Disease activity, handgrip strengths, and hand dexterity in patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the hand joints and leading to impairment in hand functions. Evaluation of functional impairment is necessary for assessing patient's quality of life, disease activity, and treatment outcome. To date, many scientific studies assessed the disease activity of patients with RA, but little attention has been carried out to assess these patients' hand functions and dexterity. The purposes of this study were to determine the clinical relevance of the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), hand dexterity with the Purdue Pegboard Test (PPT), and handgrip strength and pinch strengths of RA patients and to look into their relation between each other. A prospective trial was performed in women with RA who were followed at the physical medicine and rehabilitation department of our university hospital. Eighty-two women between the ages of 18 and 70, with a diagnosis of RA according to the 2010 American College of Rheumatology/the European League Against Rheumatism (ACR/EULAR) criterion, were recruited to the study. The Disease Activity Scores were determined by using Disease Activity Score-28 (DAS-28). Handgrip strength was measured with a Jamar dynamometer, and lateral, palmar, and tip pinch strengths were measured by a pinchmeter. Hand functions were evaluated with the PPT, and functional outcomes were assessed with the QuickDASH questionnaire. The mean age of the study group was 49.27 ± 10.69 years. The average values of DAS-28 and the QuickDASH values were found to be 4.22 ± 1.28 and 38.33 ± 19.78, consecutively. High correlation was observed between DAS-28 and the QuickDASH values (p < 0.001). The mean grip strengths in both hands were significantly correlated with the QuickDASH values (p < 0.001), and also, DAS-28 values were very significantly correlated with the mean grip strength in the dominant hand (p < 0.001) and in the nondominant hand (p < 0.01). The mean lateral pinch strengths in both hands were correlated statistically significantly with DAS-28 and the QuickDASH scores (p < 0.001). The mean tip pinch strengths in both hands were correlated with DAS-28 scores, but correlation with the QuickDASH scores was seen just in the dominant hand (p < 0.05). There was no correlation between palmar pinch strengths in both hands with the DAS-28 and QuickDASH scores (p > 0.05). DAS-28 was correlated with PPT performance on the dominant hand (p < 0.05), but there was no correlation with the nondominant hand, both hands, and assembly (p > 0.05). The QuickDASH values were not correlated with all PPT performances (p > 0.05). Handgrip strengths of both hands were positively correlated with the PPT performances (p < 0.05). In conclusion, we determined that handgrip strengths were significantly related to disability and disease activity in the RA patients in our study. The QuickDASH is practical to use in clinical practice, and positively correlates with the disease activity. Dexterity measurements with PPT in the RA patient group were found practical and effective in our study. As a result, we can suggest using QuickDASH questionnaire for functional outcomes, handgrip strength measurements for assessment of hand disability and functional impairments, and also dexterity measurements even in patients with low disease activity.


The varying effects of antibiotics on gut microbiota.
Antibiotics are lifesaving therapeutic drugs that have been used by human for decades. They are used both in the fight against bacterial pathogens for both human and for animal feeding. However, of recent, their effects on the gut microbial compositions and diversities have attracted much attention. Existing literature have established the dysbiosis (reduced diversity) in the gut microbiota in association with antibiotic and antibiotic drug doses. In the light of spelling out the varying effects of antibiotic use on gut microbiota, this review aimed at given an account on the degree of gut microbial alteration caused by common antibiotics. While some common antibiotics are found to destroy the common phyla, other debilitating effects were observed. The effects can be attributed to the mode of mechanism, the class of antibiotic, the degree of resistance of the antibiotic used, the dosage used during the treatment, the route of administration, the pharmacokinetic and pharmacodynamics properties and the spectrum of the antibiotic agent. Health status, stress or the type of diet an individual feeds on could be a great proportion as confounding factors. While it is understood that only the bacterial communities are explored in the quest to establishing the role of gut in health, other gut microbial species are somehow contributing to the dysbiosis status of the gut microbiota. Until now, long term natural fluctuations like diseases outbreaks and mutations of the strain might as well rendered alteration to the gut independent of antibiotic treatments.


Investigation of spectroscopic and proteomic alterations underlying prostate carcinogenesis.
Prostate cancer (PCa) treatment remains challenging, especially in advanced stages, where the lack of sensitivity and specificity of available biomarkers makes it difficult to establish an accurate prognosis. Therefore, it is imperative to study PCa biology to identify key molecules that can improve PCa management. In this study, eight prostate tumor tissues and paired normal tissues were analyzed using two approaches-Fourier-transform infrared (FT-IR) spectroscopy for spectroscopic profiling of biomolecules and antibody microarray for signaling proteins-with the main goal of identifying metabolic and proteomic changes that enable the distinction between normal and tumor conditions. Principal component analysis of FT-IR spectra revealed different spectroscopic signals for each condition. The most relevant changes in prostate tumor tissues identified by FT-IR were dysregulation in lipid metabolism, lower polysaccharide and glycogen content, higher nucleic acid content, and increased protein phosphorylation. Using an antibody microarray, 42 proteins were identified as differentially regulated between the two conditions; 14 of those revealed changes in their phosphorylation status. These proteins include transcription factors and kinases and constitute a highly-interconnected interaction network. Altogether, our data reveal metabolic and proteomic alterations that may be of interest in future translational studies aimed at establishing PCa prognosis and treatment. SIGNIFICANCE: Prostate tumor tissues and adjacent benign tissues were analyzed using two approaches-Fourier-transform infrared (FT-IR) spectroscopy for biomolecules and an antibody microarray for signaling proteins, which allowed to identify a panel of metabolic and proteomic alterations that may be of interest in future translational studies to enable the distinction between normal and tumor conditions.


Spatial ability and home-range size: examining the relationship in Western men and women (Homo sapiens).
In mammals, spatial sex differences may have coevolved with sex differences in the size of home ranges. This study first evaluated whether, in keeping with most mammals and traditional human (Homo sapiens) societies, home ranges are larger in male than in female Westerners. Second, it established whether navigation patterns are associated with a broader set of spatial abilities in men than in women. Results showed that current male home ranges surpass female home ranges. Ranging was also positively correlated with achievement in tests of mental rotation, surface development, and location memory among men only, whereas it was associated with embedded figures scores in both sexes. Overall, these findings substantiate the adaptive role of several spatial sex differences in humans.


Meaning of food in childhood obesity: an exploratory study in a chinese family context.
This study aimed to examine the relational meaning of food, based on the results of a qualitative study of eight obese children (six male and two female) and their families in a Chinese society in Hong Kong. The children range in age from 7 to 13. Findings reveal the important bonding function of food in family relationships. Two clinical themes were identified from the data: (1) food bonding nurturer and obese child; (2) eating and the bonding relationship with extended family. Putting a child on a diet was found to disrupt the bonding between the nurturers and the obese child. Power struggles over the loyalty of the child in food provision were also observed. Implications for practice are discussed.


Helicobacter pylori seroprevalence in patients with coronary artery disease.
Recent studies have suggested that chronic infections such as Helicobacter pylori may be a risk factor for coronary artery disease (CAD). The aim of thIS study was to investigate the seroprevalence of H. pylori in patients with CAD. We enrolled 151 patients with CAD (93 men and 58 women, aged 48.1 +/- 17.3 years [mean +/- SD]) and 149 control subjects matched by age and sex (90 men and 59 women, aged 51.4 +/- 13.9 years). An enzyme-linked immunosorbent assay immunoglobulin (Ig) G test for H. pylori diagnosis was performed on all enrolled subjects (CAD patients and controls). Ninety-one of 151 patients with CAD (60.2%) and 86 of the 149 subjects in the control group (57.7%) were H. pylori positive (P > 0.05). H. pylori infection rates were similar in patients with CAD and control groups. The main conclusion of this study is that H. pylori infection is not a risk factor for developing CAD. Further studies should be undertaken to confirm our results.


[Resources of medicinal pteridophyta in Fengyang Mountain and Baishanzu Nature Reservation].
Natural environment of Fengyang Mountain and Baishanzu Nature Reservation is superiority. The vegetation is preserved well and the plant resources is rich. There are 79 species medicinal pteridophyta in this area. According to potency, it can be divided into 16 types, such as medicines for relieving exterior syndrome, medicines for clearing away heat, antirheumatic, medicines for inducing diuresis, medicines for expelling the parasites, hemostasis medicines, medicines for activating blood circulation to remove blood stasis, medicines for restoring vital energy, medicines for calming the liver to stop the wind, etc.


The computation of ICRP dose coefficients for intakes of radionuclides with PLEIADES: biokinetic aspects.
The ICRP has published dose coefficients for the ingestion or inhalation of radionuclides in a series of reports covering intakes by workers and members of the public including children and pregnant or lactating women. The calculation of these coefficients conveniently divides into two distinct parts--the biokinetic and dosimetric. This paper gives a brief summary of the methods used to solve the biokinetic problem in the generation of dose coefficients on behalf of the ICRP, as implemented in the Health Protection Agency's internal dosimetry code PLEIADES.


How Institution of the Sup-ER Protocol in a Clinic Changed Procedure Patterns in Upper Brachial Plexus (Erb's Type) Birth Injuries.
For children with upper brachial plexus birth injury (BPBI; C5, C6, ±C7 roots), most clinics first recommend nonsurgical treatment followed by primary and/or secondary surgical interventions in selected patients. Since 2008, we have used an infant shoulder repositioning protocol (supination-external rotation [Sup-ER]) designed to prevent shoulder internal rotation contracture and its potential effects on the shoulder joint. This study characterizes our clinic's current choice, number, and timing of primary and secondary procedural interventions (including Botox) and compares Sup-ER protocol patients with those of our historical controls. The records of all patients with upper BPBI who underwent procedures from 2001 to 2018 were retrospectively reviewed and grouped into a historical (2001-2007, n = 20) and recent (2008-2018, n = 23) cohort. Patient demographics, procedure types and timing, and functional outcomes were collected and analyzed. Since the 2008 institution of the Sup-ER protocol, fewer brachial plexus exploration and grafting (BPEG) surgeries were performed and none in later infancy, where nerve transfers were preferred. There were more and earlier Botox injections. There were fewer tendon transfers, and the preoperative indications were from a higher level of function. We now see fewer indications for BPEG surgeries overall. After the 3-month-age group, more direct nerve transfers are indicated instead of the BPEG surgery if nerve surgery is required at all. Shoulder tendon transfer rates have decreased. Humeral osteotomies are not seen in our recent group. Glenoid osteotomies within tendon transfers are rare in both groups.


The mammalian target of the rapamycin (mTOR) kinase pathway: its role in tumourigenesis and targeted antitumour therapy.
The mammalian target of rapamycin (mTOR) is a kinase responsible for mitogen-induced cell proliferation/survival signaling. Its activation in response to mitogens leads to a cell-cycle progression from G1 to S phase. mTOR controls the activation of ribosomal protein translation and the initiation of cap-dependent translation. A role of mTOR signaling pathway dysregulation in tumourigenesis is postulated. mTOR and pathways upstream of this kinase were found to be frequently upregulated in neoplastic diseases. Therefore, it is also an attractive target for antitumour therapy. Several mTOR inhibitors were developed, including rapamycin and its analogues: CCI-779, RAD001 and AP23573. After promising phase I studies, their potential clinical significance is currently under evaluation in several phase II-III trials on patients with solid tumours and some hematological malignancies.


The Liverpool Peritonsillar abscess Score: Development of a predictive score through a prospective multicentre observational study.
While uncommon in the population at large, peritonsillar abscess (PTA) is a common subject of ENT referrals. Missed or uncertain diagnosis is a source of concern for non-specialist referrers. In line with the NHS England Second Sepsis Action Plan, we aimed to develop a predictive score for the presence of PTA. This would help to improve non-specialist colleagues' diagnostic certainty as well as to support ENT surgeons' triage of these referrals. Prospective, multicentre observational study. Primary and secondary care. Patients >16 years with symptoms of sore throat. We prospectively collected comprehensive data on patient demographics, symptoms and clinical status. We documented whether the patient had aspiration-proven PTA or not. We performed binary logistic regression analysis, iterative development of a predictive score which we validated internally. 100 patients were included (46 PTA and 54 tonsillitis). Five variables added significantly to the logistic regression model: unilateral sore throat; trismus; male gender; pharyngeal voice change; and uvular deviation. Using the odds ratio outputs, we developed the Liverpool Peritonsillar abscess Score (LPS) iteratively. We validated the latest (third) iteration of the LPS internally (ie, on the same sample), yielding sensitivity 96%; specificity 85%; positive predictive value 85%; and negative predictive value 96%. The area under the receiver operating characteristics (AUROC) curve was 0.970. We have developed the first predictive score for PTA based on symptoms and signs that do not require the user to have specialist experience. Its high negative predictive value may be particularly helpful to non-specialist colleagues.


Acute compartment syndrome in the thigh. A case report and a review of the literature.
Compartment syndrome in the thigh is an uncommon condition, and acute compartment syndrome without an associated fracture is even less common. An 18-year-old male developed an acute anterior compartment syndrome in the thigh from a contusion without an associated fracture. This syndrome was treated successfully with a fasciotomy.


Conditional fluorescent mouse translocation reporters for ERK1/2 and AKT signaling.
Understanding how cells activate intracellular signaling pathways in response to external signals, such as growth factors, is a longstanding goal of cell and developmental biology. Recently, live-cell signaling reporters have greatly expanded our understanding of signaling dynamics in response to wide-ranging stimuli and chemical or genetic perturbation, both ex vivo (cell lines) and in vivo (whole embryos or animals). Among the many varieties of reporter systems, translocation reporters that change sub-cellular localization in response to pathway activation have received considerable attention for their ease of use compared to FRET systems and favorable response times compared to transcriptional reporters. We reasoned that mouse reporter lines expressed in a conditional fashion would be a useful addition to the arsenal of mouse genetic tools, as such lines remain undeveloped despite widespread use of these sensors. We therefore created and validated two novel mouse reporter lines at the ROSA26 locus. One expresses an ERK1/2 pathway reporter and a nuclear marker from a single transcript, while the second additionally expresses an AKT reporter in order to simultaneously interrogate both pathways.


Surface functions during mitosis. II. Quantitation of pinocytosis and kinetic characterization of the mitotic cycle with a new fluorescence technique.
The profound depression of fluid pinocytosis observed in mitotic cells (Berlin, R. D., et al. 1978. Cell. 15:327--341) is documented by quantitative microspectrofluorimetry of fluorescein-labeled dextran uptake in single cells. In J774.2 macrophages, fluid pinocytosis is reduced 30-fold during mitosis. The depression develops within 30 s of entry into prophase and recovers with equal rapidity upon emergence from telophase into G1. This characteristic pattern of fluid pinocytosis forms the basis of a new method for detailed kinetic analysis of the duration of mitosis and its phases. The analysis is applied to the J774.2 macrophage cell line but should be generally applicable to other lines. Effects of ouabain and colchicine on the length of mitosis and its phases are evaluated, revealing a selective prolongation of metaphase by ouabain and suggesting a role for microtubules in the transition from G2 into mitosis.


Abnormal uterine stromal and glandular function associated with maternal reproductive defects in Hoxa-11 null mice.
Here we describe in detail both the expression of Hoxa-11 in the wild-type mouse uterus and the defects resulting in maternal reproductive failure of Hoxa-11 null female mice. The Hoxa-11 gene is expressed at peak levels in uterine stromal cells during metestrus. Hoxa-11 transcripts were induced beginning on Day 2 of gestation in the stromal cells underlying the uterine epithelium and appeared in the secondary decidual zone between Days 6 and 8 of gestation. At early gestational stages, stromal, decidual, and glandular cell development were deficient in Hoxa-11 null uteri in comparison to wild-type as assessed by histology and immunohistochemical localization of the decidual cell marker epitope, stage-specific embryonic antigen-3 (SSEA-3). Both steroid-induced uterine stromal and glandular cell proliferation as well as oil-induced stromal decidualization after induction of pseudopregnancy were deficient in mutant uteri. Moreover, both Western blotting and immunohistochemistry demonstrated that the burst of glandular leukemia inhibitory factor (LIF) found in normal pregnant uteri at Day 4.5 of gestation was absent in Hoxa-11-deficient uteri. The LIF burst was also not observed in the uteri of bilaterally ovariectomized, hormonally stimulated Hoxa-11 mutants. These results demonstrate that the Hoxa-11 gene is required for normal uterine stromal cell and glandular differentiation during pregnancy, as is the presence of the steroid-induced glandular LIF burst initiating embryo implantation.


Pregnancy-related carpal tunnel syndrome.
Clinical and electrophysiological features were studied in 52 cases of carpal tunnel syndrome (CTS) associated with 30 pregnancies. The duration of symptoms was less than 3 months before electrodiagnosis was performed. This study revealed a higher incidence of persistent, painful diurnal symptoms in pregnancy-related CTS (PRCTS) than in idiopathic CTS. PRCTS usually occurs for the first time (de novo) (24/30 cases), in primigravidas (15 cases) as well as multigravidas. The onset of symptoms was in the first or second trimester in 11 women, the third trimester in 12 women, or the post-partum period in seven women. Nerve conduction studies demonstrated evidence of an acute median nerve lesion at the wrist with motor and/or sensory conduction blocks in 20/30 women and severe denervation signs in five women.


['The man with the withered hand': iconography of the saturnine palsy?]
The synoptic gospels tell about a man who cannot extend his hand, that appeared dried. The description is consistent with radial palsy. Christian artists depicted this gospel story producing a rich material, unexplored from the medical point of view. To analyze the mentioned iconography verifying the depicted lesions and their possible causes. Six representations of the evangelical text pertaining to the period comprehended between 10th and 17th centuries were selected. Four belong to illuminated gospels, one is a mosaic and the other one is a fresco. In three of them the figure with the palsy hand appeared holding the affected member with the opposite hand; another one has a foot drop. The description of postures that are characteristic of extensor palsies points out that these artists must have known real patients. Saturnism, frequent in Europe during the period in which these works were created, was probably the cause of the paralysis in these cases. Another hypothesis was that the artists could have suffered themselves saturnism, caused by manipulating paints with high lead content; this could not be confirmed. The iconographies of 'the man with the withered hand' are realistic representations of motor paralysis consistent with saturnine neuropathy. These works preceded for a long time the best medical descriptions of such condition.


[Contribution of ultrasonography in thyroid diseases. Apropos of 100 cases].
Thyroid disease is a very common disease, essentially affecting women, and raises diagnostic and therapeutic problems. The objective of this study was to specify the value of ultrasonography in the diagnosis and aetiological orientation of these lesions, based on a retrospective study of 100 patients. The results of ultrasonography were compared to the histological results. The aetiologies detected were dominated by benign lesions, particularly adenomas (56 cases), dystrophic goitres (32 cases) and cancers (7 cases). Ultrasonography allowed the detection of clinically impalpable nodules with no isotope scan signs in 11% of cases. The ultrasonographic appearance of benign nodules was variable. Solitary nodules were detected in 63 cases. They were hyperechoic in 15 cases, isoechoic in 8 cases, cystic in 9 cases, and mixed in 31 cases. A peripheral clear halo was revealed in 25 cases and macrocalcifications were present in 17 cases. Malignant lesions were visualized in 7 cases and were solitary in 5 cases. Solitary lesions had a hypoechoic echostructure in 1 case, an isoechoic echostructure in 2 cases and a mixed echostructure in 2 cases. The margins were poorly demarcated in 3 cases, and circumscribed without peripheral halo in 2 cases. Cervical lymphadenopathy was detected in 2 cases. Graves' disease, diagnosed in 2 patients, showed a diffuse hypoechoic appearance of the entire thyroid gland. Ultrasonography is a sensitive morphological method for the diagnosis of thyroid lesions. A detailed and precise analysis of the ultrasound signs of the lesion can suggest that benign or malignant nature of the lesion, which can be completed by Doppler-ultrasound and especially ultrasound-guided needle biopsies.


The role of reactive oxygen species and capsaicin-sensitive sensory nerves in the pathomechanisms of gastric ulcers induced by stress.
Gastric microcirculation plays an important role in the maintenance of the gastric mucosal barrier and mucosal integrity. Sensory nerves are involved in the regulation of mucosal blood circulation and mucosal defense. Therefore, the ablation of these nerves by neurotoxic doses of capsaicin provides the possibility of determination of their role in gastric mucosal integrity. Stress ulceration represents a serious gastric lesions. Results of our previous experiments have indicated that water immersion and restraint stress (WRS) led to increased oxidative metabolism. Ablation of sensory nerves by high doses of capsaicin retards healing of gastric ulcers, but the role of reactive oxygen species (ROS) in the healing process has been little studied. Therefore, the aim of our present investigations was to determine the participation of ROS in sensory nerve activity during WRS. Experiments were carried out on 90 male Wistar rats and the area of gastric lesions was measured by planimetry. Colorimetric assays were used to determine gastric mucosal levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), as well as superoxide dismutase (SOD) activity. We demonstrated that inactivation of sensory nerves resulted in magnification of gastric mucosal damage induced by the WRS. In this process, oxidative stress, as reflected by an increase of MDA and 4-HNE tissue concentrations (an index of lipid peroxidation), as well as decrease of SOD activity, could play an important role. Aspirin, applied in a low dose, exerts a protective activity, possibly due to its metabolites, which possess the anti-oxidant and ROS scavanging properties. Pentoxyfilline-induced gastroprotection and hyperemia depends upon attenuation of the oxidative stress. This protection and hyperemia were, at least in part, attenuated by ASA.


Enhancing case management through computerized patient files.
The need for developing an organizational system for managing a large patient specialty population prompted the use of a computerized data entry and retrieval system. The use of a computerized system has facilitated patient case management, chart organization, and development of accessible data for research. Patient data fields (topic headings) are used for: (1) storing specific categories of patient data, (2) compiling lists for management and research, and (3) referring physician and patient/family contact information. Various lists can be compiled from the field data base in order to develop research and patient management lists. Patient management lists are used to track a patient's progress, provide quality assurance of care, and contribute researchable data. Also, patient information can be transferred automatically from the computerized daily management system into a computerized form letter. Individualized patient letters may be generated. Laboratory and test information from the last clinic or hospital visit can be mailed to families along with a handwritten personalized interpretation of their results by the CNS or physician.


Scaling range sizes to threats for robust predictions of risks to biodiversity.
Assessments of risk to biodiversity often rely on spatial distributions of species and ecosystems. Range-size metrics used extensively in these assessments, such as area of occupancy (AOO), are sensitive to measurement scale, prompting proposals to measure them at finer scales or at different scales based on the shape of the distribution or ecological characteristics of the biota. Despite its dominant role in red-list assessments for decades, appropriate spatial scales of AOO for predicting risks of species' extinction or ecosystem collapse remain untested and contentious. There are no quantitative evaluations of the scale-sensitivity of AOO as a predictor of risks, the relationship between optimal AOO scale and threat scale, or the effect of grid uncertainty. We used stochastic simulation models to explore risks to ecosystems and species with clustered, dispersed, and linear distribution patterns subject to regimes of threat events with different frequency and spatial extent. Area of occupancy was an accurate predictor of risk (0.81<|r|<0.98) and performed optimally when measured with grid cells 0.1-1.0 times the largest plausible area threatened by an event. Contrary to previous assertions, estimates of AOO at these relatively coarse scales were better predictors of risk than finer-scale estimates of AOO (e.g., when measurement cells are <1% of the area of the largest threat). The optimal scale depended on the spatial scales of threats more than the shape or size of biotic distributions. Although we found appreciable potential for grid-measurement errors, current IUCN guidelines for estimating AOO neutralize geometric uncertainty and incorporate effective scaling procedures for assessing risks posed by landscape-scale threats to species and ecosystems.


[Projective methods and dangerous behavior].
The prediction of dangerousness by projective methods deals with some specific problems related to the bound between projective material and overt behaviour.


Epidemiologic features of 348 children with hepatitis C virus infection over a 30-year period: a nationwide survey in Japan.
Although the epidemiology of hepatitis C virus (HCV) infection among children may be rapidly changing, few reports have characterized large nationwide cohorts of children with HCV infection. We, therefore, sought to clarify the epidemiology and natural history of HCV infection in Japanese children born over the last three decades. Sixty-five pediatric centers retrospectively and prospectively recruited consecutive, otherwise-healthy HCV-infected children born during 1986 to 2015. Entry criteria were met by 348 children. Age at initial diagnosis of infection has decreased significantly in recent years. Cirrhosis and hepatocellular carcinoma were not identified. Prevalence of spontaneous clearance and of interferon treatment with/without ribavirin were 9 and 54%, respectively. Maternal transmission has increased significantly, representing over 99% of cases in the last decade. No transfusion-related cases have been seen after 1994. HCV genotype 2 has increased to become the most prevalent in Japanese children. Histopathology examination of liver specimens showed no or mild fibrosis in most children with chronic hepatitis C; none showed cirrhosis. This largest nationwide cohort study of Asian children with HCV infection spanned the last three decades. None of these Japanese children developed cirrhosis or hepatocellular carcinoma. Maternal transmission increased to account for 99% of cases during the last decade. Genotype 2 now is most prevalent in these children. Histopathologically, most children with chronic hepatitis C showed mild fibrosis or none.


[Some technical problems in three-dimensional cephalometrics].
Two-dimensional(2D)cephalometrics is an important diagnostic technique in dentistry. Three-dimensional(3D)cephalometrics is becoming a hot point along with the popularity of cone-beam CT(CBCT). However, the 3D cephalometric technique, like 2D cephalometric technique, there are many technical problems needed to be solved. In this article, several topics, including multi-source of 3D cephalometrics, the head position in 3D cephalometrics, the difficulty of landmark indication, norms for 3D cephalometrics and superimposition in 3D imaging, are discussed.


Six groups of double-stranded RNA mycoviruses.
Six groups of double-stranded (ds) RNA mycoviruses have been proposed. The main characteristics which define a group are described, and the properties of members and probable members of each group are tabulated. Possibilities for organization of the groups into families, genera and species are discussed. The classification scheme could ultimately accommodate the majority of the well-characterized dsRNA mycoviruses.


Coronal leakage in teeth root-filled with gutta-percha and two different sealers after long-term storage.
This in vitro study investigated the effect of long-term storage on the coronal leakage of a microbial marker in teeth root-filled with lateral condensation of cold gutta-percha and one of two sealers. Sixty single-rooted teeth were prepared chemomechanically to a size 40 master apical file. The teeth were divided into two groups of 20 teeth each and obturated with gutta-percha using either Apexit or Tubliseal EWT sealer. The teeth were stored for 6 months in artificial saliva and tested for leakage using a marker consisting of Anaerobic streptococci and Prevotella intermedia. The teeth were checked for bacterial leakage daily for 90 days. All positive control teeth leaked within 48 hours, while the negative control teeth remained uncontaminated throughout the test period. Leakage in the experimental teeth started at times varying from 10 to 71 days; 30% and 75% of the specimens of the Apexit and Tubliseal EWT groups respectively showed leakage at 90 days. The Tubliseal EWT group showed significantly more leakage (p < 0.05) than the Apexit group.


[Overview of reproductive toxicity studies on Tripterygium wilfordii in recent 40 years].
This paper summarizes the research progress of reproductive toxicity of Tripterygium wilfordii from 1979,and the toxicity characterization,damage mechanism,and attenuated measures are summarized. It was found that,the reproductive toxicity caused by T. wilfordii is mainly distributed on components of Tripterygium glycosides,triptolide,tripchlorolide,and clinically preparations,such as Leigongteng Tablets and Tripterygium Glycosides Tablets. Adverse reactions to male reproductive system caused by Tripterygium preparations mainly include decreased sperm motility,oligospermia or spermatozoa,decreased fertility or infertility,etc. Long-term drug use may also lead to testicular atrophy and decreased sexual desire. Adverse reactions to women are mainly manifested as menstrual disorders,decreased menstrual volume or even amenorrhea,decreased sexual desire,infertility,etc. The reproductive toxicity of T. wilfordii is related to apoptosis of reproductive cells,disturbance of spermatogenesis or oogenesis,damage of testis and ovary in reproductive target tissues,and changes of internal environment in gonad tissues( hormones,hormone synthesis rate-limiting enzymes and energy metabolism). Drug compatibility,hormone replacement,medication duration and dosage form changes can help reduce the damage of T. wilfordii to the reproductive system. In addition,in view of the existing problems in the current study,the author proposes new directions in clinical studies,pharmacological metabolism mechanism,preparation quality standards and new therapeutic effects,etc.,to provide a basis for the safe and reasonable clinical application of T. wilfordii.


Human papilloma virus in oral mucosa and its association with periodontal status of gynecologically infected women.
The aim of this study was to determine whether Human Papillomavirus was present in tongue and periodontium of periodontally healthy and diseased women who had genital lesions caused by the virus. Thirty non-menopausal women, systemically healthy and diagnosed with gynecological HPV lesions, were referred by the Gynecology Service Department of the University Maternal Neonatal Hospital of the City of Cordoba. Anamnesis, oral mucosa examination and periodontal clinical assessment were performed. Three brush samples were taken per patient: two from the same periodontal location (external epithelium of the gum and internal epithelium of the periodontal sulcus/pocket), and the third from the tongue. The 90 samples were submitted to Pap cytology and Polymerase Chain Reaction. The data were statistically analyzed by "Chi Square Test" (χ2) and "Kappa Index" (κ). High prevalence of HPV was found in the tongue (30%) and periodontal tissues (15%). High risk (HR) genotype -16 was detected with the highest percentage (67%), and genotypes -52 and -6 were also detected. Whenever HPV was present in periodontal location, it was also identified in the tongue of the same patients, of whom 88.89% reported that they practiced oral sex. Is worth noting the clinical finding of stomatologic lesions compatible with foliate papillitis in patients with positive intraoral HPV. High prevalence of HPV was found in the female population in Cordoba, with genotype -16 being detected at the highest percentage. No positive correlation was found between HPV and higher incidence and severity of periodontal lesions.


[Mullerian inhibiting substance type II receptor as a potential target for antineoplastic therapy].
The review considers properties of the type II anti-Mullerian hormone receptor (mullerian inhibiting substance receptor type II, MISRII), a transmembrane sensor with its own serine/threonine protein kinase activity, triggering apoptosis of the Mullerian ducts in mammalian embryogenesis and providing formation of the male type reproductive system. According to recent data, MISRII overexpression in the postnatal period is found in cells of a number of ovarian, mammary gland, and prostate tumors, and anti-Mullerian hormone (AMH) has a pro-apoptotic effect on MISRII-positive tumor cells. This fact makes MISRII a potential target for targeted anti-cancer therapy. Treatment based on targeting MISRII seems to be a much more effective alternative to the traditional one and will significantly reduce the drug dose. However, the mechanism of MISRII-AMH interaction is still poorly understood, so the development of new anticancer drugs is complicated. The review analyzes MISRII molecular structure and expression levels in various tissues and cell lines, as well as current understanding of the AMH binding mechanisms and data on the possibility of using MISRII as a target for the action of AMH-based antineoplastic drugs.


Terahertz magnetoplasmon-polaritons with nonlocal corrections for lossy two dimensional electron gas in GaN-based heterostructures.
The high electron concentration in GaN-based heterostructures necessitate the consideration of nonlocal corrections in the magnetoconductivity for the study of magnetoplasmon-polaritons (MPPs) in the lossy two dimensional electron gas system with grating couplers. With the complete set of Maxwell equations, the complex dispersion frequency and absorption spectrum are calculated numerically at different magnetic field (B max = 10 T) and plasmon wavevectors (k max = 5 × 107 m-1). Taking the AlGaN/GaN structure as a representative case, we observe the cyclotron resonance and its high order harmonics, as well as the MPP modes. The effective aspect ratio of the grating is determined according to the absorption spectrum. Effects of the nonlocal corrections on the dispersion frequency and absorption spectrum are analyzed in detail. The contributions of LO phonons, electron collisions, THz wave polarizations and retardations are also discussed.


Practical aspects of the application of helical tomotherapy for craniospinal irradiation.
We investigated the practical aspects of the application of craniospinal irradiation using helical tomotherapy (HT-CSI) by evaluating interfractional setup errors and intrafractional movement during each treatment in 83 patients undergoing HT-CSI between January 2014 and December 2018. Interfractional setup errors in each axis (mediolateral; ML, craniocaudal; CC, and anteroposterior; AP) were assessed as differences between pre-treatment megavoltage computed tomography (MVCT) images scanned (zygomatic arch to the C4 spine) and planning CT images. Intrafractional movements were evaluated as the difference between pre-treatment and post-treatment MVCT (T12-L4 spine) images at each fraction. Median interfractional setup error was acceptable in every axis (ML: 1.6 mm, CC: 1.9 mm, AP: 3.1 mm). Seven patients (8.4%) experienced significant intrafractional displacement from 1 to 10 fractions (0.34% for ML, 0.74% for CC, 1.21% for AP). Weight loss grade 1+ during treatment (p = 0.016) was an independent risk factor for significant intrafractional displacement. The risk factor for significant intrafractional movement in pediatric patients was weight loss grade 1+ (p = 0.020), while there was no factor in adults. HT-CSI could be a feasible treatment modality with acceptable setup verification. Inter- and intrafractional errors were acceptable; paying attention to weight loss during treatment is necessary, especially in pediatric patients.


Cytologic diagnosis of gastric cancer.
Follow-up of cytologic examinations of specimens obtained from 187 patients by gastric lavage with saline solution, without the use of enzymes or abrasive devices, showed a false positive rate of 0.6 per cent and a false negative rate of 17 per cent. To achieve satisfactory results with such examinations, great attention to detail in obtaining, preparing and examining the specimens is essential. Cytologic examination should be done in any case in which gastric cancer is suspected clinically or roentgenographic or gastroscopic findings arouse suspicion.


Application of ion chromatography to the determination of water-soluble inorganic and organic ions in atmospheric aerosols.
A simple, sensitive and convenient ion chromatography(IC) method was established for the simultaneous determination of twelve water-soluble inorganic anions(F- , Cl- , NO2(-), NO3(-), SO3(2-), SO4(2-) , PO4(3-)), and fifteen water-soluble organic ions(formate, acetate, MSA, oxalate, malonate, succinate, phthalates, etc.) in atmospheric aerosols. The linear concentrations ranged from 0.005 microg/m3 to 500 microg/m3 ( r = 0.999-0.9999). The relative standard deviation (RSD) were 0.43%-2.00% and the detection limits were from 2.7 ng/m3 to 88 ng/m3. The proposed method was successfully applied to the simultaneous determination of those inorganic ions and organic ions in PM2.5 of Beijing.


Influence of splenectomy on human acute tubular necrosis.
The incidence of acute tubular necrosis (need for hemodialysis immediately after transplantation) and its severity (the number of days dialysis was needed) were studied in 299 patients who were randomized prior to transplantation into undergoing splenectomy or not having splenectomy. There was no difference in the incidence of acute tubular necrosis between splenectomized and nonsplenectomized patients who received cadaveric grafts or kidneys from living related donors. In those patients in the cadaveric group who had acute tubular necrosis, the duration of need for dialysis was significantly less (p less than 0.05) in the splenectomized group (means = 8.9 days) when compared to the non-splenectomized group (means = 13.2 days). Animal experiments indicate that sustained prostaglandin release may be responsible for the decreased incidence and amelioration of acute tubular necrosis in splenectomized animals. Our study suggests that conclusions made in dogs about the influence of splenectomy on acute tubular necrosis may be applied to humans. Prostaglandin infusion may be a worthwhile method to abolish or ameliorate human acute tubular necrosis.


Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers.
Successful clinical methods for tumor elimination include a combination of surgical resection, radiotherapy, and chemotherapy. Radiotherapy is one of the crucial components of the cancer treatment regimens which allow to extend patient life expectancy. Current cutting-edge radiotherapy research is focused on the identification of methods that should increase cancer cell sensitivity to radiation and activate anti-cancer immunity mechanisms. Radiation treatment activates various cells of the tumor microenvironment (TME) and impacts tumor growth, angiogenesis, and anti-cancer immunity. Radiotherapy was shown to regulate signaling and anti-cancer functions of various TME immune and vasculature cell components, including tumor-associated macrophages, dendritic cells, endothelial cells, cancer-associated fibroblasts (CAFs), natural killers, and other T cell subsets. Dual effects of radiation, including metastasis-promoting effects and activation of oxidative stress, have been detected, suggesting that radiotherapy triggers heterogeneous targets. In this review, we critically discuss the activation of TME and angiogenesis during radiotherapy which is used to strengthen the effects of novel immunotherapy. Intracellular, genetic, and epigenetic mechanisms of signaling and clinical manipulations of immune responses and oxidative stress by radiotherapy are accented. Current findings indicate that radiotherapy should be considered as a supporting instrument for immunotherapy to limit the cancer-promoting effects of TME. To increase cancer-free survival rates, it is recommended to combine personalized radiation therapy methods with TME-targeting drugs, including immune checkpoint inhibitors.


Comparison of the pharmacological and biological properties of HPMA copolymer-pirarubicin conjugates: A single-chain copolymer conjugate and its biodegradable tandem-diblock copolymer conjugate.
In this study, we compared the enhanced permeability and retention (EPR) effect, toxicity, and therapeutic effect of the conjugate of the linear polymer poly(N-(2-hydroxypropyl)methacrylamide) (HPMA) with pirarubicin with an Mw below the renal threshold (39g/mol) (named LINEAR) and the disulfide-linked tandem-polymeric dimer of the poly(HPMA)-pirarubicin conjugate with an Mw above the renal threshold (93g/mol) (named DIBLOCK). The DIBLOCK conjugate, which was susceptible to reductive degradation, showed both a better EPR effect (tumor delivery) (2.5 times greater at 24h) and a prolonged plasma half-life. In addition, DIBLOCK had a better antitumor effect, as judged by percent survival, than did LINEAR (80% vs 65% at 150days), without any apparent toxicity in an S180 tumor model. However, the LD50 value of LINEAR was slightly higher than that of DIBLOCK (50mg/kg vs 37.5mg/kg, respectively). DIBLOCK required a longer time than LINEAR to reach maximum accumulation in the tumor. DIBLOCK also showed a greater time-dependent increase in the concentration in the tumor compared with the plasma concentration.


The Yes and No of the Ethylene Involvement in Abscission.
Abscission has significant implications in agriculture and several efforts have been addressed by researchers to understand its regulatory steps in both model and crop species. Among the main players in abscission, ethylene has exhibited some fascinating features, in that it was shown to be involved at different stages of abscission induction and, in some cases, with interesting roles also within the abscising organ at the very early stages of the process. This review summarizes the current knowledge about the role of ethylene both at the level of the abscission zone and within the shedding organ, pointing out the missing pieces of the very complicated puzzle of the abscission process in the different species.


Inequalities in self-rated health: explanations from different stages of life.
Inequalities in health are a major public-health concern. A greater understanding is needed on the relative importance of different causes. We investigated the contribution of risk factors identified at different life stages to inequalities in self-rated health. We used data from 5606 men and 5799 women in the 1958 British birth cohort followed-up to age 33 years, on health behaviour, education, adolescent health, family structure and social support, work characteristics, and material circumstances. We assessed the contribution of different factors to social-class differences in self-rated health by adjustment of odds ratios (classes IV and V vs I and II). Odds ratios of poor-rated health at age 33 were 3.15 for men and 2.30 for women, which decreased to 2.06 and 1.34, respectively, after adjustment for previously identified factors from birth to early adulthood. Adjustment for adult work characteristics, material circumstances, and health behaviour between ages 23 years and 33 years further decreased the odds ratios to 1.64 (men) and 1.11 (women). Most factors contributed to the reduction in odds ratios, although adolescent socioemotional adjustment, class at birth, educational qualifications, and psychosocial job strain were especially important. Additional key factors for men were adult smoking and job insecurity, and for women, housing during childhood, adult income, and age at first child. There was no single cause of health inequality at age 33 years. Explanations spanned from early life to young adulthood. Policy implications include reduction of social differences in material circumstances and of differences in individual skills and resources acquired in early life.


Functional analysis of the murine coronavirus genomic RNA packaging signal.
Coronaviruses selectively package genomic RNA into assembled virions, despite the great molar excess of subgenomic RNA species that is present in infected cells. The genomic packaging signal (PS) for the coronavirus mouse hepatitis virus (MHV) was originally identified as an element that conferred packaging capability to defective interfering RNAs. The MHV PS is an RNA structure that maps to the region of the replicase gene encoding the nonstructural protein 15 subunit of the viral replicase-transcriptase complex. To begin to understand the role and mechanism of action of the MHV PS in its native genomic locus, we constructed viral mutants in which this cis-acting element was altered, deleted, or transposed. Our results demonstrated that the PS is pivotal in the selection of viral genomic RNA for incorporation into virions. Mutants in which PS RNA secondary structure was disrupted or entirely ablated packaged large quantities of subgenomic RNAs, in addition to genomic RNA. Moreover, the PS retained its function when displaced to an ectopic site in the genome. Surprisingly, the PS was not essential for MHV viability, nor did its elimination have a severe effect on viral growth. However, the PS was found to provide a distinct selective advantage to MHV. Viruses containing the PS readily outcompeted their otherwise isogenic counterparts lacking the PS.


Plant invasion across space and time: factors affecting nonindigenous species success during four stages of invasion.
Invasive nonindigenous plant species (NIPS) threaten native diversity, alter ecosystem processes, and may interact with other components of global environmental change. Here, a general framework is outlined that attempts to connect patterns of plant invasion to processes underlying these patterns at four well-established spatio-temporal stages of the invasion process: transport, colonization, establishment, and landscape spread. At each stage we organize findings and ideas about the filters that limit NIPS success and the interaction of these filters with historical aspects of introduction events, NIPS traits, and ecosystem properties. While it remains difficult to draw conclusions about the risk of invasion across ecosystems, to delineate universal 'invader traits', or to predict large-scale extinctions following invasions, this review highlights the growing body of research that suggests that the success of invasive NIPS is controlled by a series of key processes or filters. These filters are common to all invasion events, and will interact throughout the stages of plant invasion, although the relative importance of a filter may be stage, species or location specific. It is suggested that both research and management programs may benefit from employing multiscale and stage approaches to studying and controlling invasion. We further use the framework to briefly examine potential interactions between climate change and filters that limit NIPS invasion.


Quality of transurethral resection of bladder tumor procedure influenced a phase III trial comparing the effect of KLH and mitomycin C.
Retrospective analysis of Center effect of the multi-center trial conducted to compare Immucothel (KLH Immunotherapy drug product) with Mytomycin-C (MM) concluded that efficacy evaluation of the drug product may be impacted by physician's subjective performance of Transurethral resection of bladder tumor (TURBT). A randomized trial was performed in 18 hospitals (clinical centers) and a total of 553 recruited, 283 patients under KLH arm and 270 patients under MM. An initial statistical analysis of efficacy comparisons between KLH and MM based on log-rank test performed for each center (hospital) showed 6 hospitals out of 18 hospitals a p-value of <0.05 and remaining 12 hospitals showed a p-values of >0.05. No association was observed between number of patients analysed and the associated p-values across hospitals. Final statistical analyses were carried out under each drug product using Kaplan-Meier survival analysis along with log-rank test after combining all eligible patients data for 6 hospital group and 12 hospital group. Median recurrence free survival (RFS) times (in weeks) showed statistical significance (p-value = 0.03) between two groups of hospitals under KLH arm, while similar median values showed no statistical significance (p-value = 0.05). Center effect with respect to median RFS values under KLH was more pronounced than under MM. Under the presence of such center effect, for reasons other than product related effects, concluding superiority of one drug product over another may create confounding bias conclusions in multi-center clinical trials. In the above cited clinical trial study, physician's prior experience on TURBT might have contributed to center effect in examining efficacies of KLH and MM. Similar observation was also noted in the literature on studies dealing with TURBT and in other clinical studies. Data set used in this study is based on previously documented clinical trial in the literature: See (Lammers et al., J Clin Oncol 30:2273-9, 2012) and Acknowledgments.


Application of MEN 203 as a polymorphic DNA probe in screening multiple endocrine neoplasia 2a.
Multiple endocrine neoplasia 2a (MEN 2a) is known to be genetically linked to a locus on chromosome 10. The application of polymorphic DNA probes for the region has made it possible to identify carriers of the disease susceptible gene. We performed DNA analysis for a newly found non-Caucasian MEN 2a family using MEN 203 as a probe. Data from DNA analysis of the family members were concordant with the results of conventional endocrinological tests. Furthermore, DNA analysis discriminated four individuals out of fifteen as non-carriers of the gene with a high degree of certainty. The results relieved these people from taking screening tests for years. DNA analysis employing suitable markers such as MEN 203 appears to be useful for a screening program of MEN 2a in Japanese as well as Caucasians.


The Shodair Medical Genetics Department--recent past and future developments.
Philip Pallister and John Opitz laid the ground work for a unique genetic service model in Montana that continues to flourish through ongoing support by the Montana Legislature, the Montana Department of Public Health and Human Services and the Shodair Foundation. At the heart of the model are clinical and laboratory genetic specialists based at Shodair Children's Hospital in Helena providing genetic care for patients through outreach clinics. Clinical services are supported by a state-of-the-art cytogenetics and molecular genetic laboratory as well a fetal genetic pathology program. Over the years, the reach of regular genetics clinics expanded to include large geographic areas including northwest (Kalispell), west central (Missoula), southwest (Bozeman, Butte), north central (Great Falls), and south central Montana (Billings). Building on the foundation of its world-renowned pioneers, the next generation of medical geneticists at Shodair carries the responsibility of integrating genomic medicine in the diagnosis and care of their patients, reducing inequality of services within Montana and partnering with colleagues across specialties to develop a more personalized practice of medicine.


Alveolar epithelial cells regulate the induction of endothelial cell apoptosis.
Mesenchymal cell apoptosis is important during development, tissue homeostasis, and repair. We sought to determine whether type II alveolar epithelial cells influence mesenchymal cell apoptosis, using the model of tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis of endothelial cells. Apoptosis was quantified by morphology and confirmed by electrophoretic DNA size analysis. Endothelial cells exposed to 20 ng/ml of TNF-alpha for 16 h exhibited apoptosis in 14.4 +/- 1.4% (SE) of the cells, whereas serum-free conditioned media (CM) from primary cultures of rat type II cells reduced TNF-alpha-induced apoptosis by 52% to 7.5 +/- 0.9% (P < 0.01). Flow cytometric analysis of subdiploid DNA content per cell also showed that CM reduced the percentage of cells with TNF-alpha-induced DNA degradation by 48 +/- 1.7%. The protective effect of CM was concentration dependent and also was effective across a range of TNF concentrations. This CM factor was trypsin sensitive and stable at 65 degrees C for 1 h. It bound to a Mono-Q anion-exchange resin, eluting in a discrete peak at 1.18 M NaCl and pH 8.5. Therefore alveolar type II cells release a heat-stable peptide(s) that protects endothelial cells against apoptosis induced by TNF. Our results suggest that alveolar epithelial cells regulate the response of mesenchymal cells to factors that induce apoptosis during injury and repair.


Formulation and Evaluation of Sol-Gel Drug Delivery System for Intracanal pH Sensitive Controlled Delivery of Chlorhexidine.
Persistence of viable micro-organisms even after thorough chemomechanical debridement has been cited as a major cause for endodontic failure. Chlorhexidine is a drug, which has shown marked efficacy against Enterococcus faecalis and Candida spp., which are mostly accounted for endodontic failure and it has demonstrated high degree of substantivity to dentin by adsorption. Another issue with chlorhexidine and other intracanal medicaments is the excessive or premature peaking of the drug leading to possible side effects. The objective of this experimental work undertaken was to formulate a pH sensitive sol-gel sustained drug delivery system containing chlorhexidine. The formulations were prepared using different concentrations of GELRITE® (0.1% and 0.2%) and Chlorhexidine (0.1% and 0.2%). The prepared solutions were evaluated for pharmacological properties like sterility test, viscosity, drug content, drug release characteristics, drug excipient compatible study. The drug excipient compatibility studies showed no interaction between the excipient and the active constituent. The microbial analysis showed good efficacy against the test micro-organisms and Minimum Inhibitory Concentration (MIC) values against Candida albicans (ATCC® 14053™) was observed as 4 μl/ml for both formulation containing 0.1% and 0.2% of GELRITE® Gellan (polymer). Whereas, MIC values against Enterococcus faecalis was observed to be 3.2 μl/ml and 6 μl/ml for formulation containing 0.1% and 0.2% of GELRITE® Gellan (polymer) respectively. From the present study, it could be successfully demonstrated that sol-gel formulations can be simple, easy to administer mode of intracanal drug delivery system. Localized pH changes present within the canal can trigger sol-gel conversion thereby releasing the drug in sustained manner with less toxicity and side effects.


Comparison of pathogenicity of various Candida albicans and C. stellatoidea strains.
In order to clarify the pathogenicity and the pathogenic factors of various Candida species strains, three strains, NIH A-207 and J-1012 (serotype A), and NIH B-792 (serotype B) of Candida albicans and two strains, ATCC 20408 (karyotype II) and ATCC 36232 (karyotype I) of C. stellatoidea, a synonym for C. albicans, were tested for their lethality to mice, adherence to Hela cells, hydrophobicity, and cell growth under acidic conditions, pH 2.0-5.9. The pathogenicity for mice of all the strains was observed in the order NIH B-792, ATCC 36232, J-1012, NIH A-207, and ATCC 20408. The pathogenicity for mice by all the strains used was well correlated with adherence to the Hela cells, the hydrophobicity, and the cell growth under the acidic condition, pH 2.0. These results emphasize that these specific properties of the C. albicans and C. stellatoidea strains play an important role in the pathogenesis of candidosis.


The current status of abortion laws in Latin America: prospects and strategies for change.
In order to explore ways of dealing with this phenomenon of illegal abortions and restrictive abortion laws in Latin America, several special sessions were held at last summer's international conference in Toronto, sponsored by the American Society of Law, Medicine & Ethics. The sessions brought together lawyers, health professionals, and reproductive rights advocates from a number of Latin American countries; their counterparts in the developed world; and representatives of non-governmental agencies concerned with this issue, including Catholics for a Free Choice. The goal of the sessions was to share information on the status of abortion in various countries and to try to devise strategies to make abortion law reform more palatable to Latin American governments and public opinion. One major component of the sessions was a series of papers prepared by some of the Latin American representatives describing and analyzing the situations in their countries. The papers illustrate some of the issues facing women in this part of the world.


Effects of Klotho on fibrosis and cancer: A renal focus on mechanisms and therapeutic strategies.
Klotho is a membrane-bound protein predominantly expressed in the kidney, where it acts as a permissive co-receptor for Fibroblast Growth Factor 23. In its shed form, Klotho exerts anti-fibrotic effects in several tissues. Klotho-deficient mice spontaneously develop fibrosis and Klotho deficiency exacerbates the disease progression in fibrotic animal models. Furthermore, Klotho overexpression or supplementation protects against fibrosis in various models of renal and cardiac fibrotic disease. These effects are mediated at least partially by the direct inhibitory effects of soluble Klotho on TGFβ1 signaling, Wnt signaling, and FGF2 signaling. Soluble Klotho, as present in the circulation, appears to be the primary mediator of anti-fibrotic effects. Similarly, through inhibition of the TGFβ1, Wnt, FGF2, and IGF1 signaling pathways, Klotho also inhibits tumorigenesis. The Klotho promoter gene is generally hypermethylated in cancer, and overexpression or supplementation of Klotho has been found to inhibit tumor growth in various animal models. This review focuses on the protective effects of soluble Klotho in inhibiting renal fibrosis and fibrosis in distant organs secondary to renal Klotho deficiency. We also discuss the structure-function relationships of Klotho domains and biological effects in the context of potential targeted treatment strategies.


Lumbee Native American ancestry and the incidence of aggressive histologic subtypes of endometrial cancer.
The Lumbee Indian tribe is the largest Native American tribe in North Carolina, with about 55,000 enrolled members who mostly reside in southeastern counties. We evaluated whether Lumbee heritage is associated with high-risk histologic subtypes of endometrial cancer. We retrospectively analyzed the available records from IRB-approved endometrial cancer databases at two institutions of patients of Lumbee descent (year of diagnosis range 1980-2014). Each Lumbee case was matched by age, year of diagnosis, and BMI to two non-Lumbee controls. Chi-square test was used to compare categorical associations. Kaplan-Meier methods and log-rank test were used to display and compare disease-free survival (DFS) and overall survival (OS). Multivariate Cox proportional hazards regression was used to adjust for age and BMI while testing cohort as a predictor of DFS and OS. Among 108 subjects, 10/35 (29%) Lumbee and 19/72 (26%) non-Lumbee subjects had high-risk (serous/clear cell/carcinosarcoma) histologic types (p = 0.8). 12/35 (34%) Lumbee and 24/72 (33%) non-Lumbee subjects had grade 3 tumors (p = 0.9). 5/33 (15%) Lumbee and 13/72 (18%) non-Lumbee had advanced stage endometrial cancer at diagnosis (p = 0.7). Lumbee ancestry was not associated with worse survival outcomes. OS (p = 0.054) and DFS (p = 0.01) were both worse in Blacks compared to Lumbee and White subjects. In this retrospective cohort analysis, Lumbee Native American ancestry was not a significant independent predictor of rates of high-risk histological subtypes of endometrial cancer or poor survival outcomes.


Positive association between plasma fibrinogen level and incident hypertension among men: population-based cohort study.
Elevated plasma fibrinogen is implicated in cardiovascular disease. However, it is not clear whether fibrinogen levels predict the development of hypertension. We examined the relationship between plasma fibrinogen level and hypertension in a population-based cohort study of 3654 participants (mean age: 61.5 years; range: 49 to 84 years) at the baseline examination (1992-1994) in the Blue Mountains region, west of Sydney, Australia, who were examined 5 years (1997-1999) later. Main outcomes of interest were prevalent hypertension (systolic blood pressure >or=140 mm Hg, diastolic blood pressure >or=90 mm Hg, or a combination of self-reported hypertension diagnosis and use of antihypertensive medications) at baseline (n=2212/3180) and 5-year incidence of hypertension among baseline normotensive individuals (n=361/637). Elevated plasma fibrinogen level was positively associated with prevalent hypertension both among men and women and positively associated with 5-year incident hypertension among men, independent of several cardiovascular risk factors. Multivariable odds ratio (95% CI) of 5-year incident hypertension comparing tertile 3 of plasma fibrinogen (>or=3.9 g/L) with tertile 1 (<or=3.2 g/L) was 1.95 (1.03 to 3.68; P trend=0.040). This prospective association, however, was not observed in women (odds ratio; 95% CI) comparing tertile 3 versus tertile 1 of plasma fibrinogen (1.00; 0.54 to 1.86; P trend=0.986). Subgroup analyses stratified by smoking, body mass index, diabetes, and blood pressure categories supported this male gender-specific pattern of association. These data provide prospective epidemiological evidence of an essential link between plasma fibrinogen level and incident hypertension among men but not among women, a finding consistent with that observed in the Atherosclerosis Risk in Communities Study.


Metabolism and function of phenazines in bacteria: impacts on the behavior of bacteria in the environment and biotechnological processes.
Phenazines constitute a large group of nitrogen-containing heterocyclic compounds produced by a diverse range of bacteria. Both natural and synthetic phenazine derivatives are studied due their impacts on bacterial interactions and biotechnological processes. Phenazines serve as electron shuttles to alternate terminal acceptors, modify cellular redox states, act as cell signals that regulate patterns of gene expression, contribute to biofilm formation and architecture, and enhance bacterial survival. Phenazines have diverse effects on eukaryotic hosts and host tissues, including the modification of multiple host cellular responses. In plants, phenazines also may influence growth and elicit induced systemic resistance. Here, we discuss emerging evidence that phenazines play multiple roles for the producing organism and contribute to their behavior and ecological fitness.


Patterns and Predictors of Use of Anticoagulants for the Treatment of Venous Thromboembolism Following Approval of Rivaroxaban.
Few studies have identified patterns and predictors of use of direct oral anticoagulants for venous thromboembolism (VTE). To describe the use of anticoagulants and assess predictors associated with the prescription of rivaroxaban over vitamin K antagonist (VKA) for the subsequent treatment of VTE. This cross-sectional study was built with all consecutive patients newly diagnosed with acute VTE admitted between February 18, 2013, and September 18, 2013, in an academic tertiary care center in Quebec, Canada. Patient characteristics and VTE treatments were described. Univariate analyses and a multiple forward stepwise logistic regression were performed to assess predictors of rivaroxaban use over VKA for the subsequent treatment of VTE. The study included 256 patients, 36.7% with a diagnosis of deep vein thrombosis (DVT) and 63.3% with pulmonary embolism (PE). Mean age was 63.1 years, and 28.1% of patients had cancer-associated VTE. Overall, rivaroxaban was prescribed in 1.6% of patients for the initial treatment and in nearly 20% of patients for the subsequent treatment of VTE. Low-molecular-weight heparin and VKA were mostly prescribed. Independent predictors associated with the prescription of rivaroxaban over VKA were as follows: age < 65 years (OR: 2.86, 95% CI 1.29-6.37), a diagnosis of DVT versus PE (OR 2.54, 95% CI 1.20-5.40), and an emergency department visit rather than a hospitalization (OR 2.24, 95% CI 1.06-4.71). Several months following its availability, rivaroxaban was rarely prescribed for acute VTE disease. It also appears to be prescribed in different patient populations than VKA.


The Critical Role of Infectious Disease in Compensatory Population Growth in Response to Culling.
Despite the ubiquity of disease in nature, the role that disease dynamics play in the compensatory growth response to harvesting has been ignored. We use a mathematical approach to show that harvesting can lead to compensatory growth due to a release from disease-induced mortality. Our findings imply that culling in systems that harbor virulent parasites can reduce disease prevalence and increase population density. Our models predict that this compensation occurs for a broad range of infectious disease characteristics unless the disease induces long-lasting immunity in hosts. Our key insight is that a population can be regulated at a similar density by disease or at reduced prevalence by a combination of culling and disease. We illustrate our predictions with a system-specific model representing wild boar tuberculosis infection, parameterized for central Spain, and find significant compensation to culling. Given that few wildlife diseases are likely to induce long-lived immunity, populations with virulent diseases may often be resilient to harvesting.


Induction of protective immunity against experimental Eimeria tenella infection using serum exosomes.
Avian coccidiosis is caused by Eimeria, a unicellular, apicomplexan protist which primarily infects intestinal epithelia resulting in nutrient malabsorption and reduced growth of commercial poultry. Vaccination of chickens with exosomes isolated from antigen presenting cells containing parasite antigens (Ags) represents a promising alternative strategy to control avian coccidiosis, but is restricted in its commercial application due to limitations on production scale-up for mass immunization programs. Here, we report the biochemical and physiologic characteristics of exosomes derived from serum of Eimeria tenella-infected chickens and their feasibility for inducing protective immunity to experimental coccidiosis. Exosomes isolated from the serum of E. tenella-infected chickens contained a subset of protein Ags found in the intact parasite. Serum-derived exosomes containing these E. tenella Ags localized to the intestine and spleen following intramuscular injection into naïve chickens. In vitro ELISPOT assays revealed increased numbers of IL-2-, IL-4-, IL-6-, and IFN-γ-secreting cells in the intestine and spleen of exosome-administered chickens, compared with vehicle controls. Pre-immunization of chickens with serum exosomes from E. tenella-infected chickens increased both body weight gain and feed conversion efficiency, and reduced both fecal parasite shedding and gut lesion scores following parasite infection, compared with vehicle controls. Finally, immunization with CD80(+) serum exosomes stimulated greater numbers of cytokine-producing cells, and higher levels of protective immunity to E. tenella infection, compared with CD80(-) exosomes. These results suggest the possibility of producing an effective, parasite-free vaccine against avian coccidiosis under field conditions using serum-derived CD80(+) exosomes containing parasite Ags.


Multidetector CT of the spine in multiple myeloma: comparison with MR imaging and radiography.
The purpose of this study was to compare multidetector CT (MDCT) of the thoracic and lumbar segments of the spine with MR imaging and conventional radiography for bone lesion detection and for evaluating the risk of vertebral fracture in multiple myeloma. Eighteen patients with multiple myeloma stage III (according to the criteria of Durie and Salmon) underwent MDCT, conventional radiography, and MR imaging of the lumbar and thoracic spine. MDCT was performed using a standard protocol with no contrast material. Source images were reconstructed using an effective slice thickness of 3 mm with an overlapping reconstruction increment (0.8 mm). Secondary coronal and sagittal multiplanar reformations were exclusively used for establishing the diagnosis. Findings were compared with those of MR imaging and conventional radiography. In all patients, coronal and sagittal multiplanar reformations depicted the extent of osseous destruction and provided detailed information about osseous infiltration and potential bone instability. Compared with conventional radiography, an additional 24 affected vertebrae, 15 additional vertebral fractures, and six vertebrae at further risk of fracture were detected on MDCT. Compared with MR imaging, three additional endangered vertebrae were detected on MDCT. MR imaging alone would have lead to an understaging of five (27.8%) of 18 patients. Using combined radiography and MR imaging, disease in three (16.7%) of 18 patients would have been understaged. MDCT seems to be preferable to conventional radiography in evaluating bone destruction in multiple myeloma. In combination with MR imaging, detailed information for staging these tumors is obtained. For the initial staging in patients with multiple myeloma, MDCT in combination with MR imaging seems to be the method of choice.


[Clinical, immunological and radioimmunological diagnosis of lung cancer detected in prophylactic fluorographic surveys].
A comprehensive survey, including clinical, X-ray, thermographic, immunological, and radioimmunological studies, was made in 56 patients with lung cancer detected on prophylactic fluorographic surveys and erroneously referred to the Lvov Regional Clinical and Diagnostic Phthisiopulmonological Center for suspected active pulmonary tuberculosis. Routine clinical and laboratory studies provided preliminary information in only 26.8% of cases and 73.2% needed additional examination by using currently available laboratory and instrumental studies. Of the most informative value for diagnosing malignancy is radioimmunocompetitive assay of serum levels of cancer embryonic antigen.


Calcium and the inner ear fluids.
Total calcium (Ca) concentration in inner ear fluids was determined by fluorimetry, emission and absorption spectrophotometry, and electron probe analysis. The ionized Ca was measured with selective microelectrodes. In perilymph, the total Ca concentration (1.2 mM) was similar to the ultrafiltrable Ca concentration in plasma. The fraction of ionized Ca was 80%. In endolymph, a total Ca concentration of 0.5 mM contrasted with a reported ionized Ca concentration of 0.02 mM, which suggests, as a working hypothesis, that most of the Ca could exist as bicarbonate and/or phosphate undissociated salts. The decrease in the endocochlear potential induced an increase of the ionized fraction of the Ca. The electrochemical potential of Ca across the perilymph-endolymph barrier implies an active entry of Ca into the endolymph.


Cross-Modal Correspondence Among Vision, Audition, and Touch in Natural Objects: An Investigation of the Perceptual Properties of Wood.
Certain systematic relationships are often assumed between information conveyed from multiple sensory modalities; for instance, a small figure and a high pitch may be perceived as more harmonious. This phenomenon, termed cross-modal correspondence, may result from correlations between multi-sensory signals learned in daily experience of the natural environment. If so, we would observe cross-modal correspondences not only in the perception of artificial stimuli but also in perception of natural objects. To test this hypothesis, we reanalyzed data collected previously in our laboratory examining perceptions of the material properties of wood using vision, audition, and touch. We compared participant evaluations of three perceptual properties (surface brightness, sharpness of sound, and smoothness) of the wood blocks obtained separately via vision, audition, and touch. Significant positive correlations were identified for all properties in the audition-touch comparison, and for two of the three properties regarding in the vision-touch comparison. By contrast, no properties exhibited significant positive correlations in the vision-audition comparison. These results suggest that we learn correlations between multi-sensory signals through experience; however, the strength of this statistical learning is apparently dependent on the particular combination of sensory modalities involved.


Asylum seekers, violence and health: a systematic review of research in high-income host countries.
We performed a systematic review of literature on violence and related health concerns among asylum seekers in high-income host countries. We extracted data from 23 peer-reviewed studies. Prevalence of torture, variably defined, was above 30% across all studies. Torture history in clinic populations correlated with hunger and posttraumatic stress disorder, although in small, nonrepresentative samples. One study observed that previous exposure to interpersonal violence interacted with longer immigration detention periods, resulting in higher depression scores. Limited evidence suggests that asylum seekers frequently experience violence and health problems, but large-scale studies are needed to inform policies and services for this vulnerable group often at the center of political debate.


Modified pectin-based carrier for gene delivery: cellular barriers in gene delivery course.
The use of polysaccharides as DNA carriers has high potential for gene therapy applications. Pectin is a structural plant polysaccharide heterogeneous with respect to its chemical structure. It contains branches rich in galactose residues which serve as potential ligands for membrane receptors interaction. In order to make the anionic pectin applicable for DNA complexation, it was modified with three different amine groups (cationic). Pectin-NH2 was prepared by modifying the galacturonic acids carboxyl groups with primary amine groups and further modified to generate pectin-T (T=N+H(CH3)(2)) and pectin-NH2-Q (Q=N+(CH3)(3)). All three modified pectins formed complexes with plasmid DNA as indicated by gel electrophoresis analysis. The size and morphology of pectin-NH2/DNA complexes were examined by transmission electron microscopy (TEM). Transfection experiments were carried out with human embryonic kidney cell lines (HEK293), using plasmid DNA encoding for green fluorescence protein (GFP). Transfection efficiency was analyzed by flow cytometry analysis, using FACS. Pectin-NH2-Q was the most efficient carrier. Addition of chloroquine ("lysosomotropic" agent) to transfection medium substantially enhanced the HEK293 transfection, indicating that endocytosis is the preferable internalization pathway and implies on the complex inability to escape the endosome. Pectin's galactose residues contribution to transfection was examined by inhibiting pectin binding to membrane receptors (galectins), using galactose and lactose as competitive inhibitors to this interaction. Resulting reduction of transfection efficiency demonstrated the importance of pectin's galactose residues to HEK293 transfection. Suggesting the modified pectin is a promising non-viral carrier for targeted gene delivery to cancer cells with galactose-binding lectins on their surface.


Prenatal lactation advice and intention to breastfeed: selected maternal characteristics.
This study uses data from the NICHD/MMIHS to examine the relationship among maternal characteristics and (a) whether mothers were asked by their prenatal providers to consider breastfeeding and (b) mothers' prenatal plans on how to feed their infants. Only 37% of the study population reported that their providers advised them to consider breastfeeding. Proportions of women who received prenatal advice to breastfeed and who intended to breastfeed were higher among married, Caucasian non-Hispanic, primiparous mothers, and women who were not enrolled in WIC. Women who received advice to breastfeed had significantly higher rates of planning to breastfeed (61.1%) than women who did not receive this advice (34.7%; p < 0.005). Efforts to meet the DHHS Healthy People 2000 objective for 75% of women to breastfeed in the early postpartum period will require a concentrated effort by prenatal providers to help women overcome their resistance to breastfeeding by offering support and encouragement.


Comparative prevalence of co-morbidities in smoking and non-smoking asthma patients with incomplete reversibility of airway obstruction, non-smoking asthma patients with complete reversibility of airway obstruction and COPD patients.
Asthma with incomplete reversibility of airway obstruction (IRAO) may often be associated to smoking-induced changes. Nevertheless, a high proportion of patients showing IRAO have never smoked. These patients with IRAO often share features of patients with chronic obstructive pulmonary disease (COPD). Although IRAO is still a poorly defined condition, it has been associated with a higher morbidity and mortality than asthma with complete reversibility of airway obstruction (CRAO) or even COPD alone. A high prevalence of comorbidities could contribute to the reported poorer clinical outcome in IRAO, in comparison to CRAO or COPD alone. To determine the prevalence of past and current comorbidities in IRAO patients compared to patients with CRAO or COPD. This was a retrospective, cross-sectional study. Demographic data, clinical characteristics and 36 predetermined comorbidities documented from self-report and chart review, were recorded from smoking-associated IRAO (S-IRAO), non-smoking IRAO (NS-IRAO), CRAO and COPD patients. A total of 199 patients were included in the final analysis (111F/88M, mean (±SD) age of 63 ± 10 years). The CRAO group had more comorbidities than the three other groups, but this difference was significant only with the NS-IRAO group (P = 0.04). For most comorbidities, the prevalence of comorbidities in both IRAO sub-groups was intermediate between CRAO and COPD, with significant differences between S-IRAO and NS-IRAO only for hypertension (P = 0.03), nasal polyps (P = 0.002) and pneumonia (P = 0.04). Typical asthma-associated comorbidities tended to be more prevalent in NS-IRAO patients and COPD-associated comorbidities in S-IRAO patients. In this study, the prevalence of comorbidities was not superior in patients with IRAO, compared to those with CRAO or COPD alone. The prevalence of comorbidities in the two main types of IRAO patients reflects exposure to cigarette smoke and asthma-related mechanisms.


DUSP 4 expression identifies a subset of colorectal cancer tumors that differ in MAPK activation, regardless of the genotype.
As dual-specificity phosphatase (DUSP) expression has been correlated to sensitivity to MEK inhibitors, DUSP expression levels may indicate activation of the mitogen-activated protein kinase (MAPK) pathway in many tumor types. In this study, we investigate if DUSP levels can indicate different levels of MAPK activation within colorectal cancer (CRC) patients. In three different CRC patient microarray datasets, we analyzed the expression of DUSP1. DUSP4 and DUSP6 according to mutational status, their correlation with survival and their association with different clinical characteristics. DUSP4 was significantly differentially expressed between all mutational subgroups with the highest expression in BRAF mutated tumors. Moreover, high DUSP4 expression was associated with a worse overall survival and with clinical characteristics typical for BRAF mutant patients. The use of DUSP expression as a predictive biomarker towards MAPK targeted therapy in CRC patients needs further investigation.


Bringing it all back home: Understanding the medical difficulties encountered by newly released prisoners in New Orleans, Louisiana - a qualitative study.
Formerly incarcerated persons (FIPs) face a disproportionate risk of death and serious illness in the immediate post-release period. Therefore, it is a critical time to initiate community-based care for chronic illnesses and behavioural disorders. Little is known about the unique transitional health and social support needs of FIPs in Louisiana, which has the highest incarceration rate in the world. As the average age of prisoners in the United States rises, the release of older prisoners with chronic conditions will become increasingly common. The aim of this study was to explore the healthcare experiences of FIPs in Louisiana in order to inform delivery of services tailored to this population. This research was done in partnership with a community organisation that advocates for restoration of voting rights to FIPs and helps newly released individuals transition back into society. This organisation identified FIPs in the Greater New Orleans area, and from January to May 2015, we conducted 24 semi-structured, in-person, audio-recorded interviews at the community organisation's transitional living facility. The interviews assessed FIPs' experiences with and barriers to receiving healthcare during and after incarceration. These discussions also explored FIPs' desires for services and attitudes towards health and healthcare. Interviews were transcribed and independently coded by two researchers. Interviewees reported negative experiences with healthcare during incarceration, and limited health guidance during the pre-release process. Post-release concerns included lack of insurance, difficulty accessing care and medication, and interest in learning about healthy lifestyles. Results suggest a need for a formalised system of transitional healthcare for FIPs. Findings are being used to inform a pilot transitional care clinic in New Orleans, Louisiana.


Pulsatile cerebrospinal fluid flow measurement using phase-contrast magnetic resonance imaging in patients with cervical myelopathy.
A technical report is presented. To investigate the relation between the severity of myelopathy and the degree of cerebrospinal fluid flow disturbance by using magnetic resonance imaging to measure the velocity of the cerebrospinal fluid flow in patients with cervical spondylotic myelopathy. Analyses of pulsatile cerebrospinal fluid flow measured by phase-contrast magnetic resonance imaging in healthy subjects and patients with Arnold-Chiari syndrome have been reported. Few studies have evaluated the change of pulsatile cerebrospinal fluid flow velocity and the waveform of the plotted velocity in patients with cervical spondylotic myelopathy. Study 1: Pulsatile cerebrospinal fluid flow was measured at C7, positioned with cervical spine flexion and extension, to investigate the influence of cervical alignment on the pulsatile cerebrospinal fluid flow in five patients with cervical spondylotic myelopathy. Study 2: In 31 patients with cervical spondylotic myelopathy, pulsatile cerebrospinal fluid flow was measured at C3 and C7, with the neck set centrally. The relevance of cerebrospinal fluid flow disturbance and the severity of myelopathy evaluated by the Japanese Orthopedic Association scoring system also were studied. Study 1: The waveform of plotted pulsatile cerebrospinal fluid flow velocity showed no change resulting from the position of the cervical spine. Study 2: A high correlation between the Japanese Orthopedic Association score and the cerebrospinal fluid pulsatile flow amplitude at C7 was demonstrated (r = 0.75; P < 0.0001). The average Japanese Orthopedic Association score of 14 patients whose cerebrospinal fluid flow velocity waveforms were absent was significantly lower (P < 0.0001) than that of 17 patients whose waveforms were present. The disturbance of pulsatile cerebrospinal fluid flow demonstrated high correlation with the severity of myelopathy. Measurement of cerebrospinal fluid flow disturbance can quantify the degree of dural sac and spinal cord compression.


Unsuspected second malignancy detection by FDG PET scan.
A whole body F-18 FDG PET scan was done on a 45-year-old man with a small cell carcinoma of the left lung for a metastatic survey. Imaging showed intense uptake in the left lung (maximum standardized uptake value (SUVmax) of 8.32 corrected for body weight), at the site of the primary and in the hilar lymph nodes. Focal intense uptake was also seen in the rectum (SUVmax of 21.73 corrected for body weight). No anatomic imaging for the pelvis was done, as the patient had no bowel symptoms. Posttreatment PET scan done 9 months after the first scan showed significant reduction in the primary mass in the lung (SUVmax 4.45) but an increase in the rectal mass (SUVmax 83.22). He now complained of bleeding per rectum. Colonoscopy and CT scan of the abdomen showed a mass in the rectum, which on biopsy revealed invasive adenocarcinoma.


Risk of colorectal cancer among immigrants to Ontario, Canada.
The risk of colorectal cancer (CRC) varies around the world and between females and males. We aimed to compare the risk of CRC among immigrants to Ontario, Canada, to its general population. We used an exposure-control matched design. We identified persons in the Immigration, Refugees and Citizenship Canada Permanent Resident Database with first eligibility for the Ontario Health Insurance Plan between July 1, 1991 and June 30, 2008 at age 40 years or older, and matched five controls by year of birth and sex on the immigrant's first eligibility date. We identified CRC from the Ontario Cancer Registry between the index date and December 31, 2014. All analyses were stratified by sex. We calculated crude and relative rates of CRC. We estimated risk of CRC over time by the Kaplan-Meier method and compared immigrants to controls in age and sex stratified strata using log-rank tests. We modeled the hazard of CRC using Cox proportional hazards regression, accounting for within-cluster correlation by a robust sandwich variance estimation approach, and assessed an interaction with time since eligibility. Among females, 1877 cases of CRC were observed among 209,843 immigrants, and 16,517 cases among 1,049,215 controls; the crude relative rate among female immigrants was 0.623. Among males, 1956 cases of CRC were observed among 191,792 immigrants and 18,329 cases among 958,960 controls; the crude relative rate among male immigrants was 0.582.. Comparing immigrants to controls in all age and sex stratified strata, the log rank test p < 0.0001 except for females aged > = 75 years at index, where p = 0.01. The age-adjusted hazard ratio (HR) for CRC among female immigrants was 0.63 (95% CI 0.59, 0.67) during the first 10 years, and 0.66 (95% CI 0.59, 0.74) thereafter. Among male immigrants the age-adjusted HR = 0.55 (95% CI 0.52, 0.59) during the first 10 years and increased to 0.63 (95% CI 0.57, 0.71) thereafter. The adjusted HR > = 1 only among immigrants born in Europe and Central Asia. The risk of CRC among immigrants to Ontario relative to controls varies by origin and over time since immigration.


Clinical Predictors of Recurrent Ventricular Arrhythmias in Secondary Prevention Implantable Cardioverter Defibrillator Recipients With Coronary Artery Disease - Lower Left Ventricular Ejection Fraction and Incomplete Revascularization.
The implantable cardioverter defibrillator (ICD) is a standard prevention therapy for patients at high risk for sudden cardiac death (SCD) due to life-threatening ventricular arrhythmia (VA), that is, ventricular fibrillation and ventricular tachycardia. However, clinical predictors of recurrent VA in secondary prevention ICD recipients with coronary artery disease (CAD) remain unknown. Methods and Results: We followed up 96 consecutive patients with CAD undergoing ICD implantation for secondary prevention of SCD. Long-term rates and clinical predictors of appropriate ICD therapy (ICD-Tx) for VA were analyzed. Appropriate ICD-Tx occurred in 41 (42.7%) patients during a median follow-up of 2.4 years (interquartile range, 0.9-6.1). These patients had significantly greater left ventricular end-diastolic diameter (62.3±1.3 vs. 54.6±1.1 mm, P<0.001), lower left ventricular ejection fraction (LVEF; 36.3±2.0% vs. 45.7±1.8%, P<0.001), and more incomplete revascularization (ICR; 70.7% vs. 45.5%, P=0.014) than those without appropriate ICD-Tx. Multivariable analysis showed that LVEF (hazards ratio [HR], 0.950; 95% CI: 0.925-0.975; P<0.001) and ICR (HR, 2.293; 95% CI: 1.133-4.637; P=0.021) were significant predictors of appropriate ICD-Tx for VA. Lower LVEF and ICR were independent predictors of recurrent VA in secondary prevention ICD recipients with CAD.


Bite mark impressions: a review of techniques and materials.
Many techniques are described in the literature for use in making impressions of bite mark indentations. A representative technique is presented in detail. Several types of dental materials common to many impression techniques are reviewed with regard to their accuracy, ease of use, and dimensional stability over time. Adherence of materials and a model pouring technique are also discussed.


Universal screening versus universal precautions in the context of preoperative screening for HIV, HBV, HCV in India.
In the Indian context, there is a convention of doing pre-operative screening for HIV, hepatitis B virus and hepatitis C viruses for all patients as a routine pre-intervention investigation. This approach is justified in some instances in the best interest of the patient. However, as routine screening is not the standard care internationally and as there is a significant divergence of views about the merits and demerits of this practice, this issue needs to be debated in a rational manner with an evidence-based approach. The present article is authored by a surgeon and a microbiologist from a new cancer care centre in eastern India, who has attempted to address this contentious issue. The various available options have been explored, and advantages and disadvantages of the different approach have been discussed. An algorithm for infection prevention and control has been presented so that surgeons and medical microbiologists could manage infection control challenges satisfactorily.


B7-H4 as a protective shield for pancreatic islet beta cells.
Auto- and alloreactive T cells are major culprits that damage β-cells in type 1 diabetes (T1D) and islet transplantation. Current immunosuppressive drugs can alleviate immune-mediated attacks on islets. T cell co-stimulation blockade has shown great promise in autoimmunity and transplantation as it solely targets activated T cells, and therefore avoids toxicity of current immunosuppressive drugs. An attractive approach is offered by the newly-identified negative T cell co-signaling molecule B7-H4 which is expressed in normal human islets, and its expression co-localizes with insulin. A concomitant decrease in B7-H4/insulin co-localization is observed in human type 1 diabetic islets. B7-H4 may play protective roles in the pancreatic islets, preserving their function and survival. In this review we outline the protective effect of B7-H4 in the contexts of T1D, islet cell transplantation, and potentially type 2 diabetes. Current evidence offers encouraging data regarding the role of B7-H4 in reversal of autoimmune diabetes and donor-specific islet allograft tolerance. Additionally, unique expression of B7-H4 may serve as a potential biomarker for the development of T1D. Future studies should continue to focus on the islet-specific effects of B7-H4 with emphasis on mechanistic pathways in order to promote B7-H4 as a potential therapy and cure for T1D.


Developing a donation after cardiac death risk index for adult and pediatric liver transplantation.
To identify objective predictive factors for donor after cardiac death (DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index (DCD-RI) to help in prospective decision making on organ use. The model included objective data from a single institute DCD database (2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated. DCD graft survival predictors were primary indication for transplant (P = 0.066), retransplantation (P = 0.176), MELD > 25 (P = 0.05), cold ischemia > 10 h (P = 0.292) and donor hepatectomy time > 60 min (P = 0.028). According to the calculated DCD-RI score three risk classes could be defined of low (DCD-RI < 1), standard (DCD-RI 2-4) and high risk (DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively. The DCD-RI score independently predicted graft loss (P < 0.001) and the DCD-RI class predicted graft survival (P < 0.001).