancer; 8.7% had died within the previous year. Despite the prevalence of CKD, only one in five cases were recorded within this large practice. This reveals lost opportunities to monitor and manage patients with this chronic and common disease. Although this represents an important finding, this study is limited by the reliance on practice records, some of which were incomplete. Nevertheless, this study reveals two key findings. First, this disease is under-diagnosed and/or under-recorded. Second, patients with CKD have other, potentially unrelated, problems that may warrant attention.


An approach to excision of congenital giant pigmented nevi in infancy and early childhood.
This paper presents a timely coordinated approach to complete excision of congenital giant pigmented nevi in infancy and early childhood based on a review of 78 patients with giant pigmented nevi of the head and neck, trunk, and/or extremity. Giant pigmented nevi in those selected for review measured from a minimum of 2 percent up to 45 percent total body surface (TBS). Giant nevi of the scalp were treated most effectively using tissue expansion, beginning as early as 3 months of age. Expanded forehead and neck flaps in combination with expanded full-thickness skin grafts were used in early excision of giant pigmented nevi of the face. Giant nevi of the trunk were treated using a combination of abdominoplasty technique, tissue expansion, and split-thickness skin graft, with early "large segment" excision and grafting being the most effective treatment of giant nevi covering the posterior trunk. Giant nevi of the extremities were treated most effectively with excision and graft. Expanded full-thickness skin grafts gave excellent coverage on the hands and feet.


Risk for falls among community-dwelling older people: systematic literature review.
To identify the risk factors for falls of the community-dwelling elderly in order to update the Taxonomy II of NANDA International. A systematic literature review based on research using the following platforms: EBSCOHost®, CINAHL and MEDLINE, from December 2010 to December 2014. The descriptors used were (Fall* OR Accidental Fall) AND (Community Dwelling OR Community Health Services OR Primary health care) AND (Risk OR Risk Assessment OR Fall Risk Factors) AND (Fall* OR Accidental Fall) AND (Community Dwelling OR older) AND Nurs* AND Fall Risk Factors. The sample comprised 62 studies and 50 risk factors have been identified. Of these risk factors, only 38 are already listed in the classification. Two new categories of risk factors are proposed: psychological and socio-economical. New fall risk factors for the community-dwelling elderly have been identified, which can contribute to the updating of this nursing diagnosis of the Taxonomy II of NANDA International.


Facial Nerve Palsy Associated With Orthognathic Surgery.
The authors report a 25-year-old female who presented facial palsy after undergoing bimaxillary orthognathic surgery for retrognathism correction. Orthognathic surgery is a procedure used to treat dentofacial deformities which aims to achieve an adequate relationship between dental archs, improving function (such as chewing, breathing, and speaking) and facial aesthetics. Even though there are some complications that can occur during the intraoperative and postoperative periods like bleeding, tooth, soft-tissue damage, nerve damage, bad split, infection, and nonunion, facial nerve injuries are considered rare complications after this kind of surgical procedure. Despite being uncommon, rarely described, transient, and spontaneously resolved in almost all patients, facial nerve palsy is one of the most serious complications because it directly affects patient's quality of life and social interaction.


[Primary and secondary prevention of coronary heart disease: what can we afford?].
In secondary prevention, statins are cost-effective and even more cost-effective than other lipd lowering drugs. Statins are especially favorable in patients with previous myocardial infarction compared to those with angina pectoris. For secondary prevention of coronary heart disease, statins should be administered generously. In primary prevention, statins are effective but not cost-efficient. Unfavorable results have to be expected especially in premenopausal women, younger patients, and in those with a low risk factor profile. For population based primary prevention, only dietary measures can be advocated; however, apart from a serious lack of compliance their efficiency has not yet been proven. Preventive measures have their own prize; in general they are considered not to prevent coronary heart disease but retard it. Therefore, such therapeutic interventions can be assumed not to reduce but rather to increase the "direct" medical costs. Furthermore, successful prevention of coronary heart disease leads, due to life-prolongation, to an increase in people out of work and in disabled patients due to age and/or disease. Therefore, an increase especially of the "indirect" costs for unemployment, pension, nursing homes, etc. must be expected.


Gastric Bypass after multiple restrictive procedures: Roux-en-Y or One Anastomosis? A retrospective multicentric study.
When restrictive surgery fails, conversion to more malabsorptive techniques is frequently proposed. The aim of this study is to evaluate the weight loss figures between Roux-en-Y Gastric Bypass (RYGB) and One Anastomosis Gastric Bypass (OAGB) in patients who have already undergone Multiple Restrictive Procedures (MRP). All patients who underwent conversion of Laparoscopic Sleeve Gastrectomy (LSG) to RYGB or OAGB between 2010 and 2019 were retrospectively analyzed. Only patients who had conversion for Weight Regain (WR) or Insufficient Weight Loss (IWL) after both Laparoscopic Gastric Banding (LGB) and LSG entered the study population. Finally, 44 patients underwent conversion to RYGB, and 24 patients to OAGB. Concerning Excess Weight Loss (%EWL) at 3, 6, 12, 24 postoperative months, the results for RYGB were 33.7%, 47.95%, 61.8%, 61.8%, while for OAGB were 38.3%, 51.9%, 63.75%, 79.45%. A significant difference was recorded in favor of OAGB at 3 (p=0.03) and 24 (p=0.046) postoperative months. % EWL at 24 months in the case of IWL was 57.8% for RYGB, while for OAGB was 72.7% (p=0.047). No significant difference was found considering patients with WR (80.9% and 80.5%; p= 0.999). Patients with better results at 24 months after surgery had a significantly longer time between sleeve and bypass than those with a lower % EWL. The results of the present study seem to show that both techniques give good results at 24 months in patients who have undergone MRP. However, OAGB shows overall better results, particularly in patients with IWL.


The Potential Role of Gut Microbiota in the Pathogenesis of Type 2 Diabetes Mellitus via Epigenetics and Inflammasome.
The gut microbiota that comprises over 100 trillion microorganisms with a weight of about 1-2 kg is regarded as one of the most crucial players in the regulation of the metabolic health of host organisms. In recent years, the incidence of type 2 diabetes mellitus (T2DM), characterized by high levels of sugar in the blood, has been exponentially increasing due to obesity and other lifestyle risk factors. It was shown that dysbiosis, change in the overall composition, and diversity of gut microflora can result in T2DM. Conversely, the microbial composition can also influence the epigenetics of the host organism (DNA methylation as well as histone modifications), which might have a potential effect on the metabolic health of the individual. Another mechanism of gut microbiota in the development of T2DM is through the involvement of nucleotide-binding oligomerization domain, Leucine-rich Repeat, and Pyrin domain containing 3 (NLRP3) inflammasome, a part of the innate immune system. NLRP3 inflammasome produces inflammatory cytokines, promoting the secretion of microbial antigens in the intestinal epithelium. Therefore, it is important to understand the possible connecting link between gut microbiota and T2DM that might help in the modulation of gut microflora to better understand the disease. In this review, the role of gut microbiota in the pathogenesis of T2DM will be discussed.


Pharmacodynamics of the new fluoroquinolone gatifloxacin in murine thigh and lung infection models.
Gatifloxacin is a new 8-methoxy fluoroquinolone with enhanced activity against gram-positive cocci. We used the neutropenic murine thigh infection model to characterize the time course of antimicrobial activity of gatifloxacin and determine which pharmacokinetic (PK)-pharmacodynamic (PD) parameter best correlated with efficacy. The thighs of mice were infected with 10(6.5) to 10(7.4) CFU of strains of Staphylococcus aureus, Streptococcus pneumoniae, or Escherichia coli, and the mice were then treated for 24 h with 0.29 to 600 mg of gatifloxacin per kg of body weight per day, with the dose fractionated for dosing every 3, 6, 12, and 24 h. Levels in serum were measured by microbiologic assay. In vivo postantibiotic effects (PAEs) were calculated from serial values of the log(10) numbers of CFU per thigh 2 to 4 h after the administration of doses of 8 and 32 mg/kg. Nonlinear regression analysis was used to determine which PK-PD parameter best correlated with the numbers of CFU per thigh at 24 h. Pharmacokinetic studies revealed peak/dose values of 0.23 to 0.32, area under the concentration-time curve (AUC)/dose values of 0.47 to 0.62, and half-lives of 0.6 to 1.1 h. Gatifloxacin produced in vivo PAEs of 0.2 to 3.1 h for S. pneumoniae and 0.4 to 2.3 h for S. aureus. The 24-h AUC/MIC was the PK-PD parameter that best correlated with efficacy (R(2) = 90 to 94% for the three organisms, whereas R(2) = 70 to 81% for peak level/MIC and R(2) = 48 to 73% for the time that the concentration in serum was greater than the MIC). There was some reduced activity when dosing every 24 h was used due to the short half-life of gatifloxacin in mice. In subsequent studies we used the neutropenic and nonneutropenic murine thigh and lung infection models to determine if the magnitude of the AUC/MIC needed for the efficacy of gatifloxacin varied among pathogens (including resistant strains) and infection sites. The mice were infected with 10(6.5) to 10(7.4) CFU of four isolates of S. aureus (one methicillin resistant) per thigh, nine isolates of S. pneumoniae (two penicillin intermediate, four penicillin resistant, and two ciprofloxacin resistant) per thigh, four isolates of the family Enterobacteriaceae per thigh, a single isolate of Pseudomonas aeruginosa per thigh, and 10(8.3) CFU of Klebsiella pneumoniae per lung. The mice were then treated for 24 h with 0.29 to 600 mg of gatifloxacin per kg every 6 or 12 h. A sigmoid dose-response model was used to estimate the dose (in milligrams per kilogram per 24 h) required to achieve a net bacteriostatic effect over 24 h. MICs ranged from 0.015 to 8 microg/ml. The 24-h AUC/MICs for each static dose (1.7 to 592) varied from 16 to 72. Mean +/- standard deviation 24-h AUC/MICs for isolates of the family Enterobacteriaceae, S. pneumoniae, and S. aureus were 41 +/- 21, 52 +/- 20, and 36 +/- 9, respectively. Methicillin, penicillin, or ciprofloxacin resistance did not alter the magnitude of the AUC/MIC required for efficacy. The 24-h AUC/MICs required to achieve bacteriostatic effects against K. pneumoniae were quite similar in the thigh and lung (70 versus 56 in neutropenic mice and 32 versus 43 in nonneutropenic mice, respectively). The magnitude of the 24-h AUC/MIC of gatifloxacin required for efficacy against multiple pathogens varied only fourfold and was not significantly altered by drug resistance or site of infection.


Tricuspid annular plane systolic excursion is a predictor of mortality for septic shock.
Cardiac dysfunction is a common sequela in patients with sepsis and multi-organ dysfunction. Echocardiography is commonly used in the investigation of circulatory failure. We aimed to evaluate the prognostic value of echocardiographic parameters in patients with septic shock. This study was a retrospective trial. We included patients who were admitted to intensive care unit (ICU) with septic shock. The patients' echocardiograms, clinical data and outcomes were obtained from their medical records. Associations between echocardiogram variables and mortality were assessed using logistic regression, controlled for age, sex, body mass index and the interval between the ICU admission and echocardiogram. The utility of statistically significant echocardiogram variables to predict mortality were assessed using receiver operating characteristic (ROC) curves. The outcomes presented that tricuspid annular plane systolic excursion (TAPSE) was statistically significantly associated with both ICU (P = 0.02) and 90-day (P = 0.001) mortality. From the ROC curves, TAPSE emerged a significant and moderate predictor for 90-day (area under curve (AUC) = 0.69, 95% CI = 0.565-0.814) and in-ICU mortality (AUC = 0.762, 95% CI = 0.652-0.871). The optimal cut-off for TAPSE was 2.1 cm for both 90-day mortality (sensitivity of 80% and specificity and 58%) and in-ICU mortality (sensitivity of 69% and specificity of 77%). TAPSE was associated with increased mortality in those with sepsis and suspicion of cardiac dysfunction. This is a hypothesis generating article that an association may be present and requires significant more work with expansion to the entire population base.


Formation of hemoglobin and albumin adducts of benzene oxide in mouse, rat, and human blood.
Little is known about the formation and disposition of benzene oxide (BO), the initial metabolite arising from oxidation of benzene by cytochrome P450. In this study, reactions of BO with hemoglobin (Hb) and albumin (Alb) were investigated in blood from B6C3F1 mice, F344 rats, and humans in vitro. The estimated half-lives of BO in blood were 6.6 min (mice), 7.9 min (rats), and 7.2 min (humans). The following second-order rate constants were estimated for reactions between BO and cysteinyl residues of Hb and Alb [in units of L (g of Hb- or Alb-h)-1]: mouse Hb = 1.16 x 10(-)4, rat Hb = 15.4 x 10(-)4, human Hb = 0.177 x 10(-)4, mouse Alb = 2.68 x 10(-)4, rat Alb = 4.96 x 10(-)4, and human Alb = 5.19 x 10(-)4. These rate constants were used with BO-adduct measurements to assess the systemic doses of BO arising from benzene in vivo in published animal and human studies. Among rats receiving a single gavage dose of 400 mg of benzene/kg of body weight, the BO dose of 2.62 x 10(3) nM BO-h, predicted from Alb adducts, was quite similar to the reported AUC0-infinity = 1.09 x 10(3) nM BO-h of BO in blood. Interestingly, assays of Hb adducts in the same rats predicted a much higher dose of 14.7 x 10(3) nM BO-h, suggesting possible in situ generation of adducts within the erythrocyte. Doses of BO predicted from Alb adducts were similar in workers exposed to benzene [13.3 nM BO-h (mg of benzene/kg of body weight)-1] and in rats following a single gavage dose of benzene [8. 42 nM BO-h (mg of benzene/kg of body weight)-1]. Additional experiments indicated that crude isolates of Hb and Alb had significantly higher levels of BO adducts than dialyzed proteins, suggesting that conjugates of low-molecular-weight species were abundant in these isolates.


Responsible handling of ethics in data publication.
A global working group has developed recommendations for the responsible handling of the growing range of ethics cases related to data publication, but further community work is needed toward a responsible and cohesive data publishing ecosystem.


The successful introduction of a programme to reduce the use of i.v. ciprofloxacin in hospital.
The effectiveness of a programme to reduce the use of i.v. ciprofloxacin was assessed. i.v. ciprofloxacin was removed from ward stock and discussion occurred regarding appropriate use of the drug. Six months later, a factsheet containing recommendations was distributed to all medical staff and a requirement for justification before prescription was introduced. The programme reduced expenditure on i.v. ciprofloxacin to 34% of original levels. Savings of > 36,000 pounds sterling were made for two consecutive years. A sustained reduction in the use of i.v. ciprofloxacin was obtained by a combination of education and restriction.


Chemistry of polycarbon species: from clusters to molecular devices.
Polycarbon species with pi-conjugated systems interact with attached metal fragments to exhibit a variety of intriguing structural features and chemical properties. In this Perspective, following an introductory account of polycarbon cluster compounds and the unique chemical transformations on them which cannot easily be realized by mononuclear species, the properties of polynuclear complexes connected by pi-conjugated carbon-rich bridging ligands will be discussed with emphasis on those applicable to molecular electronics, e.g. wire-like behavior (molecular wires), higher dimensional systems (branch circuits), and switching functions.


Articulatory changes in muscle tension dysphonia: evidence of vowel space expansion following manual circumlaryngeal therapy.
In a preliminary study, we documented significant changes in formant transitions associated with successful manual circumlaryngeal treatment (MCT) of muscle tension dysphonia (MTD), suggesting improvement in speech articulation. The present study explores further the effects of MTD on vowel articulation by means of additional vowel acoustic measures. Pre- and post-treatment audio recordings of 111 women with MTD were analyzed acoustically using two measures: vowel space area (VSA) and vowel articulation index (VAI), constructed using the first (F1) and second (F2) formants of 4 point vowels/ a, i, ae, u/, extracted from eight words within a standard reading passage. Pairwise t-tests revealed significant increases in both VSA and VAI, confirming that successful treatment of MTD is associated with vowel space expansion. Although MTD is considered a voice disorder, its treatment with MCT appears to positively affect vocal tract dynamics. While the precise mechanism underlying vowel space expansion remains unknown, improvements may be related to lowering of the larynx, expanding oropharyngeal space, and improving articulatory movements. The reader will be able to: (1) describe possible articulatory changes associated with successful treatment of muscle tension dysphonia; (2) describe two acoustic methods to assess vowel centralization and decentralization, and; (3) understand the basis for viewing muscle tension dysphonia as a disorder not solely confined to the larynx.


Assessment of female prevalence of overactive bladder (OAB) in Barcelona using a self-administered screening questionnaire: the Cuestionario de Autoevaluación del Control de la Vejiga (CACV).
Overactive bladder (OAB) syndrome is common urological condition, usually underdiagnosed and difficult to identify. The screening of lower urinary tract symptoms (LUTS) through patient self-administered questionnaires can be useful not only for timely identification of these patients but to implement early interventions for symptoms and their implication in a patients' quality of life (QOL). Our objective was to assess the prevalence of OAB symptoms in patients attending general gynecology units in Barcelona, Spain, through a self-administered screening questionnaire. A cross-sectional, multicenter, observational, epidemiological study was carried out at general gynecology units of ten primary health centers in Barcelona, Spain. The study was conducted during a patient's single visit through self-administered forms. Patients recorded sociodemographic data, medical history and comorbidities, and scored the presence and bother related to specific urological symptoms using the Cuestionario de Autoevaluación del Control de la Vejiga (CACV), the validated Spanish version of the Bladder Control Self-Assessment Questionnaire (B-SAQ). A score ≥6 on the symptoms scale of the CACV was taken as an indicator of suspected OAB. One thousand and four women aged between 18 and 82 participated in the study. The overall prevalence of OAB was 11.8 %. A patient being >50 years was significantly associated with suspected OAB in comparison with the younger group [odds ratio (OR) 3.1 (2.1-4.7); p < 0,001]. Overactive bladder showed significant association with factors other than age, menopause, and previous urogynecological history, such as high body mass index (BMI) and parity. The estimated prevalence of suspected OAB in patients attending general gynecological services in Barcelona is 11.8 %. Overweight or obese patients and those with three or more children were found to be at elevated risk for developing OAB.


A case of endocarditis mimicking Crimean-Congo haemorrhagic fever.
Infective endocarditis (IE) is life-threatening condition with a highly variable clinical presentation. We report a case of acute IE with delayed diagnosis which resulted due to an initial misdiagnosis of Crimean Congo Hemorrhagic Fever (CCHF) in an endemic area. A case was due to Staphylococcus aureus and requiring valve replacement. They serve to emphasize the importance of careful history taking, physical examination and a broad range of different diagnostic techniques in the context of suspected viral hemorrhagic fever.


Image registration assessment in radiotherapy image guidance based on control chart monitoring.
Image guidance with cone beam computed tomography in radiotherapy can guarantee the precision and accuracy of patient positioning prior to treatment delivery. During the image guidance process, operators need to take great effort to evaluate the image guidance quality before correcting a patient's position. This work proposes an image registration assessment method based on control chart monitoring to reduce the effort taken by the operator. According to the control chart plotted by daily registration scores of each patient, the proposed method can quickly detect both alignment errors and image quality inconsistency. Therefore, the proposed method can provide a clear guideline for the operators to identify unacceptable image quality and unacceptable image registration with minimal effort. Experimental results demonstrate that by using control charts from a clinical database of 10 patients undergoing prostate radiotherapy, the proposed method can quickly identify out-of-control signals and find special cause of out-of-control registration events.


Spatio-Temporal Spread of Grapevine Leafroll Disease in Washington State Vineyards.
The spread of grapevine leafroll disease (GLD) to vineyards planted with certified planting stock is of significant concern to grape growers. In this study, the spatial and temporal spread of GLD was examined in three vineyard blocks planted with virus-tested wine grape (Vitis vinifera) cultivars adjacent to vineyard blocks heavily infected with GLD in two geographic locations in eastern Washington State. During each season, the position of vines showing GLD symptoms was recorded in a matrix representing the planting lattice. Symptomatic vines were positive only for Grapevine leafroll-associated virus 3 (GLRaV-3), the most common virus species consistently associated with GLD in Washington vineyards. The results from multiple seasons showed a gradual increase in disease incidence over time in all three blocks. Spatial and temporal mapping of GLD indicated a disease gradient in which the highest percentage of symptomatic vines was in rows proximal to infected old blocks. Spatial autocorrelation analysis using Moran's I values suggested random patterns of symptomatic vines in the three blocks during initial years, indicating primary spread of the virus not related to infected vines within the block. Clustering at the scale of neighboring vines during subsequent years suggested secondary spread within the block. Results of quadrat-based spatial analyses of GLD incidence were compared with previously reported data obtained from California and elsewhere for an improved understanding of the dynamics of GLD spread to facilitate area-wide disease management strategies.


[Community health technical personnel].
In this article the author describes his experience in training community health officers at the Community Health School of the State of Mexico. She presents her views on the training of this type of personnel to work in the rural areas of developing countries; described the fundamental characteristics of their training and the methods used; and indicates the difficulties encountered by the first graduates of the above-mentioned School when they took up their duties.


An acute form of tyrosinemia type I with multiple intrahepatic mass lesions.
The acute form of tyrosinemia type I usually causes severe hepatocellular dysfunction. We report a 4-month-old infant with hepatosplenomegaly, ascites, and multiple intrahepatic mass lesions mimicking hepatoma. A marked increase of serum alpha-fetoprotein (97.6 micrograms/ml) and multiple small low-density lesions in the liver demonstrated by computed tomography suggested the presence of hepatoma. The liver specimens obtained at laparatomy showed mixed nodular cirrhosis with fatty metamorphosis. Serum levels of tyrosine (6.6 mg/100 ml) and methionine (5.9 mg/100 ml) were increased. Urinary organic acid analyses disclosed increased excretions of succinylacetone (1,330 mg/g creatinine) and delta-amino-levulinic acid (113.6 mg/g creatinine). Histological abnormalities and biochemical evidences led to the correct diagnosis. This case emphasizes the need for complete investigations of puzzling cases and warns against undue reliance on noninvasive imaging techniques.


Learning physics of living systems from Dictyostelium.
Unlike a new generation of scientists that are being trained directly to work on the physics of living systems, most of us more senior members of the community had to find our way from other research areas. We all have our own stories as to how we made this transition. Here, I describe how a chance encounter with the eukaryotic microorganism Dictyostelium discoideum led to a decades-long research project and taught me valuable lessons about how physics and biology can be mutually supportive disciplines.


Does Mindfulness Correlate With Physical Function and Pain Intensity in Patients With Upper Extremity Illness?
Mindfulness skills training interventions seem efficacious in increasing physical function and decreasing pain intensity in patients with chronic pain. The relationship of mindfulness and upper extremity complaints in patients presenting to orthopedic surgical practices is not known. The aim of this study was to assess if mindfulness has a relationship to physical function and pain intensity in patients with upper extremity illness. In this cross-sectional study, a total of 126 patients with a nontraumatic upper extremity condition were asked to fill out questionnaires assessing the 5 facets of mindfulness, pain intensity, and upper extremity physical function, along with clinical and demographic variables prior to their visit with the surgeon. Nonreactivity to inner experiences was the only facet of mindfulness that was correlated with upper extremity physical function and pain intensity. The overall mindfulness score was correlated with pain intensity only. In multivariable analyses, mindfulness was not associated with either physical function or with pain intensity. Pain interference was the most important predictor of both pain intensity and physical function. Greater overall mindfulness was associated with lower pain intensity, and greater ability to be nonreactive to inner experiences was associated with both pain intensity and upper extremity physical function in bivariate but not multivariable analyses. Pain interference was the most important predictor of both pain intensity and upper extremity physical function. Psychosocial interventions focused on improving physical function and decreasing pain intensity in this population should focus primarily on reducing pain interference, and secondarily on teaching patients mindfulness skills.


Pediatric Cellulitis: A Red-Hot Concern.
Cellulitis and other skin and soft tissue infections are a common reason for children to seek care, both in the primary care setting and the emergency department. Cellulitis is a common skin and soft-tissue infection that is usually caused by streptococci bacteria or, less commonly, Staphylococcus aureus. Most children recover quickly from cellulitis, but a small subset will require hospitalization. Practitioners need to be skilled in the diagnosis and treatment of cellulitis, including recognition of the need for inpatient treatment. However, diagnosis of cellulitis, and exclusion of complicated or other more serious infections, can be challenging. Management of these infections has also been highly variable, resulting in some difficulty identifying the ideal treatment regimen. The goal is to use the antibiotic with the narrowest spectrum for the shortest duration necessary to provide clinical improvement. Research to identify the best treatment for pediatric cellulitis will be important moving forward. [Pediatr Ann. 2017;46(7):e265-e269.].


Ten years of fertility treatment experience and reproductive options in transgender men.
Up to 2018, the Belgian law stated that transgender people who wanted to change their legal sex had to undergo physical gender affirming treatment. This included gonadectomy to a medically possible and justified extent, which entailed that they had to accept the fact that they could no longer reproduce. However, research has shown that many transgender people desire to have children. (1) to describe a cohort of transgender men and their respective cisgender female partners, to share our experiences with their request for donor conception, and to evaluate their disclosure intentions to the child, (2) to explore how the couples approach current and future reproductive options. This mixed method study presents data from a retrospective analysis of patient records and from a qualitative interview study. The couples were selected from the group of transgender men who - together with their respective cisgender female partners - applied for sperm donation at Ghent University Hospital between 2002 and 2012. Forty-seven transgender men with a cisgender female partner requested treatment with anonymous donor sperm for a first child as a couple. Forty-one requests were accepted for treatment. We found that most couples requesting treatment intended to disclose the use of donor sperm to their future child (n = 34) while 24 couples were planning to inform the child about the parent's transgender identity. The six couples we interviewed saw donor conception as the preferred route to become parents. Adoption was seen as less obvious. The couples' attitudes toward stem cell-derived gametes reflected the significance of the genetic link with the child for both parents. Not all participants in our study were aware of their reproductive options. To be able to make a well-informed decision, transgender people should be counseled about all options at the time of transition.


Treatment of Severe Postburn Contracture of the Elbow via Distraction With External Circular Frame in Pediatric Patient.
Although external circular frame (ECF) has been widely used for the correction of knee and ankle deformities, few studies reported the use of ECF for the treatment of severe postburn elbow contracture and stiffness (SPECS). The purpose of this retrospective study was to investigate the effectiveness and safety of the distraction using ECF in treating SPECS. After institutional review board approval, we implemented a retrospective single-center case series study composed of consecutive patients treated for SPECS at Chinese PLA General Hospital between January 2010 and January 2018. After scar release and skin grafting, distraction with ECF was performed for 4 to 6 weeks, and the frame was retained for 2 more weeks before removal. Four weeks of splinting and at least 1 year of rehabilitation were recommended. Patient demographics, active and passive range of motion (ROM) of the elbow at different time points (preoperative, postdistraction, and final follow-up), and complications were collected from the electronic medical record. The primary outcome was the long-term improvement of the ROM. Other outcomes included complications and recurrence. The ECF was used to treat SPECS in 6 patients (3 males and 3 females, average age of 11.7 ± 2.6 years). Scar release and distraction with ECF significantly increased both active (from 3° preoperative to 38.7° postdistraction) and passive (from 3.5° preoperative to 48.3° postdistraction) ROM over an average distraction duration of 5.2 weeks. The long-term improvement of active and passive ROM was 38° ± 13.4° and 46° ± 14.7°, respectively, over a median follow-up of 4.1 years. Pin-tract infection occurred in 2 patients and were treated with local wound care and oral antibiotics. A tendon readhesion developed in 1 of the 6 patients because of noncompliance with splinting and physiotherapy, and was treated with revision surgery. The 3C strategy (i.e., contracture release, coverage of the defect with skin grafting, and correction of articular angle with gradual distraction using the ECF) is able to increase the ROM with minor complications. We recommend distraction with ECF as part of the treatment arsenal, particularly for severe contractures in which 1-stage correction is unfeasible because of considerable soft tissue shortening.


Immunological and immunohistochemical analysis of rheumatoid nodules.
An attempt was made to examine the pathophysiology of the rheumatoid nodule. Significant amounts of interleukin 1-like activity and prostaglandin E2 were detected in the supernatants from in vitro organ cultures of rheumatoid nodule tissue. When fresh (but not old) rheumatoid nodules were minced and cultured in vitro prominent outgrowths of cells were observed. These cells expressed both HLA-DR and CD14 antigens but lacked conventional differentiation antigens for T cells and B cells, suggesting that they are of monocyte-macrophage origin. These data suggest that interleukin 1 and prostaglandin E2 may be deeply involved in the formation of rheumatoid nodules.


Langerhans cell histiocytosis presenting as bilateral eosinophilic granulomata in the molar region of the mandible. A case report.
Eosinophilic granuloma represents one of a triad of lesions encompassing a disease under the generic name, histiocytosis X or Langerhans cell histiocytosis. Localised eosinophilic granuloma, multifocal eosinophilic granuloma, Hand-Schüller-Christian disease, and the most malignant form of histiocytosis, Letterer-Siwe disease, can all present as destructive bony lesions of the jaws. The present case was a 30-year-old man who presented with almost total destruction of the periodontal support to the left and right mandibular, 1st and 2nd molars. Whereas the radiographic features were typical of eosinophilic granuloma, the clinical appearance and mirror image presentation were unusual.


CE: The obesity epidemic, part 2: nursing assessment and intervention.
Although there are many gaps in our understanding of the mechanisms underlying obesity, several nursing strategies have proven effective in combating this public health crisis. This article, the second in a two-part series, presents a theoretical framework to guide nursing assessment of affected patients and their families, thereby informing intervention. The authors discuss the effects of stigma and bias on the treatment of obesity; how to conduct a thorough assessment of an obese patient; the effectiveness of the most common lifestyle, pharmacologic, and surgical interventions for obesity; and issues to consider in the treatment of obese children. Part 1, which appeared in last month's issue, provided background on the epidemic; defined terms used in obesity treatment; and described pathophysiologic, psychological, and social factors that influence weight control.


Primary epithelioid hemangioendothelioma of the clivus.
We describe the clinical, radiologic, and pathologic features of a primary intracranial hemangioendothelioma arising in the clivus in a 38-year-old female, emphasizing the importance of including this rare entity in the differential diagnosis of tumors arising at the base of the skull. To our knowledge, this is the first reported case of a clival hemangioendothelioma. Aside from its unusual location, this case is also notable for its apparent rapid growth and mixed epithelioid-spindle cell morphology. Appropriate neuroimaging studies may offer crucial information, ensuring that this uncommon entity is included in the differential diagnosis of a clival mass.


Are intrauterine growth restriction and preterm birth associated with dental caries?
To assess the association between two intrauterine growth restriction (IUGR) surrogates - IUGR [small for gestational age birth (SGA) and fetal growth restriction (FGR)] and preterm birth with dental caries. Data from the Third National Health and Nutritional Examination Survey (1988-1994) were used, including 2- to 5.9-year-old singletons (n = 3189). Dental caries was defined as presence of any teeth with dental caries (treated or untreated) and also as presence of at least two teeth with dental caries. Exposure variables were preterm birth (<37 gestational weeks), FGR, and SGA. Covariates included were poverty, race/ethnicity, age, sex, sucrose intake, environmental tobacco smoking, dental visits, education of head of household, breastfeeding, and use of baby bottle. Separate statistical analyses were conducted for IUGR and for preterm birth through the estimation of prevalence ratio (PR), taking complex sampling design into consideration and adjusting for confounders. Sensitivity analysis was conducted including and excluding 2-year-old children and also with the two definitions of dental caries. In general, the inclusion of 2-year-old children and the case definition of presence of any teeth with dental caries biased the results toward the null, but with no major changes in the results. In bivariate analysis, SGA and FGR birth were both negatively but not significantly associated with dental caries while a significant positive association was found for preterm birth. Sensitivity analysis showed that the PR for preterm in bivariate analysis varied from 1.65 (95% CI 1.14-2.40) to 1.84 (95% CI 1.19-2.83). After adjusting for confounders, the PR for preterm birth varied from 1.38 (95% CI 1.00-1.89) to 1.64 (95% CI 1.22-2.20). After adjustment, the PR for SGA varied from 0.79 (95% CI 0.56-101) to 0.66 (95% CI 0.33-0.96). For children from 3 to 5.9 years old, the adjusted PR for FGR using the category 'none' as reference were mild (PR 1.10; 95% CI 0.76-1.58), moderate (PR 0.66; 95% CI 0.26-167), and severe (PR 0.59; 95% CI 0.36-0.99). These values for FGR were very similar for the other models using other classifications of case definition or inclusion of 2-year-old children. Preterm birth was found to be positively associated with dental caries while there is an indication that SGA and FGR are negatively associated with dental caries. Although the negative association is counterintuitive, it is possible that increased antibiotic use and delayed tooth eruption may explain the negative association between IUGR and dental caries.


A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience.
To determine the clinical presentation and clinical and radiological outcome of early psoriatic arthritis (PsA) at 1 and 2 yr. Patients with PsA were assessed at the St. Vincent's University Hospital Early Synovitis Clinic. Standardized clinical and laboratory assessment was performed at presentation and 1- and 2-yr follow-up. Radiographs of the hands and feet were evaluated in chronological order by two trained observers using the Sharp method modified to include the distal interphalangeal (DIP) joints. A total of 129 (12.7%) of 1018 patients were diagnosed with PsA [mean age at onset of arthritis was 40.4 yr (range 11-76); mean duration of disease was 9.9 months (range 0.3-48); 52 oligoarticular, 77 polyarticular]. Means and standard deviations of indices of disease activity at presentation were: 10-cm visual analogue scale = 4.8 +/- 2.7, HAQ score = 0.71 +/- 0.64, ACR functional class III/IV = 41 (35%), Ritchie Articular Index = 5.6 +/- 6, swollen joint count = 6.9 +/- 8, erythrocyte sedimentation rate = 24 +/- 26.4 mm/h, C-reactive protein = 27.6 +/- 58.5 mg/l. At presentation, 49 (38%) patients had peripheral enthesopathy, 13 patients (10%) had inflammatory spine pain and 50 (39%) patients had DIP involvement. A total of 119 had psoriasis at the time of presentation [plaque psoriasis in 112 (94%), mean age of psoriasis onset was 29.8 +/- 16.2 yr, nail dystrophy present in 78 patients (67%)]. At 1 yr of follow-up, 119 (92%) patients were reassessed and 70 (59%) were taking a disease-modifying anti-rheumatic drug (DMARD). At 2 yr, 97 (75%) patients were reassessed and 54 (56%) were taking a DMARD. Despite considerable improvement in inflammation and function scores, only 31 (26%) patients were in remission at 1 yr with 20 (21%) in remission at 2 yr. There was a low rate of DMARD-free remission [14 (12%) at 1 yr and 11 (11%) at 2 yr]. Radiographs of hands and feet were obtained for 117 (91%) patients at presentation and 86 (67%) patients at a median follow-up of 24 months (range 11-56); 47% of patients had joint erosions in hands or feet at follow-up with a mean Sharp erosion score of 3 (0) +/- 5.2 (range 0-25) and a mean Sharp narrowing score of 3.2 (0) +/- 7.5 (range 0-48). This study confirms that PsA is a chronic, progressive disease in the majority of patients. Despite clinical improvement with current DMARD treatment, PsA results in radiological damage in up to 47% of patients at a median interval of 2 yr.


Characteristics and Correlates of Cigarette Smoking Status Among US Adults Receiving Federal Housing Assistance.
This study describes patterns of cigarette smoking (current, former, never) by sociodemographic, household, and chronic disease characteristics and correlates among US adults receiving housing assistance from the US Department of Housing and Urban Development (HUD) during 2007-2012. Estimates were generated from 4,771 adults by using National Health Interview Survey and HUD-linked data. Overall, 48.4% of HUD-assisted adults were never smokers, 33.0% were current smokers, and 18.6% were former smokers; smoking status varied by sex, age, race/ethnicity, whether children were living in the household, and chronic disease status. These estimates could inform tobacco control interventions to improve the health and well-being of HUD-assisted residents.


Universal magnetic structure of the half-magnetization phase in Cr-based spinels.
Using an elastic neutron scattering technique under a pulsed magnetic field up to 30 T, we determined the magnetic structure in the half-magnetization plateau phase in the spinel CdCr2O4. The magnetic structure has a cubic P4{3}32 symmetry, which is the same as that observed in HgCr2O4. This suggests that despite their different zero-field ground states a universal field-induced spin-lattice coupling mechanism is at work in the Cr-based spinels.


Surveillance for primary and secondary syphilis--United States, 1991.
From 1986 through 1990, an epidemic of syphilis occurred throughout the United States. In 1991, the number of reported cases of primary and secondary (P&S) syphilis in the United States declined for the first time since 1985. To examine how this decline reflected sex-specific, race/ethnicity-specific, and regional patterns of syphilis morbidity, we analyzed data for syphilis cases reported to CDC from 1984 through 1991. Summary data for cases of syphilis reported to state health departments were sent quarterly and annually to CDC. The quarterly data from each state included total number of syphilis cases by sex, stage of disease (primary, secondary, early latent, and late latent), and source of report (public or private). The annual data from each state included total number of P&S syphilis cases by sex, racial/ethnic group (white, not of Hispanic origin; black, not of Hispanic origin; Hispanic; Asian/Pacific Islander; or American Indian/Alaskan Native), 5-year age group, and source of report. The decline in both the number and rate of reported syphilis cases in 1991 occurred in every racial group in the United States and in both sexes. This decline also occurred in every region of the United States except the Midwest, where the total P&S syphilis rate increased 37.3% from 1990 through 1991. Despite the increase in syphilis rates in the Midwest, the highest rates of P&S syphilis in 1991 were reported from the South. The reasons for the decline in syphilis are unclear. No data exist to conclusively identify which STD control program activities affected the level of syphilis morbidity or to what extent those activities may have contributed to the decline. Changes in drug use and limited immunity to Treponema pallidum may have accounted for some of the decrease in syphilis incidence. Higher levels of poverty in the South and poor access to health-care services associated with poverty probably contributed to continued high levels of disease transmission in the South. Better evaluation of STD control program activities will be necessary to help determine the most effective strategies for preventing and controlling syphilis in different high-risk populations.


Epidemiology of HIV/AIDS in the East Azerbaijan Province, Northwest of Iran.
This study was performed in response to the rapid propagation of HIV/AIDS across Iran and its status in this region. Accordingly, an evidence-based program is required to combat this disease. The present study estimated the prevalence of HIV/AIDS in East Azerbaijan (population: 3,724,000). We created a database of all positive cases from 1987 to 2012. We also analyzed and described the epidemiological status of HIV/AIDS during a 25-year period by using SPSS. In East Azerbaijan, 371 HIV/AIDS cases have been reported, i.e. 1 case per 10,000 population. The vast majority of reported cases (91%, n =338) were men, whereas only 9% (n = 33) were women. The mean age of patients was 30.8 ± 12.3 years. Unsafe drug injection (59%, n = 219) and sexual interaction (13%, n = 48) were the two major modes of HIV transmission. In addition, 7% (n = 25) of patients have been diagnosed with HIV, hepatitis B Virus, and hepatitis C virus simultaneously. Moreover, 60% (n = 205) of men were infected via drug injection, while 82% (n = 27) of women were infected via unprotected sexual interaction (P < 0.001). The results indicate a rapid increase in the number of HIV/AIDS cases in East Azerbaijan, necessitating immediate attention and strategies to combat the rapid spread of the disease. Development of provincial and national HIV/AIDS strategies demands more accurate and comprehensive HIV/AIDS surveillance.


Climate change, fire return intervals and the growing risk of permanent forest loss in boreal Eurasia.
Climate change has driven an increase in the frequency and severity of fires in Eurasian boreal forests. A growing number of field studies have linked the change in fire regime to post-fire recruitment failure and permanent forest loss. In this study we used four burned area and two forest loss datasets to calculate the landscape-scale fire return interval (FRI) and associated risk of permanent forest loss. We then used machine learning to predict how the FRI will change under a high emissions scenario (SSP3-7.0) by the end of the century. We found that there are currently 133,000 km2 forest at high, or extreme, risk of fire-induced forest loss, with a further 3 M km2 at risk by the end of the century. This has the potential to degrade or destroy some of the largest remaining intact forests in the world, negatively impact the health and economic wellbeing of people living in the region, as well as accelerate global climate change.


Isolation and characterization of the regulatory HEX2 gene necessary for glucose repression in yeast.
The HEX2 gene which is necessary for glucose repression and is involved in the regulation of hexokinase PII synthesis and maltose uptake, has been cloned by complementation of a hex2 mutant, and selection for restored growth on maltose. Glucose repression in the transformants was like that in the wild type. The HEX2 gene was localized within a 2.15 kb fragment. The restriction map was confirmed by Southern hybridization of genomic DNA. Based on 30 tetrads, the linkage between HEX2 and TRP1 was determined as 10 cM. Plasmid integration directed to the genomic site of the cloned gene also gave a similar linkage distance between the amino acid auxotroph plasmid marker and genomic TRP1. Gene disruption of HEX2 yielded nonrepressible transformants with elevated hexokinase PII activity showing inhibition by maltose; this provides clear evidence that the HEX2 gene has been isolated.


Combined endoscope-assisted translabyrinthine subtemporal keyhole approach for vestibular Schwannoma and auditory midbrain implantation: Cadaveric study.
The combined endoscope-assisted translabyrinthine subtemporal keyhole approach can expose the internal auditory canal, cerebellopontine, and inferior colliculus satisfactorily in the same surgical setting. As a minimally invasive approach, this can be considered an effective method for removal of vestibular schwannoma and auditory midbrain implantation in the same surgical setting, while avoiding retraction of the cerebellum and serious adverse events and complications. Patients with neurofibromatosis type II are the initial candidates for auditory midbrain implantation; the appropriate surgical approach should allow for tumor removal and electrode implantation in the same surgical setting. Here, we demonstrate the possibility of the combined endoscope-assisted translabyrinthine subtemporal keyhole approach to achieve this aim. Five formalin-fixed cadaver heads were used to simulate surgical procedures in 10 sides, by means of microscopy and endoscopy. The relationship between concerned structures was identified. With the help of an endoscope, we exposed the internal auditory canal and cerebellopontine through a translabyrinthine approach and the inferior colliculus through a subtemporal keyhole approach. This double approach can be combined to expose the internal auditory canal and cerebellopontine and inferior colliculus satisfactorily in the same surgical setting. This combined approach can avoid retraction of the cerebellum and reduce serious adverse events and complications.


Husbandry, handling, and nutrition for marmosets.
Marmosets, especially Callithrix jacchus, have become an established part of the laboratory animal community. Information on marmoset life history, behavior, and diet acquired from experience with natural and captive habitats has increased, but the early information from workers with colonies, principally those of tamarins, has led to some common perceptions about how to house, handle, and especially, feed callitrichids that may not apply to marmoset requirements. The availability of commercially produced, almost-complete base diet components and a wider variety of cage construction materials, combined with the recent emphasis on the integration of engineering and performance standards for housing, have made captive life and the implementation of research requirements better for the animals and the people that work with them. We will review some of the routine aspects of husbandry, handling, and nutrition for marmoset monkeys maintained in a research setting.


Choroidal and Retinal Changes After Systemic Adrenaline and Photodynamic Therapy in Non-Human Primates.
To determine the tomographic, angiographic, and histologic changes in the choroid and retina of cynomolgus monkeys after systemic adrenaline and verteporfin photodynamic therapy (vPDT). Six cynomolgus monkeys (12 eyes) were treated with vPDT only (n = 2), adrenaline only for eight weeks (n = 2), adrenaline for eight weeks with vPDT at week 4 (n = 4), and adrenaline for 12 weeks and vPDT at week 8 (n = 4). Spectral-domain optical coherence tomography, angiography, and autofluorescence were performed at baseline and every 14 days thereafter until 28 days after adrenaline therapy or vPDT. Choroid parameters included choroidal thickness (CT) changes and structural changes using semiautomated image binarization. Histology with light and electron microscopy was performed. Adrenaline resulted in subfoveal CT increase at week 4 compared with baseline (3.4%, P = 0.010), with further increase at week 8 (3.9%, P = 0.007). This correlated with choroidal luminal area increase (16.0% at week 8 compared with baseline, P = 0.030). Outer retinal changes included subretinal fluid, ellipsoid zone (EZ) disruption, photoreceptor elongation, and sub/intraretinal bright dots. Hypocyanescent spots surrounded by leakage was observed. Histology showed dilated choroidal vessels, intracytoplasmic vacuoles, and retinal pigment epithelium (RPE) enlarged basal infoldings. The vPDT decreased subfoveal CT at four weeks after vPDT (-7.5%, P = 0.007). This correlated with choroidal stromal area decrease (-18.0%, P < 0.010). Within the treatment spot, there was outer retinal atrophy, EZ disruption, irregular RPE thickening, intense hypoautofluorescence, hyperfluorescence, and hypocyanescence. On histology, there were outer retina, RPE, and choroid changes. Adrenaline induces choroidal vessel dilation and CT increase. The vPDT decreases CT because of a reduction in choroidal stromal component.


Peristaltic transport and mixing of cytosol through the whole body of Physarum plasmodium.
We study how the net transport and mixing of chemicals occur in a relatively large amoeba, the true slime mold Physarum polycephalum. The shuttle streaming of the amoeba is characterized by a rhythmic flow of the order of 1 μm/s in which the protoplasm streams back and forth. To explain the experimentally observed transport of chemicals, we formulate a simplified model to consider the mechanism by which net transport can be induced by shuttle (or periodic) motion inside the amoeba. This model is independent from the details of fluid property as it is based on the mass conservation law only. Even in such a simplified model, we demonstrate that sectional oscillations play an important role in net transport and discuss the effects of the sectional boundary motion on net transport in the microorganism.


Ras/Raf signalling and emerging pharmacotherapeutic targets.
The Ras-Raf-MEK-ERK pathway is a ubiquitously expressed signalling module that regulates the proliferation, differentiation and survival of cells. This pathway features several oncogenes and is deregulated in approximately 30% of all human cancers. Thus, it has emerged as a prime target for antitumour therapy. Drugs targeting Ras, Raf or MEK are currently in clinical trials. They comprise vaccines, isoprenylation inhibitors, antisense compounds and kinase inhibitors. Most are remarkably well tolerated and some show promising efficacy. However, it is not clear which components of this pathway should be targeted and how maximum efficacy can be achieved. This paper reviews the current efforts with an emphasis on new mechanistic and conceptual approaches.


Characterization of Long Non-coding RNA Associated Proteins by RNA-Immunoprecipitation.
With the advances in sequencing technology and transcriptome analysis, it is estimated that up to 75% of the human genome is transcribed into RNAs. This finding prompted intensive investigations on the biological functions of non-coding RNAs and led to very exciting discoveries of microRNAs as important players in disease pathogenesis and therapeutic applications. Research on long non-coding RNAs (lncRNAs) is in its infancy, yet a broad spectrum of biological regulations has been attributed to lncRNAs. RNA-immunoprecipitation (RNA-IP) is a technique of detecting the association of individual proteins with specific RNA molecules in vivo. It can be used to investigate lncRNA-protein interaction and identify lncRNAs that bind to a protein of interest. Here we describe the protocol of this assay with detailed materials and methods.


Subsidized Housing and Health: An Exploratory Study Examining Resident Perspectives on Community Health and Access to Care.
Adequate, safe, and affordable housing is an important determinant of health, yet studies on subsidized housing and health are limited in number and scope. This exploratory survey assessed the health conditions, needs, accessibility of services, and health issues perceived as most important by federally-subsidized affordable housing participants in Virginia. Results for residents of public housing complexes, tenants with housing vouchers, and a nationally representative sample are compared. Findings highlight issues related to cost of care, transportation, medication adherence, depression, and asthma. While housing subsidies are intended to reduce economic burden by enabling residents to use financial resources for other purposes (e.g., preventive health care, access to food), findings suggest that participants continue to experience cost-related barriers and poor health.


Repeatability and Reproducibility of Retinal Blood Flow Measurement Using a Doppler Optical Coherence Tomography Flowmeter in Healthy Subjects.
To evaluate the repeatability and reproducibility of retinal blood flow (RBF) measurements in humans by using new auto-alignment and measurement software in a commercially available Doppler optical coherence tomography (DOCT) system. The DOCT flowmeter assessed the intrasession repeatability and the intersession and interobserver reproducibility of the RBF measurements. For intrasession repeatability, the coefficients of variation (CVs) of five repeated RBF measurements were calculated at the retinal arteries and veins in 20 normal eyes of 20 healthy volunteers. For intersession reproducibility, two sets of three measurements obtained by one observer on 2 different days were compared. For interobserver reproducibility, two sets of three measurements obtained by two observers on the same day were compared. Intraclass correlation coefficients (ICCs) also were used to evaluate the repeatability and reproducibility. The relevance of the DOCT flowmeter and laser Doppler velocimetry (LDV) also was assessed. Regarding intrasession repeatability, the ICC of the RBF exceeded 0.90 in arterioles and venules (ICC: 0.994 and 0.970, respectively). The CVs of the RBF in the arterioles and venules were 6.0% ± 3.4% and 8.8% ± 5.1%, respectively. The intersession and interobserver RBF values had high reproducibility in the arterioles (ICC: 0.980 and 0.993, respectively) and venules (ICC: 0.982 and 0.986, respectively). The RBF measured with the DOCT flowmeter was correlated strongly with LDV in the arterioles (r = 0.76; P < 0.001). The DOCT flowmeter had good reproducibility in the arterioles and venules and precisely measured the RBF as compared to the LDV in the arterioles.


Longitudinal injecting risk behaviours among people with a history of injecting drug use in an Australian prison setting: The HITS-p study.
HCV transmission remains high in prisons globally. Understanding injecting risk behaviours in prisons is crucial to effectively develop and implement HCV prevention programs in this setting including treatment as prevention. HITS-p is a cohort study which enrolled people with a history of injecting drug use in prisons in NSW, Australia from 2005 to 2013. Participants completed an interview at enrolment and follow-up visits to determine injecting behaviours. Generalized estimating equation (GEE) and logistic regression methods were used to assess injecting risk behaviours prior to and following prison entry and to investigate injecting risk behaviours in prison. Overall, 499 participants with a history of injecting drug use were included (median age, 26 years; 65% male). Participants were significantly less likely to inject drugs following incarceration. Among injectors, participants were less likely to inject ≥weekly but more likely to share a needle/syringe. At enrolment, the proportion reporting any injecting, ≥weekly injecting, and needle/syringe sharing in prison was highest among younger individuals. Younger age was associated with both re-initiation and continuation of injecting drug use following prison entry. Among those continuously imprisoned, younger age was associated with increased odds of any injecting, ≥weekly injecting, and sharing a needle/syringe. Upon entry to prison, injecting drug use decreased but syringe sharing increased among injectors. Younger individuals are most likely to exhibit high-risk injecting behaviours in prison. These data highlight the need for improved HCV prevention strategies (including improved needle/syringe access and scale up of HCV therapy) for those at increased risk of HCV transmission in prison, including younger individuals.


Stable (2)H isotope analysis of modern-day human hair and nails can aid forensic human identification.
Continuous-flow isotope ratio mass spectrometry (CF-IRMS) was used to compare (2)H isotopic composition at natural abundance level of human scalp hair and fingernail samples collected from subjects worldwide with interpolated delta(2)H precipitation values at corresponding locations. The results showed a strong correlation between delta(2)H values of meteoric water and hair (r(2) = 0.86), while the corresponding correlation for nails was not as strong (r(2) = 0.6). Offsets of -180 per thousand and -127 per thousand were observed when calculating solutions of the linear regression analyses for delta(2)H vs. delta(18)O correlation plots of hair and nail samples, respectively. Compared with the +10 per thousand offset of the global meteoric water line equation these findings suggested that delta(18)O data from hair and nail would be of limited diagnostic value. The results of this pilot study provide for the first time tentative correlations of (2)H isotopic composition of human hair and nails with local water. Linear regression analyses for measured delta(2)H values of human hair and nails vs. water yielded delta(2)H(hair) = 0.49 x delta(2)H(water) - 35 and delta(2)H(nails) = 0.38 x delta(2)H(water) - 49, respectively. The results suggest that (2)H isotopic analysis of hair and nail samples can be used to provide information regarding an individual's recent geographical life history and, hence, location. The benefit of this technique is to aid identification of victims of violent crime and mass disasters in circumstances where traditional methods such as DNA and fingerprinting cannot be brought to bear (or at least not immediately).


Our experience in the diagnostics of liver and spleen hemangiomas.
We studied the potentials of conventional imaging methods (sonography, computed tomography) and invasive imaging methods (digital subtraction angiography, fine needle biopsy under sonographic guidance) in diagnosing liver and spleen hemangiomas. 384 patients underwent ultrasound investigation for suspected focal lesions of liver and spleen. Hemangioma was diagnosed in 83 patients. Computed tomography with contrast enhancement was performed on 62 of these 83 patients. The diagnosis of hemangioma was confirmed in 38 (61.3%) patients. In 22 patients the combination of sonography and computed tomography failed to provide indubitable diagnosis. Digital subtraction angiography was performed in 11 of them; the remaining 11 patients underwent fine needle biopsy under sonographic guidance. The authors achieve precision in the diagnosis of liver and spleen hemangiomas by employing combinations of above mentioned imaging methods.


Metabotropic glutamate 7 receptor agonist AMN082 inhibits glutamate release in rat cerebral cortex nerve terminal.
AMN082 is a selective metabotropic glutamate mGlu7 receptor agonist reported to exhibit antidepressant activity. Considering that excessive glutamate release is involved in the pathogenesis of depression, the effect of N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082) on glutamate release in rat cerebrocortical nerve terminals and the possible underlying mechanism were investigated. In this study, we observed here that AMN082 inhibited 4-aminopyridine-evoked glutamate release and this phenomenon was blocked by the metabotropic glutamate mGlu7 receptor antagonist MMPIP. Moreover, western blot analysis and immunocytochemistry confirmed the presence of presynaptic metabotropic glutamate mGlu7 receptor proteins. The effect of AMN082 on the 4-aminopyridine-evoked release of glutamate was prevented by chelating the extracellular Ca2+ ions and the vesicular transporter inhibitor; however, the effect of AMN082 was unaffected by the glutamate transporter inhibitor. AMN082 reduced the elevation of 4-aminopyridine-evoked intrasynaptosomal Ca2+ concentration, but did not alter the synaptosomal membrane potential. In the presence of the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker, the adenylate cyclase inhibitor, and the protein kinase A inhibitor, the action of AMN082 on the 4-aminopyridine-evoked glutamate release was markedly reduced. These results suggest that the activation of the metabotropic glutamate mGlu7 receptors by AMN082 reduces adenylate cyclase/protein kinase A activation, which subsequently reduces the entry of Ca2+ through voltage-dependent Ca2+ channels and decreases evoked glutamate release. Additionally, fluoxetine, a clinically effective antidepressant, completely occluded the inhibitory effect of AMN082 on glutamate release, thus indicating the existence of a common intracellular mechanism for these two compounds to inhibit glutamate release from the cerebrocortical nerve terminals.


Studies on in vitro paraquat and diquat removal by activated carbon.
The adsorption characteristics of paraquat and diquat onto activated carbon in vitro were discussed for the primary treatment of acute poisoning by accidental, suicidal or homicidal ingestion of paraquat containing herbicides. Paraquat was adsorbed onto activated carbon more abundantly and more rapidly in physiological saline solution than that in artificial gastric juice and distilled water. Most suitable solvent for paraquat removal by activated carbon was physiological saline solution (0.9% sodium chloride solution). No significant correlation was observed between the ability of paraquat removal and the properties of adsorbent. Paraquat was preferentially adsorbed onto activated carbon in the mixed solution. The adsorption abilities by activated carbon (the removal ratio, the amount adsorbed and the adsorption rate) for paraquat were larger than those for diquat, and it was enhanced by added sodium chloride and added magnesium sulfate. Enhancing effect for adsorption removal was proportional to the saline concentration. As addition of salts into carbon suspension enhanced the adsorption ability, it will contribute to the effective treatment of acute poisoning.


Is the decrease of cardiovascular mortality in Poland associated with the reduction of global cardiovascular risk related to changes in life style?
After an ascending trend of cardiovascular mortality, which was observed up to the sixties, there was a declining tendency in western countries thereafter. The decrease in mortality rates in Poland has been noticed since 1991. There is an uncertainty whether this improvement in prognosis was only due to the improvement in health care level or was accomplished, to some extent, by population life style changes. To assess whether the decrease in cardiovascular mortality in Poland was accompanied by a simultaneous reduction in global cardiovascular risk profile. The study was based on screened random samples from the Warsaw population aged 35-64 years, who were examined in the years 1984 (2646 subjects), 1988 (1433 subjects), 1993 (1539 subjects) and 2001 (853 subjects). The group evaluated in 1984 was followed up for 10 years with all fatal events recorded (364 deaths were registered including 166 cardiovascular deaths). The model of 10 years probability of total and cardiovascular death was developed, which was based on 11 risk factors (age, smoking cigarettes, systolic blood pressure, pulse pressure, ratio of total cholesterol/HDL-cholesterol, triglyceride, symptoms of coronary heart disease or heart failure, death of mother before 65 or death of father before 55 years due to myocardial infarction or stroke, energy in daily food intake and percentage of energy derived from saturated fatty acids). This model was applied to assess the probability of deaths between years 1984 and 2001, utilising data from screenings. The probability of death (in %) decreased from 1984 to 2001 by 11% in men. However, it remained stable for women. On the other hand the probability of cardiovascular death decreased by 25% and 33%, respectively. The main role in global risk decrease was played by beneficial trends in mean systolic blood pressure (in both genders) and percentage of smokers in men. Modification of life style influencing risk factors profile decreased the probability of death in the Warsaw population, correlating with changes in mortality rates.


Cardiac pacing and defibrillation in children and young adults.
The population of children and young adults requiring a cardiac pacing device has been consistently increasing. The current generation of devices are small with a longer battery life, programming capabilities that can cater to the demands of the young patients and ability to treat brady and tachyarrhythmias as well as heart failure. This has increased the scope and clinical indications of using these devices. As patients with congenital heart disease (CHD) comprise majority of these patients requiring devices, the knowledge of indications, pacing leads and devices, anatomical variations and the technical skills required are different than that required in the adult population. In this review we attempt to discuss these specific points in detail to improve the understanding of cardiac pacing in children and young adults.


Drug-Induced Liver Injury during Consolidation Therapy in Childhood Acute Lymphoblastic Leukemia as Assessed for Causality Using the Updated RUCAM.
The presence of serious toxicities is a major problem in the treatment of childhood acute lymphoblastic leukemia (ALL). The objective of this research is to evaluate drug-induced liver injury (DILI) during consolidation therapy in childhood ALL. Clinical data of pediatric patients who received consolidation therapy between August 2012 and July 2018 were collected. Characteristics (incidences and patterns) of DILI at different stratifications were determined. Risks of DILI were evaluated using binary logistic regression analysis. Drug causality assessment was carried out by the updated Roussel Uclaf Causality Assessment Method (RUCAM). Patients with high risk (HR) and standard risk (SR)/intermediate risk (IR) received 270 and 1539 courses of consolidation therapy, respectively; among these courses, 15 (5.6%) and 38 (2.5%) developed DILI. The occurrences of DILI in SR/IR patients were primarily associated with age (≤5.2 years), treatment course (≥5), and baseline serum parameters before treatment (cystatin C > 0.79 mg/L, albumin ≤45 g/L, and gamma-glutamyl transpeptidase (GGT) > 17 U/L). The ROC curve generated using the parameters assigned to specific values achieved an area under the curve (AUC) of 0.846 (95% CI 0.827-0.863) with a cutoff value of 3, and the sensitivity and specificity were 94.7% and 62.3%, respectively. For HR patients, a decrease in baseline albumin and elevation of baseline liver enzymes (GGT and aspartate aminotransferase) were observed in DILI cases compared with the non-DILI subjects. In the SR/IR group with DILI, the causality gradings for high-dose methotrexate (HD-MTX) were highly probable in 5 (13.2%) cases, probable in 31 (81.6%) cases, and possible in 2 (5.3%) cases. Among the DILI cases in HR-1, HR-2, and HR-3 groups, high causality gradings (probable + highly probable) were detected in "100% of HD-MTX + 57% of high-dose cytarabine (HD-Ara-C)," "100% of HD-MTX + 20% of pegylated asparaginase (PEG-ASP)," and "100% of HD-Ara-C + 33.3% of PEG-ASP," respectively. Incidence of DILI in HR patients was significantly higher than that in SR/IR patients. A number of potential risk factors were identified, among which the preexisting liver conditions were suggested as shared risk factors in all stratification groups. HD-MTX, HD-Ara-C, and PEG-ASP were the main causative agents of DILI. The knowledge generated from this study will be helpful for understanding characteristics of DILI during consolidation treatment in childhood ALL.


Acute lower limb ischemia in a young woman with arterial hypoplasia: a case report.
The most frequent causes for acute limb ischemia are arterial embolism, thrombosis (mainly in patients with atherosclerosis), and traumatic arterial injuries. Rarely, acute limb ischemia may be caused by the arterial spasm, when all other causes can be excluded. We present a case of a young woman with acute ischemia of her right lower extremity with diagnosed arterial hypoplasia in the calf. The suspected cause of the ischemia was a spasm of a single artery of the limb. Diagnostic procedures and treatment as well as differential diagnosis are discussed.


Morphometric analysis of the location and activity of cytokines in the tissue implant response.
The objective of this investigation was to evaluate the location and activity of cytokines in the fibrous tissue surrounding tricalcium phosphate (TCP) implants loaded with androgenic hormones. Sixteen animals in four experimental groups (n = 4/group) were implanted with one TCP implant each: Group I (control), Group II (testosterone), Group III (dihydrotestosterone), and Group IV (androstenedione). At 90 days post-implantation, the fibrous tissue surrounding the implants were evaluated following staining with antibodies to IL-1ß, IL-2, IL-6, and TNF?. Data were collected on the presence and distribution of cytokines within the fibrous tissue surrounding all four groups. IL-1ß was primarily found intercellular and associated with fibroblasts and macrophages of Groups I-III. IL-2 was present in the extracellular matrix and was sporadically found on the surface of macrophages in Groups I-III. IL-6 was found primarily concentrated in the fibroblast and collagen rich portions of the fibrous tissue matrix in Groups I-III. TNF-? was present in the extracellular matrix of the fibrous tissue of all four groups and was strongly associated with fibroblast and macrophage rich areas. The results of this study confirm activity of cytokines on target cells and indicate their actions may vary in their effect within the fibrous tissue surrounding TCP implants loaded with androgens.


Teicoplanin and its influence on Staphylococcus aureus ultrastructure.
Teicoplanin, a glycopeptide antibiotic chemically related to the vancomycin-ristocetin group of antibiotics, has been shown to be active against gram-positive bacteria. Binding of teicoplanin by actively growing bacteria leads to morphological damage to the cell surface in staphylococci, as largely shown by transmission and scanning microscopy results.


Acellular dermal matrix allograft. The results of controlled randomized clinical studies.
The aim of this presentation was to discuss the effectiveness of the acellular dermal matrix in root coverage therapy and in alveolar ridge augmentation, based on three controlled randomized clinical trials conducted by our research team (Novaes Jr et al., 2001; Barros et al., 2005; Luczyszyn et al., 2005). The first and second studies highlight the allograft's performance in the treatment of gingival recession. In both studies, clinical parameters were assessed prior to surgery and 6 or 12 months post-surgery. The first one compared the use of the acellular dermal matrix with the subepithelial connective tissue graft and showed 1.83 and 2.10 mm of recession reduction, respectively. Because no statistically significant differences between the groups were observed, it was concluded that the allograft can be used as a substitute for the autograft. In the second study, a new surgical approach was compared to a conventional surgical procedure described by Langer and Langer in 1985. A statistically significant greater recession reduction favoring the test procedure was achieved. The percentage of root coverage was 82.5% and 62.3% for test and control groups. Thus the new technique was considered more suitable for the treatment of gingival recessions with the allograft. Finally, the third study evaluated the allograft as a membrane, associated or not with a resorbable hydroxyapatite in bone regeneration to prevent ridge deformities. In one group the extraction sockets were covered only by the allograft and in the other, the alveoli were also filled with the resorbable hydroxyapatite. After six months, both treatments were able to preserve ridge thickness, considering the pre-operative values. In conclusion, no adverse healing events were noted with the use of allograft in site preservation procedures, and sites treated with the combination of allograft plus resorbable hydroxyapatite showed significantly greater ridge thickness preservation at six months when compared to sites treated with allograft alone (6.8 +/- 1.26 and 5.53 +/- 1.06 respectively).


Density and hydration of fresh and fixed human skeletal muscle.
The maximum tetanic tension of skeletal muscle (P(0)) is often estimated based on calculation of physiological cross-sectional area (PCSA). PCSA depends on muscle volume, pennation angle, and fiber length. Studies documenting PCSA in fixed human muscles usually compute muscle volume by dividing muscle mass by density. These studies use a density value of 1.0597 g/cm(3), which was originally based on unfixed rabbit and canine muscle tissue. Due to the dehydration effects of different fixation methods, the variable hydration that occurs when fixed tissue is stored in buffered saline, and the potential for species-specific muscle density, this value may be incorrect and an accurate value for fixed human muscle density is needed. To obtain an accurate density and water content values, 4% formaldehyde-fixed (n=54) and 37% formaldehyde-fixed (n=54) cadaveric human muscle samples were divided into 6 groups (0, 6, 12, 18, 24, or 30 h) for hydration in phosphate buffered saline (PBS). Measurements of volume, water content, and mass were made enabling calculation of muscle density. Additionally, water content was measured in living muscle (n=4) to determine the appropriate hydration time in PBS. Comparisons among groups demonstrated a significant increase in muscle water content and muscle volume over time, reaching living tissue levels after 24h, but, interestingly, the hydration process did not affect muscle density. These data yield a density value (mean+/-SE) of 1.112+/-0.006 g/cm(3) in 4% formaldehyde-fixed muscle and 1.055+/-0.006 g/cm(3) in 37% formaldehyde-fixed muscle. These results indicate that the use of inappropriate hydration times or density values can produce PCSA errors of 5-10%.