Rupture of a splenic artery aneurysm during pregnancy with maternal and foetal death: a case report.
Aneurysms of the splenic artery are rare although they are the most common of the so-called visceral artery aneurysms. First described by Beaussier in 1770, approximately 400 cases have now been reported in the literature. There is a strong association with pregnancy and since Corson's first description of the death of a mother in the third trimester from rupture of a splenic artery aneurysm, some 25% of reported cases have involved pregnant women. Arterial rupture is an obstetric emergency and associated with maternal and foetal mortality rates approaching 75% and 95% respectively. There are only 14 reported instances where both mother and baby survived. The clinical presentation is protean and in most cases splenic artery aneurysm is identified unexpectedly at angiography, laparotomy or post-mortem examination.


A Pilot Study: N-Staging Assessment of Shear Wave Elastrography in Small Cervical Lymph Nodes for Nasopharyngeal Carcinoma.
Purpose: To investigate N-staging Assessment of pretreatment Shear wave elastrography (SWE) in small cervical lymph nodes (0. 5 cm ≤ maximum diameter < 1 cm, intact capsule, no central necrosis, sCLNs) in nasopharyngeal carcinoma (NPC) patients. Methods: Pathological biopsy proven 28 NPC patients with sCLNs shown in pretreatment magnetic resonance (MR) images and 40 target lymph nodes were enrolled. All target lymph nodes were divided into metastasis and benign lymph node groups according to pathology. SWE was used to exam the real time SWE imaging of each target lymph nodes before conducting ultrasonography guided fine needle biopsy. The minimum (Emin), maximum (Emax), and mean (Emean) elasticity indices (kPa) of target lymph nodes were recorded. The SWE examination was repeated three times for the same target lymph node and each elasticity indices for statistic was determined by average of three measurements. SPSS 21.0 statistics software is used for statistical analysis. The receiver operating characteristic (ROC) curve was performed to obtain the cutoff value of elasticity indices of metastatic sCLNs. Statistical significance was assumed when the P < 0.05. Results: Nine lymph nodes were metastatic and 31 were benign. The Emin, Emax, and Emean of benign group were 8.15 ± 6.12, 25.05 ± 12.37, and 16.05 ± 8.29 kPa, respectively; Emin, Emax, and Emean of metastasis group were 11.5 ± 6.17, 41.38 ± 17.87, and 23.48 ± 6.50 kPa, respectively. The difference of the Emax and Emean between metastasis and benign group were statistically significant (P = 0.003 and 0.018). The area under the ROC curve of Emin, Emax, and Emean of metastasis lymph node were 0.685 (P = 0.095), 0.785 (P = 0.010), and 0.765 (P = 0.017), respectively. Emax of 27 kPa and Emean of 17 kPa were taken as the cutoff value of diagnosis for metastasis sCLNs: the sensitivity, specificity, and accuracy were 77.8 and 100%, 71.0 and 61.3%, 75.0 and 70.0%, respectively. Conclusions: Pretreatment SWE has high accuracy in evaluating the sCLNs in NPC patients and is helpful for accurate N-staging and survival prognosis. It can be used as a clinical supplementary examination.


Role of a novel benzoxazine derivative in the chemosensitization of colon cancer.
The concept to fight against tumour resistance is to use chemosensitizers that selectively sensitize tumour cells to chemotherapeutic drugs without affecting normal tissue. In this study, the chemosensitizing potential of a novel benzoxazine derivative in combination with Doxorubicin, a DNA damaging chemotherapeutic drug was evaluated. The results of this study showed that the compound LTUR6 is a potent chemosensitizer of Doxorubicin in colon cancer cell lines, HCT116 and HT29. It was also observed that LTUR6 delayed the resolution of Doxorubicin-induced γH2AX, a specific marker of unrepaired DNA DSB, and prolonged cell cycle arrest in both cell lines. This eventually led to DNA fragmentation, caspase activation and ultimately apoptosis in LTUR6 treated cell lines. Results of western blot analysis revealed that LTUR6 significantly inhibited the phosphorylation of DSB repair enzyme AKT, in response to Doxorubicin-induced DSB. We propose that the chemosensitization observed following inhibition of PI3K is likely due to the involvement of a number of downstream targets of AKT.


Personalized Therapy of Chronic Hepatitis C and B Dually Infected Patients With Pegylated Interferon Plus Ribavirin: A Randomized Study.
We aimed to investigate whether response-guided therapy (RGT) with peginterferon-alpha plus ribavirin by using hepatitis C virus (HCV) genotype, pretreatment HCV RNA levels, and rapid virological response (RVR, undetectable HCV RNA at treatment week 4) could be applied for active HCV/hepatitis B virus (HBV) dually infected patients, without compromised the treatment efficacy.A total of 203 patients, seropositive of HCV antibody, HCV RNA and HBV surface antigen (HBsAg), and seronegative for HBV e antigen for >6 months, were randomized to receive peginterferon-alpha/ribavirin by either genotype-guided therapy (GGT, n = 102: HCV genotype 1 [HCV-1], 48 weeks; HCV-2/3, 24 weeks) or RGT (n = 101: HCV-1, 48 or 24 weeks if patients with baseline VL <400,000 IU/mL and RVR; HCV-2/3, 24 or 16 weeks if patients with RVR). The primary endpoint was HCV-sustained virological response (SVR).The HCV SVR rate was comparable between the GGT (77.5%, 79/102) and RGT groups (70.3%, 71/101, P = 0.267), either among HCV-1/HBV (69.4% [43/62] vs 63.5% [40/63], P = 0.571) or among HCV-2/3/HBV (90.0% [36/40] vs 81.6% [31/38], P = 0.342) dually infected patients based on intention-to-treat analysis. In HCV-1/HBV dually infected patients, RVR (odds ratio [OR]: 6.05; 95% confidence intervals [CI]: 2.148-17.025, P = 0.001) and lower pretreatment blood glucose levels (OR: 0.97; CI: 0.944-0.989, P = 0.003) were independent predictors of HCV SVR. Although RVR (OR: 10.68; CI: 1.948-58.514, P = 0.006) was the only significant factor associated with HCV SVR in HCV-2/3/HBV dually infected patients. HBsAg loss at 1 year posttreatment was observed in 17 of 185 (9.2%) patients. The rates of discontinuation and adverse events were similar between the 2 groups.RGT with peginterferon-alpha/RBV may be considered for HBeAg-negative HBV/HCV dually infected patients.


Hypogonadotropic disorders in men and women: diagnosis and therapy with pulsatile gonadotropin-releasing hormone.
Hypogonadotropic hypogonadism (HH) is a clinical syndrome occurring in both sexes which has long puzzled clinicians due to the apparent paradox of nonfunctioning gonads in the face of normal or only slightly lowered levels of circulating gonadotropins. Using frequent sampling of gonadotropin levels as an index of hypothalamic GnRH secretion, we have examined the hypothesis that this group of disorders represents a spectrum of abnormal patterns of the pulsatile release of endogenous GnRH. After a broad, normative data base was established in both men and women for purposes of comparison, it appears that quantifiable abnormalities of GnRH secretion are discernible in both males and females with HH. These abnormalities include a total absence of GnRH secretion, defects of the amplitude and frequency of its secretion, and altered bioactivity of the gonadotropins released. In addition, physiological regimens of hypothalamic replacement therapy with exogenous GnRH, which are fashioned to mimic the normal frequency of endogenous GnRH secretion, result in complete normalization of reproductive function and fertility in hypogonadotropic subjects of both sexes. Thus, the heterogeneous nature of HH, as well as its favorable clinical and biochemical responses to GnRH, suggest that the basic defect in this family of disorders involves a partial or complete inability to synthesize and/or release GnRH from the hypothalamus in a manner compatible with physiological reproductive function. Conversely, these findings imply that maintenance of a physiological amplitude and frequency of endogenous GnRH secretion appear to be essential for normal reproductive function.


Determination of methyl 2-benzimidazolecarbamate in bulk fruit juice concentrates by competitive-inhibition enzyme immunoassay.
A polyclonal enzyme immunoassay (EIA) was used to quantitate methyl 2-benzimidazolecarbamate (MBC or carbendazim), a degradation product of benomyl, in bulk fruit juice concentrates. These concentrates are used by industrial producers to prepare juice or juice concentrates sold in supermarkets. Total sample analysis time was less than 18 min without cleanup or 35 min with cleanup. As many as 8 samples can be analyzed simultaneously, with a limit of quantitation of 10 ppb. The assay's dynamic range ran from 0.5 to 20 ppb MBC but was best from 0.5 to 10 ppb. Intra-assay coefficients of variation (CVs) varied from 4.0 to 13% for standards and from 4.1 to 26% for samples. Interassay CVs varied from 4.5 to 47% for standards and 5.6 to 22% for samples. Average recovery of several juice concentrates spiked at 10 to 290 ppb was 97%. A total of 140 juice concentrates comprising 20 different kinds of juice were analyzed by 2 EIA methods and one liquid chromatographic (LC) procedure. MBC-positive samples gave the following correlation coefficients: 0.954 for EIA without cleanup vs LC, 0.956 for EIA with cleanup vs LC, and 0.978 for EIA with cleanup vs EIA without cleanup. MBC concentrations in MBC-positive juice samples ranged from 5 to 2960 ppb.


The mechanism of the phosphine-free palladium-catalyzed hydroarylation of alkynes.
The mechanism of the Pd-catalyzed hydroarylation and hydrovinylation reaction of alkynes has been studied by a combination of experimental and theoretical methods (B3LYP), with an emphasis on the phosphine-free version. The regioselectivity of the hydroarylation and hydrovinylation shows unexpected differences, which could be attributed mainly to the higher steric demand of the cyclohexenyl group as compared to the phenyl group. Hydroarylation of alpha,beta-acetylenic carbonyl substrates yields a very unusual anti-Michael selectivity, which is shown to result from reaction of the nonconjugated double bond, leaving the conjugation intact. In all cases were the regioselectivities reproduced by the calculations.


CC Chemokine Ligand 20 and Its Cognate Receptor CCR6 in Mucosal T Cell Immunology and Inflammatory Bowel Disease: Odd Couple or Axis of Evil?
Chemokines and their cognate receptors have been identified as major factors initiating and governing cell movement and interaction. These ligands and their receptors are expressed on a wide variety of cells and act during steady-state migration as well as inflammatory recruitment. CCR6 is a non-promiscuous chemokine receptor that has only one known chemokine ligand, CCL20, and is present on B and T cells as well as dendritic cells (DCs). Two CD4(+) T cell populations with opposing functions present in the intestines and the mesenteric lymph nodes express CCR6: the pro-inflammatory TH17 and regulatory Treg cells. CCL20 is also present in the intestine and is strongly up-regulated after an inflammatory stimulus. Interestingly, this ligand is also expressed by TH17 cells, which opens up the possibility of autocrine/paracrine signaling and, consequently, a self-perpetuating cycle of recruitment, thereby promoting inflammation. Recently, CCR6 has been implicated in inflammatory bowel disease (IBD) by genome wide association studies which showed an association between SNPs in the genomic region of the CCR6 gene and the inflammation. Furthermore, recent research targeting the biological function of CCR6 indicates a significant role for this chemokine receptor in the development of chronic IBD. It is therefore possible that IBD is facilitated by a disordered regulation of TH17 and Treg cells due to a disruption in the CCL20-CCR6 axis and consequently disturbed mucosal homeostasis. This review will summarize the literature on CCL20-CCR6 in mucosal immunology and will analyze the role this receptor-ligand axis has in chronic IBD.


Nutrition intervention for weight gain in cystic fibrosis: a meta analysis.
A meta analysis of the literature on treatment approaches to malnutrition in cystic fibrosis (CF) was conducted to evaluate the effectiveness of oral supplementation, enteral nutrition, parenteral nutrition, and behavioral intervention on weight gain before and after treatment. Eighteen studies were reviewed: four behavioral, six supplement, five enteral nutrition, and three parenteral nutrition. The weighted effect size for weight gain was large for each intervention: 1.51 behavioral, 1.62 oral, 1.78 enteral, and 2.20 parenteral intervention. All interventions produced a large effect for weight gain in patients with CF. A univariate analysis of variance indicated no significant difference among the four interventions, F(3, 17) = 0.87, p > 0.05. Effect size for calorie intake was also evaluated when data were available (N = 7 studies), yielding a sample size of three behavioral, two enteral, and two oral supplement studies. Analysis of variance indicated a significant effect for treatment, F(2,4) = 13.34, p < 0.05, with post hoc analysis indicating that the behavioral intervention had a greater effect size for calorie intake than oral supplement. All interventions were effective in producing weight gain in patients with CF. Behavioral intervention appeared to be as effective in improving weight gain in patients with CF as more invasive medical procedures. These findings support continued research on nutrition intervention with patients with CF including controlled clinical trials of the interventions and long-term follow-up on the impact of nutrition on disease progression.


Rapid spread of a novel NDM-producing clone of Klebsiella pneumoniae CC147, Northern Italy, February to August 2023.
New Delhi metallo-beta-lactamase (NDM)-producing Klebsiella pneumoniae (Kp) ST147 caused a large multi-hospital outbreak in Italy from 2018 to 2021. We describe a new ST6668 NDM-producing Kp clone, belonging to CC147, which rapidly spread across hospitals in the Pavia province (Northern Italy) from February to August 2023. Genomic analyses revealed that ST6668 is different from ST147 and fast evolving. As shown here, genomic surveillance programmes are useful for tracking the spread of new clones with reduced susceptibility to most antibiotics.


Local increase in hyaluronic acid and interleukin-2 in the capsules surrounding silicone breast implants.
Connective tissue disease-like illness has been associated with silicone breast implants. However, no data are currently available on the immunopathology of the capsule surrounding the breast implants. Sera from women with breast implants were collected and assayed for interleukin-6 (IL-6), IL-2, and hyaluronic acid. Capsular biopsies were stained with a probe for HYA or with monoclonal antibodies specific for human macrophages (CD68), T cells (CD4), IL-6, and IL-2. Control specimens consisted of breast biopsies from women undergoing reduction mammoplasty. Our results revealed an increased local amount of hyaluronic acid in the capsule of patients with breast implants compared with control breast tissue. The HYA was localized extracellularly in areas containing fibrosis and cellular infiltrates. The infiltrating cells were determined to be primarily macrophages and T cells. No IL-6 was localized in any of the tissue sections. In contrast, large amounts of IL-2 were found in regions of infiltrating lymphocytes. No significant increase in IL-6, IL-2, or hyaluronic acid was found in the sera. The role of hyaluronic acid and cytokines in the inflammatory response in the capsules of silicone breast implants is discussed.


Multi-omics profiling: the way towards precision medicine in metabolic diseases.
Metabolic diseases including type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome (MetS) are alarming health burdens around the world, while therapies for these diseases are far from satisfying as their etiologies are not completely clear yet. T2DM, NAFLD, and MetS are all complex and multifactorial metabolic disorders based on the interactions between genetics and environment. Omics studies such as genetics, transcriptomics, epigenetics, proteomics, and metabolomics are all promising approaches in accurately characterizing these diseases. And the most effective treatments for individuals can be achieved via omics pathways, which is the theme of precision medicine. In this review, we summarized the multi-omics studies of T2DM, NAFLD, and MetS in recent years, provided a theoretical basis for their pathogenesis and the effective prevention and treatment, and highlighted the biomarkers and future strategies for precision medicine.


Surgical management of an odontogenic cutaneous fistula.
A patient presented to our unit with a long history of a discharging skin infection on his left cheek, which came and went. He had been seen by numerous healthcare practitioners including his general practitioner, general dental practitioner and dermatologist, with no resolution. He was eventually diagnosed with an odontogenic cutaneous fistula (OCF), for which he underwent surgical management. The purpose of the study is to describe the diagnosis and surgical management of an OCF, from initial assessment through to postoperative review and discharge. Following surgical management of the OCF and treatment of the source of infection by dental extraction, the patient is no longer experiencing purulent discharge through his left cheek. The extraoral skin site of drainage at his left cheek has resolved completely, with minimal residual scarring. OCF can be managed by a number of different treatment modalities. The treatment of an OCF by surgical excision is presented.


Volatile anesthetic isoflurane exposure facilitates Enterococcus biofilm infection.
Enterococcus faecalis (E. faecalis) is one of the major pathogenic bacteria responsible for surgical site infections. Biofilm infections are major hospital-acquired infections. Previous studies suggested that ions could regulate biofilm formation in microbes. Volatile anesthetics, frequently administered in surgical setting, target ion channels. Here, we investigated the role of ion channels/transporters and volatile anesthetics in the biofilm formation by E. faecalis MMH594 strain and its ion transporter mutants. We found that a chloride transporter mutant significantly reduced biofilm formation compared to the parental strain. Downregulation of teichoic acid biosynthesis in the chloride transporter mutant impaired biofilm matrix formation and cellular adhesion, leading to mitigated biofilm formation. Among anesthetics, isoflurane exposure enhanced biofilm formation in vitro and in vivo. The upregulation of de novo purine biosynthesis pathway by isoflurane exposure potentially enhanced biofilm formation, an essential process for DNA, RNA, and ATP synthesis. We also demonstrated that isoflurane exposure to E. faecalis increased cyclic-di-AMP and extracellular DNA production, consistent with the increased purine biosynthesis. We further showed that isoflurane enhanced the enzymatic activity of phosphoribosyl pyrophosphate synthetase (PRPP-S). With the hypothesis that isoflurane directly bound to PRPP-S, we predicted isoflurane binding site on it using rigid docking. Our study provides a better understanding of the underlying mechanisms of E. faecalis biofilm formation and highlights the potential impact of an ion transporter and volatile anesthetic on this process. These findings may lead to the development of novel strategies for preventing E. faecalis biofilm formation and improving patient outcomes in clinical settings.


Appendiceal Perforation due to Migration of a Dental Instrument.
A 40-year-old male without any past medical history accidentally swallowed a titanium dental instrument (reamer) for root canal treatment. A cathartic was prescribed at a local hospital, and the course was observed. However, since the reamer was not excreted in feces, he was referred to our hospital. After admission, CT, lower gastrointestinal endoscopy, and barium enema revealed the migration of a foreign body into the appendix and its protrusion into the intraperitoneal cavity. As an emergency operation, laparoscopic appendectomy including the foreign body was performed. The following course was favorable without postoperative complications, and he was discharged on the 2nd hospital day. We report a patient with appendiceal perforation due to a foreign body (dental instrument for root canal treatment) in the appendix.


Three Effective, Efficient, and Easily Implementable Ways to Integrate A.I. Into Medical Education.
As a medical school CEO who is following the development of A.I. very closely, I believe that med students are eager to adopt the possibilities that A.I. tools can deliver in their training. Not only do these students already use variations of A.I. in other areas of their lives, but they also embrace advanced technology and understand how to use it. With the tech readiness of today's students in mind, I have devised three recommendations for how to best infuse A.I. into medical education. This strategic guidance can deliver significant benefits to today's tech-fluent medical school students and enhance their training in their journeys to become doctors.


[Hemodynamic correction of patients with acute myocardial infarct in hemodynamic subgroup III by plasma-exchange expansion with low-molecular dextran].
To 20 patients with acute myocardial infarction from the III hemodynamic group catheterized with a microcatheter or a balloon thermodilution catheter 332 (from 100 up to 500) ml of a 10% solution dextran 40 were infused intravenously with mean velocity of 33 ml/min. The cardiac index was measured by the dye or thermodilution methods. The left ventricular filling pressure (LVFP) increased with 47% (from 1.7 +/- 0.4 to 2.5 +/- 0.5 kPa), the cardiac index--15.8% (from 2.02 +/- 0.8 to to 2.34 +/- 0.37 l/min/m2), systolic and diastolic arterial pressure with 7.7%, stroke index--with 10.2% stroke working index--with 10.7%, total pulmonary resistance--with 37.9% (il all, p less than 0.001), cardiac rate--with 4.7% (p less than 0.05) but the systemic arterial resistance did not change (p greater than 0.10). The increase of the cardiac index for an increase of LVFP with I KPa was almost equal in the patients with different initial LVFP but was due mainly to the increase of the stroke index by LVFP below 1.3 kPa and to an increase of the heart rate by LVFP above 2.0 kPa. The cardiac index increased above 2.2 l/min/m2 in 45% of the patients (87% by LVFP below 1.3 kPa, 56% by LVFP 1.4-1.9 kPa and 0% by LVFP above 2 kPa). The cardiac rate remained increased up to the 4th hour after the infusion. The arterial pressure fell below its initial value after 30 min and remained low up to the 12 h. The LVFP decreased progressively according to the dependence: LVFP = -5.06 + 2.09 1g T.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of novel Sjogren's syndrome autoantibodies in patients with dry eyes.
Dry eye is a common problem in Ophthalmology and may occur for many reasons including Sjogren's syndrome (SS). Recent studies have identified autoantibodies, anti-salivary gland protein 1 (SP1), anti-carbonic anhydrase 6 (CA6) and anti-parotid secretory protein (PSP), which occur early in the course of SS. The current studies were designed to evaluate how many patients with idiopathic dry eye and no evidence of systemic diseases from a dry eye practice have these autoantibodies. Patients from a dry eye clinic and normal controls were assessed by Schirmer's test for tear flow. Sera were assessed for autoantibodies using ELISA assays. Statistics was performed with Prism 7 software and student's unpaired t test. In this study 60% of the dry eye patients expressed one of these autoantibodies. Only 30% expressed one of the autoantibodies associated with long-standing SS, which are included in the diagnostic criteria for SS, anti-Ro and anti-La. Patients with disease for less than 2 years and mild dry eyes did not express anti-Ro or anti-La, while 25% expressed anti-SP1. Similar observations, with smaller numbers, were made when patients had not only dry eye but also dry mouth. Antibodies to SP1, CA6 and PSP occur in some patients with idiopathic dry eyes. Further studies will be needed to determine how many of these patients go on to develop systemic manifestations of SS. Testing for these autoantibodies may allow early recognition of patients with SS. This will lead to improved management of the patients and the development of new strategies to maintain normal lacrimal and salivary gland function in patients with SS.


CRISPR-Cpf1: A New Tool for Plant Genome Editing.
Clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated proteins (CRISPR-Cas), a groundbreaking genome-engineering tool, has facilitated targeted trait improvement in plants. Recently, CRISPR-CRISPR from Prevotella and Francisella 1 (Cpf1) has emerged as a new tool for efficient genome editing, including DNA-free editing in plants, with higher efficiency, specificity, and potentially wider applications than CRISPR-Cas9.


The regulatory effect of estrogens on fetal growth. IV. Brain development in growth accelerated fetuses in rabbits.
Brain weights and DNA, RNA, and total protein concentrations were determined on 31-day-old fetuses whose growth had been accelerated incidental to estrogen deficiency following maternal oophorectomy. Compared to controls, there were no differences in the DNA, RNA, or total protein concentrations, although the mean brain weight was increased. The higher mean brain weight in the growth accelerated fetuses was related to the increased mean fetal weight, and did not represent an independent response to the estrogen deficiency. A comparison of the influence of fetal weight versus gestational age on the weight of the fetal brain shows that gestational age exerts an effect apart from that of fetal weight.


Prisoner of war experience: effects on wives.
The aim of this study was to compare the wives of Australian soldiers who had been imprisoned during World War II (POWs) with a control group of non-POWs' wives and also to compare the POWs and non-POWs themselves in respect to several psychological and family life characteristics on which differences might be expected to arise from the long-term effects of imprisonment. A random sample of 145 of these veterans and their wives completed several self-administered mood and family life scales, an inventory of somatic symptoms, questions about the impact of the war on the veteran in the postwar decades, and several social background questions. The POWs themselves were more depressed and reported more somatic symptoms and a greater postwar impact of the war than the non-POWs. However, these differences were not accompanied by concomitant differences among their wives. There was some evidence of an influence of the POW's mood on his wife's mood in significant correlations between husbands' and wives' depression and anxiety scale scores in POW couples alone. Otherwise, there was very little indication that the POW experience had any long-term effect on the marriage relationship as measured by the variables included in this study.


Characteristics of gait in hemiplegia.
The following review examines the walking patterns of patients who have hemiplegia, primarily as a result of a stroke. Attention is given to the changes in the distance and temporal factors of walking, phasic patterns and joint ranges of motion throughout the walking cycle, the ground reaction forces, joint moments of force, joint powers, energy expenditure, and muscle activation patterns. The effect of orthotic intervention on these walking parameters is also addressed. A frequently cited issue regarding the gait patterns of these patients was that their walking patterns exhibit significant deviations from normal healthy individuals. Although hemiplegia is primarily associated with unilateral motor involvement, changes in almost all of the parameters used to assess walking were evident on both the involved and uninvolved sides of the body. Last, although hemiplegia appears to reflect a single diagnostic category, there is large interindividual variability in the patterns of gait deviations, which suggests that the management and treatment of these patients need to address the unique deficits of the individual.


[Mechanism of innate immunity and adaptive immunity in the development of allergic rhinitis].
The pathogenesis of allergic rhinitis (AR) has not well been clarified, and the imbalance of immune system is its important feature. Interaction between innate and adaptive immune cells and inflammatory mediators secreted by them triggers, maintains and aggravates AR. In this review, Toll-like receptor signaling pathways are used as a bridge to systematically analyze the mechanisms of innate and adaptive immunity in the development of AR.


The pathway between hyaloid blood and retinal neurons in the toad. Structural observations and permeability to tracer substances.
The hyaloid vessels form a capillary network on the inner surface of the retina. These capillaries are embedded in the vitreous humor, and they lack a glial investment. The intercellular spaces of the retina communicate with the ocular cavity, as can be evidenced by following the penetration of tracer substances. Hence, there is an extracellular diffusion pathway between hyaloid capillaries and retinal neurons, without interposition of glial cells. Trypan blue and ferrocyanide were not detected within the vitreous humor nor the retina after systemic injection. To this extent, at least, the hyaloid capillaries functionally resemble central nervous system capillaries. Intravascular injections of horseradish peroxidase established the absence of vesicular transfer across the endothelium of the hyaloid capillaries. In addition, quintuple-layered junctions between endothelial cells prevented the intercellular passage of the enzyme. It is likely, therefore, that the only pathway across the endothelium of the hyaloid capillaries is through the plasmalemma of the endothelial cells.


Pilot test for linking population-based cancer registries with CCG/POG pediatric registries.
An estimated 8,600 new cases of cancer are expected to be diagnosed in children aged 0-14 in the United States during 2001. Childhood cancer rates vary considerably by age with rates of 20.1 cases/100,000 for ages 0-4, 10.8 cases/100,000 for ages 5-9, 12.0 cases/100,000 for ages 10-14, and 19.6 cases/100,000 for ages 15-19. While the overall cancer mortality rate among children aged 0-14 declined by an average 2.9% per year during the time period 1975-1998, the overall incident rate, as measured by the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) Program, increased by an average 0.8% per year. Concern over the increasing incidence rate has led to increasing public demands for research on the causes of childhood cancer and for research on patterns of care among children and adolescents with cancer. Several groups have proposed that a national childhood cancer registry would enhance research opportunities. The NCI is proceeding to develop a National Network for Research on Cancer in Children which among other components would include merging databases of the NCI's Childhood Cancer Group (CCG) and the Pediatric Oncology Group (POG) to create a National Childhood Cancer Registry (NCCR). However, several studies have documented that the CCG and POG do not enroll all children with cancer in the US, and that they enroll even fewer adolescents. A recent tabulation of the California Cancer Registry (CCR) database for cases diagnosed in 1996 showed that 74.6% of childhood cancer cases among ages 0-14 were reported to the CCR by CCG/POG facilities but only 37.2% of cases among ages 15-19 were reported by those same facilities. Therefore, it is well recognized that the NCCR will need to collaborate with state and SEER population-based cancer registries in order to obtain complete case ascertainment. Similarly, the Centers for Disease Control and Prevention (CDC) National Program of Cancer Registries (NPCR) has been investigating methods for states to: (1) efficiently collect incident cancer case reports including childhood and adolescent cancers, (2) validate completeness of state case ascertainment, and (3) increase the research potential for NPCR-collected data.


Distally based superficial sural fasciomusculocutaneous flap: a reliable solution for distal lower extremity reconstruction.
The objective of this study is to present a simple and rapid approach to elevate a consistent superficial sural fasciomusculocutaneous flap and show its clinical applications. All the patients with lower limb defects who underwent reconstruction using the distally based fasciomusculocutaneous sural flap were included in the study. The flap was elevated with a cuff of gastrocnemius muscle under the skin paddle, and the distal pedicle was dissected until 5 cm over the lateral malleolus. The donor site is primarily closed or skin-grafted. From March 2004 to August 2006, this distally based superficial sural fasciomusculocutaneous flap was applied to nine patients. All the defects resulted from traumatic injuries of the distal third of the leg, ankle, or foot, combined with bone or tendon exposure. Two flaps developed minor distal skin necrosis that recovered uneventfully with conservative therapy. The other flaps had an adequate postoperative evolution with good blood supply, contour, and function. The superficial sural fasciomusculocutaneous flap is a simple and consistent alternative for distal lower limb reconstruction, particularly when microsurgery is not available.


The translaminar approach to canalicular and cranio-dorsolateral lumbar disc herniations.
The interlaminar approach is the standard procedure for most disc herniations in lumbar spine surgery. However, in cranially extruded disc herniations including canalicular herniations, partial or complete facetectomy is necessary with increased risk of postoperative spinal instability. We present the translaminar technique which allows a more direct and less destructive operative approach. 30 patients using the translaminar fenestration were analysed by a postoperative follow-up of 6 weeks and one year. The mean-age was 57.2 years. For resection of the disc herniation, a small round or oval fenestration (6-8 mm) in the hemilamina, craniomedially to the facet joint, was performed. No patient received a partial or total facetectomy. The majority of affected discs were at the L4-L5 level (53%). An extruded fragment was found in 28 patients (93%). In 5 patients bleeding from epidural veins complicated the intra-operative course. In 50% the nerve root was visually exposed. 15 patients (50%) had an intervertebral discectomy additional to the fragment excision. One patient was re-operated on after 10 days because of persisting radicular pain by using the same translaminar approach. 28 patients showed complete or nearly complete relief of radicular pain. Using this approach we have seen no major complication or clinical instability during a follow-up of at least one year. The translaminar approach is an effective and minimally invasive technique in both canalicular and cranio-dorsolateral disc herniations. It gives an additional possibility to avoid partial removal of the facet joints, can be performed in all lumbar segments and preserves structures important for segmental spinal stability. The approach allows access to the extruded disc fragment and intervertebral disc space comparable to classical approaches and is a frequently used operative technique in our department.


Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families.
The risk for autoimmunity and subsequently type 1 diabetes is 10-fold higher in children with a first-degree family history of type 1 diabetes (FDR children) than in children in the general population (GP children). We analyzed children with high-risk HLA genotypes (n = 4,573) in the longitudinal TEDDY birth cohort to determine how much of the divergent risk is attributable to genetic enrichment in affected families. Enrichment for susceptible genotypes of multiple type 1 diabetes-associated genes and a novel risk gene, BTNL2, was identified in FDR children compared with GP children. After correction for genetic enrichment, the risks in the FDR and GP children converged but were not identical for multiple islet autoantibodies (hazard ratio [HR] 2.26 [95% CI 1.6-3.02]) and for diabetes (HR 2.92 [95% CI 2.05-4.16]). Convergence varied depending upon the degree of genetic susceptibility. Risks were similar in the highest genetic susceptibility group for multiple islet autoantibodies (14.3% vs .12.7%) and diabetes (4.8% vs. 4.1%) and were up to 5.8-fold divergent for children in the lowest genetic susceptibility group, decreasing incrementally in GP children but not in FDR children. These findings suggest that additional factors enriched within affected families preferentially increase the risk of autoimmunity and type 1 diabetes in lower genetic susceptibility strata.


Transportability of Trial Results Using Inverse Odds of Sampling Weights.
Increasingly, the statistical and epidemiologic literature is focusing beyond issues of internal validity and turning its attention to questions of external validity. Here, we discuss some of the challenges of transporting a causal effect from a randomized trial to a specific target population. We present an inverse odds weighting approach that can easily operationalize transportability. We derive these weights in closed form and illustrate their use with a simple numerical example. We discuss how the conditions required for the identification of internally valid causal effects are translated to apply to the identification of externally valid causal effects. Estimating effects in target populations is an important goal, especially for policy or clinical decisions. Researchers and policy-makers should therefore consider use of statistical techniques such as inverse odds of sampling weights, which under careful assumptions can transport effect estimates from study samples to target populations.


Production of vascular endothelial growth factors from human lung macrophages induced by group IIA and group X secreted phospholipases A2.
Angiogenesis and lymphangiogenesis mediated by vascular endothelial growth factors (VEGFs) are main features of chronic inflammation and tumors. Secreted phospholipases A(2) (sPLA(2)s) are overexpressed in inflammatory lung diseases and cancer and they activate inflammatory cells by enzymatic and receptor-mediated mechanisms. We investigated the effect of sPLA(2)s on the production of VEGFs from human macrophages purified from the lung tissue of patients undergoing thoracic surgery. Primary macrophages express VEGF-A, VEGF-B, VEGF-C, and VEGF-D at both mRNA and protein level. Two human sPLA(2)s (group IIA and group X) induced the expression and release of VEGF-A and VEGF-C from macrophages. Enzymatically-inactive sPLA(2)s were as effective as the active enzymes in inducing VEGF production. Me-Indoxam and RO092906A, two compounds that block receptor-mediated effects of sPLA(2)s, inhibited group X-induced release of VEGF-A. Inhibition of the MAPK p38 by SB203580 also reduced sPLA(2)-induced release of VEGF-A. Supernatants of group X-activated macrophages induced an angiogenic response in chorioallantoic membranes that was inhibited by Me-Indoxam. Stimulation of macrophages with group X sPLA(2) in the presence of adenosine analogs induced a synergistic increase of VEGF-A release and inhibited TNF-alpha production through a cooperation between A(2A) and A(3) receptors. These results demonstrate that sPLA(2)s induce production of VEGF-A and VEGF-C in human macrophages by a receptor-mediated mechanism independent from sPLA(2) catalytic activity. Thus, sPLA(2)s may play an important role in inflammatory and/or neoplastic angiogenesis and lymphangiogenesis.


Atomistic to Mesoscopic Modelling of Thermophysical Properties of Graphene-Reinforced Epoxy Nanocomposites.
This research addresses the need for a multiscale model for the determination of the thermophysical properties of nanofiller-enhanced thermoset polymer composites. Specifically, we analyzed the thermophysical properties of an epoxy resin containing bisphenol-A diglyceryl ether (DGEBA) as an epoxy monomer and dicyandiamide (DICY) and diethylene triamine (DETA) as cross-linking agents. The cross-linking process occurs at the atomistic scale through the formation of bonds among the reactive particles within the epoxy and hardener molecules. To derive the interatomic coarse-grained potential for the mesoscopic model and match the density of the material studied through atomic simulations, we employed the iterative Boltzmann inversion method. The newly developed coarse-grained molecular dynamics model effectively reproduces various thermophysical properties of the DGEBA-DICY-DETA resin system. Furthermore, we simulated nanocomposites made of the considered epoxy additivated with graphene nanofillers at the mesoscopic level and verified them against continuum approaches. Our results demonstrate that a moderate amount of nanofillers (up to 2 wt.%) increases the elastic modulus and thermal conductivity of the epoxy resin while decreasing the Poisson's ratio. For the first time, we present a coarse-grained model of DGEBA-DICY-DETA/graphene materials, which can facilitate the design and development of composites with tunable thermophysical properties for a potentially wide range of applications, e.g., automotive, aerospace, biomedical, or energy ones.


Generation and characterization of monoclonal antibodies against Klebsiella pneumoniae.
The present work was undertaken with the aim to generate highly specific monoclonal antibodies (MAb) targeted against Klebsiella pneumoniae that could be incorporated into a highly sensitive and simple ELISA (plate and dot) based system for the rapid identification of K. pneumoniae strains. Four murine monoclonal antibodies (KP-1, KP-2, KP-3, and KP-4) reactive to K. pneumoniae were generated and stabilized. Monoclonal antibodies KP-1 and KP-2 were of IgM type and KP-3 and KP-4 were of IgG type. All of the MAbs were found to be specific to K. pneumoniae strain, as they did not show any cross reactivity when tested with 22 different species and stains of members of the Enterobacteriaceae group. In Western blotting with whole cell lysate antigens of K. pneumoniae, KP-3 and KP-4 were found to react with 70 to 110 kDa regions. The nature of the epitope recognized by all four monoclonal antibodies was carbohydrate as determined by periodate and trypsin treatment of antigens. The monoclonal antibodies were further evaluated on 20 biochemical identified K. pneumoniae strains. The KP-3 and KP-4 monoclonal antibodies produced strong reactions with 19 and 18 strains, respectively, by dot-ELISA. KP-1 and KP-2 (IgM) did not show reaction in dot-ELISA but by agglutination test these could detect 11 and 13 strains, respectively.


Sickle cell trait in French West Indian elite sprint athletes.
The aim of this study was to establish the percentage of sickle cell trait (SCT) carriers among French West Indian sprinters selected for the French National Team in 2000. The investigation determined the number of SCT carriers and the number of national records they had established. Sixteen athletes were indexed (6 males and 10 females). The athletes were within the ranges of 20-33 years, 161-186 cm and 60-80 kg. The results showed the presence of SCT carriers in this population among whom three were SCT carriers (2 males and 1 female) (18.75%). Moreover, there is a significantly higher percentage of titles and records held by the SCT carriers (38.6% and 50%, respectively). In conclusion, this study shows that sickle cell trait carriers are able to perform sprint exercises at the highest levels, and it further indicates that brief and explosive exercise involving mainly the alactic anaerobic metabolism may be enhanced by HbS.


Cobalt(II)-Catalyzed Intermolecular Aminocarbonylation of Indoles with Amines.
A cobalt(II)-catalyzed C2-H carbonylation of indoles with amines toward indole-2-carboxamides has been developed. By employing Co(OAc)2·4H2O as an inexpensive catalyst and using benzene-1,3,5-triyl triformate (TFBen) as the CO surrogate, a variety of indole-2-carboxamide derivatives were produced in moderate to high yields. Additionally, several bioactive-molecule-related compounds can be applied as substrates, as well.


Calcifediol in chronic renal insufficiency. Skeletal response.
Quantitative histology of thin, nondecalcified sections was performed on sequential bone biopsy specimens from five patients undergoing long-term hemodialysis and treated with calcifediol (25-hydroxycholecalciferol) for periods of three to nine months. With increase of intestinal absorption of calcium and decline of circulating immunoreactive parathyroid hormone and alkaline phosphatase, the bones of each patient exhibited striking histological improvement. The group as a whole showed statistically significant decreases in osteoclast number and in the percentages of osteoid surface covered by active osteoblasts. Marrow fibrosis was either eliminated or strikingly decreased in each patient. Osteoid volume significantly declined in four of five patients. In patients with osteitis fibrosa as the predominant histological lesion, calcifediol therapy resulted in decreased calcification front activity. Increased activity was the result when osteomalacia predominated.


[Celiac disease].
Celiac disease is an enteropathy due to gluten intake in genetically predisposed individuals (HLA DQ2/DQ8). Celiac disease occurs in adults and children at rates approaching 1% of population in Europe and USA. Clinical features observed in celiac disease are extremely various and anaemia, oral aphthous stomatis, amenorrhea or articular symptoms may be the only presenting manifestations. Diagnosis relies on the evidence of histological villous atrophy in proximal small bowel and the presence of specific serum antibodies. Treatment relies on eviction of gluten (wheat, barley, rye) from diet. Gluten free diet allows prevention of malignant complications such as small bowel adenocarcinoma and lymphoma, and osteopenia. The main cause of resistance to gluten free diet is its poor observance. If not the case, serious complications of celiac disease, such as clonal refractory celiac sprue and intestinal T-cell lymphoma should be suspected. Current therapeutic challenges concern alternative to gluten free diet and new efficient treatments of lymphomatous complications.


Mutations of p53 associated with pancreatic cancer and therapeutic implications.
Pancreatic adenocarcinoma is a malignancy with rising incidence and grim prognosis. Despite improvements in therapeutics for treating metastatic pancreatic cancer, this disease is invariably fatal with survival time less than a few years. New molecular understanding of the pathogenesis of pancreatic adenocarcinoma based on efforts led by The Cancer Genome Atlas and other groups has elucidated the landscape of this disease and started to produce therapeutic results, leading to the first introduction of targeted therapies for subsets of pancreatic cancers bearing specific molecular lesions such as BRCA mutations. These efforts have highlighted that subsets of pancreatic cancers are particularly sensitive to chemotherapy. The most common molecular lesions in pancreatic adenocarcinomas are mutations in an oncogene KRAS and the TP53 gene that encodes for tumor suppressor protein p53. This paper will review the landscape of pancreatic cancers, focusing on mutations of p53, a major tumor suppressor protein, in pancreatic cancers and possible therapeutic repercussions.


Elevated exhalation of hydrogen peroxide and thiobarbituric acid reactive substances in patients with community acquired pneumonia.
Bacterial pneumonia involves influx of activated phagocytes into distal airways. These cells release oxidants including H2O2, that may be exhaled or induce peroxidative damage to lung tissues with formation of thiobarbituric reactive substances (TBARs). To determine whether concentrations of H2O2 and TBARs in exhaled breath condensate (EBC) is elevated and correlate with systemic response to pneumonia during 10 days of hospital treatment. The concentration of H2O2 and TBARs was measured in EBC of 43 inpatients with community acquired pneumonia (CAP) and 20 healthy never smoked subjects over 10 days and were accompanied by monitoring of WBC count, serum concentration of C-reactive protein (CRP) and peroxyl radical-trapping capacity. Patients with CAP exhaled 4.6-, 3.7-, 3.9-, 3.3-times more H2O2 than healthy controls at 1st, 3rd, 5th and 10th day of treatment (P<0.05), respectively. EBC concentrations of TBARs were elevated at 1st and 3rd day. H2O2 and TBARs levels decreased along with treatment course. Correlation (P<0.05) was found between H2O2 levels and CRP and WBC count (r = 0.31) at 1st day and between TBARs and CRP at 5th (r = 0.34) and 10th day (r = 0.46). The mean H2O2 exhalation estimated over ten days of treatment correlated with pneumonic chest X-ray score (r = 0.42), CRP levels (r = 0.46) and WBC count (r = 0.33) at admission (P<0.05). Pneumonia is accompanied by oxidative stress in airways that moderately correlates with intensity of systemic inflammatory response. Determination of H2O2 in EBC may be helpful for non-invasive monitoring of oxidants production during lower respiratory tract infection.


Increased expression of galectin-1 during the progression of cervical neoplasia.
Galectin-1, a member of the beta-galactoside-binding family, is widely expressed in epithelial and immune cells. It is involved in several normal and pathologic processes, such as cancer progression, metastasis, and immunobiology. Galectin-1 was found to be overexpressed in various cancer cells and the corresponding benign tissue. Therefore, it has been described as a marker for tumor progression in some malignancies. In the current study, the expression of galectin-1 was examined in 80 formalin-fixed, paraffin-embedded cervical tissues: 20 benign cervical specimen, 20 low-grade squamous intraepithelial lesions (LGSIL), 20 high-grade squamous intraepithelial lesions (HGSIL), and 20 invasive squamous cell carcinomas (ISCC). Immunohistochemical analyses showed that the intensity of the galectin-1 expression on stromal cells next to the transformed cells increased according to the pathologic grade: benign cervical tissue < LGSIL < HGSIL < ISCC (P < 0.001). The epithelial cells were always negative for galectin-1. These results suggest that galectin-1 expression on stromal cells increases with the histopathologic grade of cervical tissues, and it can be concluded that this increase is associated with the progression of cervical neoplasia.


Characteristics of bleeding complications in patients with anticoagulant treatment.
Anticoagulation treatment is effective in the prevention of stroke as well as deep venous thrombosis (DVT) and pulmonary embolism (PE). Its preventive benefit has to be balanced against possible bleeding complications. We sought to assess risk factors for the severity of bleeding events in patients under anticoagulant treatment. Clinical characteristics, type of anticoagulant treatment, bleeding site, risk factors and additional medication taken were analysed in patients with bleeding complications during an observation period of 12 months. Eighty-seven bleeding complications in 84 patients (mean age, 79 years; 51% female) were observed from January to December 2005 at the Department of Internal Medicine of the Cantonal Hospital of Aargau. Most bleeding complications occurred in the gastrointestinal tract (54%). The median time interval from the beginning of the anticoagulant treatment to the bleeding event was 34 months. Forty-nine percent of events occurred after a treatment time above 36 months. Age was not found to influence the severity of bleeding but the duration of anticoagulant treatment before the occurrence of a complication was significantly longer for older patients (p = 0.001). Our study shows no influence of age on severity of bleeding complications. Furthermore, in patients with advanced age complications occurred later in the treatment course than in younger patients. Overall we assessed various bleeding events in patients treated for over three years. Therefore we emphasize the importance of closely controlling patients on anticoagulant treatment in the later course of treatment and to take account of the anticoagulation when ordering new medication.


Pediatric Stevens-Johnson syndrome and toxic epidermal necrolysis in the United States.
Little is known about the epidemiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in children. We sought to determine the morbidity, mortality, and comorbid health conditions of SJS and TEN in US children. This was a cross-sectional study of the 2009 to 2012 Nationwide Inpatient Sample, which contains a representative 20% sample of all US hospitalizations. Sociodemographics, inflation-adjusted cost, length of stay, comorbidities, and mortality were analyzed using descriptive statistics and multivariate regression analyses. The incidences of SJS, SJS-TEN, and TEN were a mean 5.3, 0.8, and 0.4 cases per million children per year in the US, respectively. Prolonged length of stay and higher costs of care (SJS: 9.4 ± 0.6 days, $24,947 ± $3171; SJS-TEN: 15.7 ± 1.5 days, $63,787 ± $8014; TEN: 20.4 ± 6.3 days, $102,243 ± $37,588) were observed compared with all other admissions (4.6 ± 0.1 days, $10,496 ± $424). Mortality was 0% for SJS, 4% for SJS-TEN, and 16% for TEN. In regression models, predictors of mortality included renal failure (adjusted OR [aOR] 300.28, 95% confidence interval [CI] 48.59->999.99), malignancy (aOR 54.33, 95% CI 9.40-314.22), septicemia (aOR 30.45, 95% CI 7.91-117.19), bacterial infection (aOR 20.38, 95% CI 5.44-76.36), and epilepsy (aOR 5.56, 95% CI 1.37-26.2). Data regarding treatment were not available. Date of diagnosis of comorbidities was not present, precluding temporal analysis. Pediatric SJS/TEN poses a substantial health burden in the United States.


Assessing levels of POPs in air over the South Atlantic Ocean off the coast of South America.
The occurrence of persistent organic pollutants (POPs) in the atmosphere of the near-coast South Atlantic Ocean was studied. Air samples were collected using a high-volume air sampler (filter and polyurethane foam) on board the Argentinean research cruise R/V Puerto Deseado (CONICET). Samples were analyzed for 50 polychlorinated biphenyl (PCBs), 22 organochlorine pesticides (OCPs) and 14 polybrominated diphenyl ethers (PBDEs). These POPs classes showed a trend of decreasing levels from near-shore to open ocean sites. OCPs and PCBs were in the same order of magnitude (2.71-87.1pg/m(3) and 9.56-130pg/m(3), respectively) while PBDEs levels were significantly lower (0.69-2.58pg/m(3)). Dichlorodiphenyltrichloroethanes (DDTs), endosulfans, chlordanes, hexachlorocyclohexanes (HCHs) and heptachlors were between 0.20 and 17.8pg/m(3), while drines and hexachlorobenzene (HCB) were at lower levels (0.28-3.71pg/m(3)). The most frequently detected PCBs were congeners 32, 28, 44, 52, 95, representing >50% of the total. The PBDEs congener pattern was dominated by congener 209 (70%), followed by 47 and 99 (16% and 7%, respectively). Air parcel back trajectories for the study period provided few insights as trajectories mainly stemmed from the open ocean with limited inputs from continental sources. These results indicate that the concentration of POPs (namely PCBs, OCPs, and PBDEs) in air remain elevated in the near-shore environment and then drop-off substantially beyond a distance of about 400km. This has implications for the loading of POPs and delivery to the marine environment in the near coastal zone.


Hearing loss and speech perception in noise difficulties in Fanconi anemia.
Fanconi anemia is a hereditary chromosomal instability disorder. Hearing loss and ear abnormalities are among the many manifestations reported in this disorder. In addition, Fanconi anemia patients often complain about hearing difficulties in situations with background noise (speech perception in noise difficulties). Our study aimed to describe the prevalence of hearing loss and speech perception in noise difficulties in Dutch Fanconi anemia patients. Retrospective chart review. A retrospective chart review was conducted at a Dutch tertiary care center. All patients with Fanconi anemia at clinical follow-up in our hospital were included. Medical files were reviewed to collect data on hearing loss and speech perception in noise difficulties. In total, 49 Fanconi anemia patients were included. Audiograms were available in 29 patients and showed hearing loss in 16 patients (55%). Conductive hearing loss was present in 24.1%, sensorineural in 20.7%, and mixed in 10.3%. A speech in noise test was performed in 17 patients; speech perception in noise was subnormal in nine patients (52.9%) and abnormal in two patients (11.7%). Hearing loss and speech perception in noise abnormalities are common in Fanconi anemia. Therefore, pure tone audiograms and speech in noise tests should be performed, preferably already at a young age, because hearing aids or assistive listening devices could be very valuable in developing language and communication skills. 4. Laryngoscope, 127:2358-2361, 2017.


Clinical experience with radiotracer-guided thoracoscopic biopsy of small, indeterminate lung nodules.
Although computed tomography lung-screening programs report a 31% to 51% incidence of subcentimeter pulmonary nodules, 85% are too small to biopsy or interrogate with positron emission spectroscopy scans. We developed a technique using transthoracic percutaneous radiotracer injection with thoracoscopic radioprobe localization and excision for small pulmonary nodules. This report describes our series of the first 46 patients evaluated with this technique. Forty-six patients (79% smokers; 52% males; median age, 64 years) were evaluated. Patient selection was based on the surgeon's anticipated difficulty in thoracoscopically locating small nodules because of lesion size or location. Computed tomographic-guided injection of radiotracer solution was made into or adjacent to the nodule the day of surgery. Intraoperative gamma probe localization, followed by thoracoscopic excision of the lesion, was subsequently performed. Median nodule size was 9 mm (range, 3 to 22 mm), and median depth was 5 mm (range, 0 to 50 mm). Forty-four (96%) of the lesions were successfully localized and excised. Median time from injection to surgery was 270 minutes. Failures were the result of inadvertent pleural or chest wall radiotracer placement. Forty-six percent (21 of 46) of the lesions were malignant, of which 71% (15 of 21) were primary lung cancers. Patients with lung cancer underwent lobectomy or segmentectomy. Fourteen of 15 were stage IA, whereas 1 was stage IIIB (6 mm primary with 4 mm intralobar metastasis). Complications were three pneumothoraces at the time of radiotracer injection. Computed tomography-guided radiotracer localization of small pulmonary nodules combined with thoracoscopic excisional biopsy is feasible and safe. This technique successfully localized and excised the nodule in 96% of cases.


PHASE THREE OF WRIGHT'S SHIFTING-BALANCE THEORY.
We examine the third phase of Wright's shifting-balance theory of evolution, the exportation by migration of favorable gene combinations from a fitter subgroup to the rest of the population. The equations are deterministic and are studied numerically. Most of the models studied involve 2-9 loci in which all intermediates between two extreme genotypes are equally unfit. If the favored combination consists of dominant alleles, it is usually fixed even if the migration rate is two orders of magnitude less than the selection coefficient, and if the combination is recessive, one order. Although Wright thought of migration as being essentially one-way, two-way migration does not significantly alter the results. We conclude that, whatever weaknesses the Wright theory may have, they are not in phase III.


Accuracy of ultrasound biometry in the prediction of macrosomia: a systematic quantitative review.
To determine the accuracy of ultrasonographically estimated fetal weight (EFW) and abdominal circumference (AC) in the prediction of macrosomia. Systematic quantitative review. Studies were identified without language restrictions from MEDLINE (1966-2003), EMBASE (1980-2003), Cochrane Library (2003:4), SCISEARCH (1974-2003) and manual searching of bibliographies of known primary and review articles. Studies were selected if accuracy of ultrasonographically EFW or AC was evaluated for predicting macrosomia using birthweight as the reference standard. Data were extracted on study characteristics, quality and accuracy. Data were pooled to produce summary receiver operating characteristic curves (sROC) for studies with various test thresholds. Summary likelihood ratios for positive (LR+) and negative (LR-) test results were generated for an EFW of 4000 g and an AC of 36 cm for predicting birthweight of over 4000 g. Birthweight over various thresholds. There were 36 primary articles consisting of 63 accuracy studies (51 evaluating the accuracy of EFW, and 12 accuracy of fetal AC), including a total of 19,117 women. The sROC area for EFW was not different from the area for fetal AC (0.87 vs 0.85, P= 0.91). For predicting a birthweight of over 4000 g, the summary LRs were 5.7 (95% CI: 4.3 to 7.6) for a positive test and 0.48 (95% CI: 0.38 to 0.60) for a negative test, using Hadlock's method of ultrasonographically estimating fetal weight. For ultrasound fetal AC of 36 cm, the respective LRs for predicting a birthweight over 4000 g were 6.9 (95% CI: 5.2 to 9.0) and 0.37 (0.30-0.45). There is no difference in accuracy between ultrasonographically EFW and AC in the prediction of a macrosomic baby at birth. A positive test result is more accurate for ruling in macrosomia than a negative test result for ruling it out.


Modern Innovative Solutions to Improve Outcomes in Severe Asthma: Protocol for a Mixed Methods Observational Comparison of Clinical Outcomes in MISSION Versus Current Care Delivery.
Asthma that is poorly controlled and undertreated can progress to more severe disease that is associated with high levels of unscheduled care that requires high-cost therapy, leading to a significant health economic burden. The identification and appropriate referral to a specialist asthma service is also often delayed by several months or years because of poor recognition and understanding of symptom severity. Current severe asthma services may take several months to provide a comprehensive multidisciplinary assessment, often necessitating multiple hospital visits and costing up to £5000 per patient. This study aims to evaluate whether a new service model could identify poorly controlled and potentially severe asthma much earlier in the patient pathway, and then compare clinical outcomes between this new care model with standard care. Modern Innovative Solutions to Improve Outcomes in (MISSION) Severe Asthma is a novel service model developed by asthma specialists from Portsmouth and Southampton severe asthma services. MISSION Severe Asthma identified patients with poorly controlled disease from general practice databases who had not been under secondary outpatient care in the last 12 months or who were not known to secondary care. In 1- or 2-stop assessments, a thorough review of diagnosis, disease phenotype, and control is undertaken, and clinical outcomes collected at baseline. A variety of clinical outcomes will be collected to assess the service model. The results will be reported in February 2020. This protocol outlines a mixed methods study to assess the impact on disease control, unscheduled health care usage, and quality of life in patients seen in the MISSION clinic compared with a closely matched cohort who declined to attend. DERR1-10.2196/9585.


WO3 nanoparticles on MCM-48 as a highly selective and versatile heterogeneous catalyst for the oxidation of olefins, sulfides, and cyclic ketones.
[reaction: see text] It is shown that nanosized WO(3) particles supported on MCM-48 work as a highly efficient and selective heterogeneous catalyst for the oxidation of olefins, sulfides, and cyclic ketones using hydrogen peroxide or peracetic acid. The catalytic activity of the supported tungstate was dependent on the nature of the supporting materials and particle size. The catalyst system employs environmentally benign oxidants in halide-free solvents, and it does not require phase-transfer agents and pH control.


Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology.
In malignant pleural mesothelioma (MPM), most patients first present with pleural effusion; thus, cytologic analysis is the primary diagnostic approach. However, the cytologic distinction between MPM and reactive mesothelial cells (RMCs) in effusions can be extremely difficult due to the lack of both well-established immunocytochemical markers and definite cytological criteria for MPM. Moreover, the existence of both MPM cells and RMCs in effusions from the same patient makes the differentiation even more challenging. Homozygous deletion of the 9p21 locus, the site of the cyclin-dependent kinase inhibitor 2A/p16 (CDKN2A/p16) gene, frequently occurs in MPM but has never been reported in RMCs. The aim of this study was to define the cytomorphological characteristics of MPM cells, identified by the presence of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH). For this purpose, cells on smear preparations were recorded using a virtual microscope system and were subjected to FISH analysis. Thereafter, 9p21 homozygous deletion-positive cells were identified in the recorded virtual slides, followed by analysis of their morphological characteristics. Mesothelioma cells positive for the 9p21 homozygous deletion exhibited significantly more frequent cell-in-cell engulfment, multinucleation (more than 2 nuclei), and larger multicellular clusters composed of more than 10 cells than did 9p21 deletion-negative RMCs. Possible cutoff values are also proposed for these morphological markers to differentiate MPM cells from RMCs. These morphological differences and cutoff values are useful for cytological differentiation of mesothelioma cells from RMCs. In addition, the novel technique of a combination of virtual microscopy and FISH is introduced for tumor morphological analysis.


A combined approach for individualized lymphadenectomy in gastric cancer patients.
Introduction: Gastric cancer ranks as the fifth most common cancer globally. The presence of lymph node metastasis is a significant prognostic factor influencing survival. Postoperative morbidity and nodal staging accuracy are heavily affected by the extent of lymph node dissection. Our study aimed to explore the potential integration of two contemporary methods, sentinel node navigation surgery (SNNS) and the Maruyama Computer Program (MCP), to improve the accuracy of nodal staging. Materials and methods: We conducted a prospective data collection involving patients with gastric adenocarcinoma from 2008 to 2018 at the Department of Surgery, University of Debrecen, Hungary. Data from 100 consecutive patients were collected. The primary and secondary endpoints included evaluating the rate of node-negative patients and the diagnostic accuracy of our combined approach. Results: Sentinel node mapping was successful in 97 out of 100 patients. We found that using the threshold value of the Maruyama Index (MI) ≥ 28, all metastatic stations of sentinel-node-negative patients could be identified. Our method achieved 100% sensitivity and negative predictive value, with a specificity of 60.42% (95% CI = 46.31%-72.98%). Discussion: The combined application of SNNS and MCP has proven to be an effective diagnostic technique in the synergistic approach for identifying metastasis-positive lymph node stations. Despite its limitations, this combination may assist clinicians in customizing lymphadenectomy for gastric cancer patients.


Cytological, immunocytochemical and biochemical cerebrospinal fluid investigations in selected central nervous system disorders of dogs.
Cerebrospinal fluid (CSF) obtained from 20 clinically healthy dogs and from 15 dogs affected by neurological disorders were examined for total and differential cell counts, immunocytochemistry for canine distemper virus antigen, total protein concentration and electrophoretic separation, and glucose and enzyme determination. Dogs affected by canine distemper showed an increase in macrophages, presence of specific inclusion bodies, and an increase in total protein concentration and gamma-globulin fraction. In bacterial meningoencephalomyelitis pleocytosis, increase of total proteins with special regard to high molecular weight proteins, elevated levels of lactate dehydrogenase (LDH), alterations of LDH isoenzyme profile, and decrease in glucose levels were detected; inflammatory disorders were more often characterized by an increase in LDH level, while in non-inflammatory disorders (hydrocephalus and spinal cord neoplasia) no variation in LDH levels was detected. Analysis of CSF in dogs appears relatively easy to perform and may help in establishing the condition of the blood-brain barrier as well as in the diagnosis of neurological disorders.


Social inequality and general practitioner utilisation: assessing the effects of financial barriers on the use of care by low income groups.
To evaluate the extent to which financial barriers are still important deterrents to the utilisation of primary care by low income groups and to examine whether the willingness of patients to switch doctors is associated with ability to pay. A practice and a population survey was used to compare the importance of price barriers, patient satisfaction and utilisation rates in two low income areas of Christchurch. Comparisons are made on the basis of gender, age, perceived health status, housing tenure, benefit status, income and ethnicity. Despite the introduction of the Community Services Card, delays in using services because of the cost of care remain significant for many groups of patients, including cardholders themselves. The removal of price barriers at the free clinic raised utilisation rates for all groups. Patterns of use at the free clinic show a consistent inverse relationship between income and consultation rates. However, this was not evident among patients in the population sample who continued to use fee-for-service providers. Further, the results do not support arguments that patients are insensitive to price when changing their doctors. Despite the removal of part-charges for children, financial barriers remain significant for many low income adults. To a large extent these barriers reflect the nature of welfare reform, particularly the detrimental effects of pro-market housing policies in limiting the disposable incomes of poorer New Zealanders.


Workplace violence at government sites.
A government agency and its contractors employing nearly 96,000 workers throughout the country was surveyed for documented incidents of violence in the workplace. Thirty-five occupational medicine and related professionals (36% of those surveyed) from 27 locations returned the questionnaire. Of the responders, 20 individuals reported 74 incidents of workplace violence, with nearly 30% of these occurrences involving weapons, including 11 with guns. In a companion survey of human resource departments from 28 locations, there were 16 responders (57% of those surveyed) with 13 of them documenting 96 additional incidents. No duplicate reporting of the same event occurred between the two surveys. Approximately 70% of the agency workers were employed in locations covered by the 51 responders. Although the data are limited, the number of incidents and level of violence appear to be increasing over time. Of the 108 incidents for which time of occurrence was known, 32 were defined as "very serious," which included physical assault, threat or assault with a weapon, murder, suicide, or stalking. Verbal threats, verbal assaults, and vandalism were defined as "serious" incidents. A Cochran-Armitage trend test for an increasing proportion over time of "very serious" vs. "serious" events was statistically significant, with a P-value of 0.026.


Role of Chlamydia trachomatis and mycoplasmas in chronic prostatitis. A review.
Acute bacterial prostatitis caused by common urinary tract pathogens is an infrequent disease, and diagnostic difficulties are rarely encountered. On the other hand, chronic prostatitis is a common disease requiring rather elaborate diagnostic procedures. We applied the localization protocol of the four-specimen technique and combined quantitative determinations of microorganisms and quantitative cytologic analysis plus, in chlamydial infections, serologic investigations. Our studies provide good evidence that Ureaplasma urealyticum and Chlamydia trachomatis must be considered etiologic agents in many cases of chronic bacterial prostatitis. These unconventional microorganisms are assumed to infect the prostate by way of intracanalicular ascension from the urethra.


[Applied methods instead of autologous nerve transplantation in the reconstruction of nerve injuries on the hand].
For a long time in the clinical practice the autologous nerve transplants are used in reconstruction of the segmental defects of injured hand nerves. The published outcomes, especially in case of the motor and mixed (sensory and motor) nerves, however, were not satisfactory. Hence, it remained a problem and in the focus of research. The author aimed to study this topic and drawing conclusions in his literary review publication. According to the recent results, the replacement of the autologous nerve transplants with other materials (e.g. nerve conduits, various allografts, etc.) has shown good outcomes in mixed nerves too, if the distance of the resected nerve ends do not exceed 6 mm and the diameter of the nerves were not more than 3-7 mm. The applications of these methods have shown poor results, if the defect and/or the nerve diameter were larger. So, in these cases the autologous nerve transplantation remains the optimal management in the future. Orv Hetil. 2017; 158(30): 1163-1167.


Growth-suppressive function of phosphatidylethanolamine-binding protein in anaplastic thyroid cancer.
A cDNA microarray analysis of anaplastic thyroid cancer cell lines (ACL) was recently performed and the down-regulation of phosphatidylethanolamine-binding protein (PBP) [RAF kinase inhibitor protein (RKIP)] in ACL compared to normal thyroid tissues was identified. The expression levels of PBP in primary anaplastic and papillary thyroid cancer, thyroid cancer cell lines (anaplastic, papillary and follicular) and several normal human organs were examined. To examine the function of PBP, cell-growth assays were performed. PBP expression was reduced in anaplastic thyroid cancers, compared to either normal thyroid tissues or differentiated thyroid cancers. PBP was expressed ubiquitously in normal human tissues. Exogenous PBP expression suppressed ACL growth, and suggested a tumor suppressive function of PBP in ACL. This is the first report demonstrating that PBP may be a tumor suppressor whose loss is associated with development of anaplastic thyroid cancer from differentiated thyroid cancer.


Photo-induced spatial gradient network for shape memory polymer with pattern-memorizing surface.
Incorporating a pattern-memorizing surface into a multi-functional shape memory polymer (SMP) offers various extraordinary opportunities for their engineering applications. However, current memory-patterned approaches prepared by artificial loading are at the cost of initial balance, whose potential is greatly limited by the internal relationship between thermodynamic equilibrium and the entropy-driven pattern-memorizing cycle. Here, a robust yet effective strategy is presented for fabricating a spontaneous pattern on a poly(styrene-block-butadiene-block-styrene) (SBS)-based SMP with a gradient crosslinking network via molecular diffusion for equilibrium. Benefiting from the photo-induced diffusion of maleimide, the resulting steady-state pattern as a permanent shape ensures the recovery of morphology, and the gradient network formed by the diffusion-regulated spatial Diels-Alder (D-A) crosslinking reaction makes the pattern memory cycle from existence to elimination possible. Furthermore, taking advantage of an uneven structural network, the shape reconfigurations from 2D patterned sheets to 3D configurations with a patterned surface can be achieved conveniently through a shape memory effect, simplifying programming setups. In addition, this type of 3D shape also can shift back to a 2D patterned film via an inverse D-A decrosslinking reaction upon thermal treatment. This straightforward approach for fabricating a pattern of a single layer on an SMP surface with a spatial gradient network opens a new avenue for functional smart materials, which expands the technological perspectives in many fields of flexible electronics, smart actuators, switching sensors and soft robotics.


In vitro effects of the co-release of icariin and strontium from bioactive glass submicron spheres on the reduced osteogenic potential of rat osteoporotic bone marrow mesenchymal stem cells.
Osteoporosis is a metabolic disease that affects bone tissue and is highly associated with bone fractures. Typical osteoporosis fracture treatments, such as bisphosphonates and hormone replacement, present important challenges because of their low bioavailability on the site of action. Options to overcome this issue are systems for the local release of therapeutic agents such as bioactive glasses containing therapeutic molecules and ions. These agents are released during the dissolution process, combining the drugs and ion therapeutic effects for osteoporosis treatment. Among the therapeutic agents that can be applied for bone repair are strontium (Sr) ion and phytopharmaceutical icariin, which have shown potential to promote healthy bone marrow stem cells osteogenic differentiation, increase bone formation and prevent bone loss. Submicron Sr-containing bioactive glass mesoporous spheres with sustained ion release capacity were obtained. Icariin was successfully incorporated into the particles, and the glass composition influenced the icariin incorporation efficiency and release rates. In this work, for the first time, Sr and icariin were incorporated into bioactive glass submicron mesoporous spheres and the in vitro effects of the therapeutic agents release were evaluated on the reduced osteogenic potential of rat osteoporotic bone marrow mesenchymal stem cells, and results showed an improvement on the reduced differentiation potential.


Vector autoregressive modeling analysis of frequently sampled oral glucose tolerance test results. 1. A new method for quantifying insulin resistance and secretion.
To elucidate abnormalities in the feedback relationships between plasma glucose and plasma insulin levels in diabetic patients, we have introduced the vector autoregressive modeling method as a new for tool feedback analysis. This technique was applied to plasma glucose and insulin level data from a series of 977 frequently-sampled oral glucose tolerance tests (FS-OGTT). Neither special instruments nor medications were used in FS-OGTT. We were able to predict the degree of the plasma glucose response occurring after an impulse-like increase in plasma insulin at 1 mU/mL, as well as the plasma insulin response triggered by an impulse-like increase in plasma glucose at 1 mg/dL, in the form of "impulse response curves". The predicted impulse response curve of glucose to insulin gradually changed from negative to positive with incremental changes in the fasting plasma glucose level, reflecting increased insulin resistance. Furthermore, the response of insulin to glucose decreased in a stepwise fashion with the incremental changes in the fasting plasma glucose level. Our findings confirm the usefulness of impulse response curves as clinical indicators. In addition, analytical data point to a possible contribution of excessive hepatic glucose production to the pathogenesis of the insulin resistance in non-insulin-dependent diabetes mellitus.


An integrative re-evaluation of Typhlatya shrimp within the karst aquifer of the Yucatán Peninsula, Mexico.
The Yucatán Peninsula, Mexico is a carbonate platform well-known for extensive karst networks of densely stratified aquifer ecosystems. This aquifer supports diverse anchialine fauna, including species of the globally distributed anchialine shrimp genus Typhlatya (Atyidae). Four species (T. campecheae, T. pearsei, T. dzilamensis and T. mitchelli) are endemic to the Peninsula, of which three are federally listed in Mexico. This first integrative evaluation (i.e., molecular, morphological, broad geographic and type locality sampling, and environmental data) of Yucatán Typhlatya reveals considerable species identity conflict in prior phylogenetic assessments, broad species ranges, syntopy within cave systems and five genetic lineages (of which two are new to science). Despite sampling from the type locality of endangered T. campecheae, specimens (and molecular data) were indistinguishable from vulnerable T. pearsei. Ancestral/divergence reconstructions support convergent evolution of a low-salinity ancestor for a post-Paleogene arc Yucatán + Cuba Typhlatya clade within the anchialine Atyidae clade. A secondary adaptation for the coastal-restricted euryhaline (2-37 psu), Typhlatya dzilamensis (unknown conservation status) was identified, while remaining species lineages were low-salinity (< 5 psu) adapted and found within the meteoric lens of inland and coastal caves. This study demonstrates the need for integrative/interdisciplinary approaches when conducting biodiversity assessments in complex and poorly studied aquifers.


Saliva and dental implants.
This is a review and update of the: (1) interaction of dental implants with the environment, and (2) effects of salivary contamination on the load of implant prostheses.


Analysis of density changes and chemotactic receptors of leukocytes from chronic hemodialysis and peritoneal dialysis patients.
Analysis of standard Ficoll-Hypaque (density = 1.077 g/ml) separation profiles of peripheral white blood cells (WBC) from patients undergoing hemodialysis (HD) demonstrated that dialysis caused a marked decrease in the density of polymorphonuclear leukocytes (PMN) resulting in about 50% of these cells separating with the mononuclear cells. In vitro exposure of normal control peripheral blood to HD membranes as well as to the purified chemotactic factors C5a, C5ades-Arg, and formyl-Met-Leu-Phe (fMLP) also resulted in PMN density changes which altered the Ficoll-Hypaque separation profiles of WBC. Therefore, these results imply that C5a generation, resulting from complement activation by the HD membrane, induced the density changes in the PMN from HD patients. Further studies using flow cytometry and fluorescein-labeled chemotactic factors (C5a, formyl-Met-Leu-Phe-Lys [fMLPL] and casein) indicated that HD patients had a significant reduction in the ability of their PMN and monocytes to bind C5a. This contrasted with the findings of no significant difference in the percentage or fluorescence intensity of HD patients' PMN or monocytes binding casein or fMLPL. Functional studies to analyze chemotactic-factor-mediated responses indicated that there was a decreased ability of HD patients' PMN and monocytes to generate superoxide anion, produce H2O2 and release myeloperoxidase in response to both C5a and fMLP. Additional studies evaluated the binding of chemotactic factors to PMN and monocytes from normal blood following passage through a hemodialyzer and from patients undergoing HD. Analysis of receptor binding by control cells passed through the dialyzer showed that there was a progressive decrease in the percentage of C5a-receptor-positive PMN and monocytes but no change with casein or fMLPL. In contrast, peripheral PMN and monocytes from chronic renal failure patients on HD showed no difference in C5a, casein or fMLPL receptors during the course of HD as compared to the predialysis period. This appears to be attributable to a difference in the regulation of the C5a that is generated as a result of the dialysis-membrane-induced activation of the complement system. Although C5a has been shown to be continuously generated during the course of HD, these patients show no modulation of their C5a receptors during the course of HD or when their whole blood is exposed to dialysis membrane fibers. These findings suggest that there are mechanisms functioning in chronically dialyzed patients to protect them from the effects of excessive C5a generation during HD.(ABSTRACT TRUNCATED AT 400 WORDS)


M2 Macrophages Play Critical Roles in Progression of Inflammatory Liver Disease in Hepatitis C Virus Transgenic Mice.
Macrophages in liver tissue are widely defined as important inflammatory cells in chronic viral hepatitis due to their proinflammatory activity. We reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) play significant roles in causing chronic hepatitis in hepatitis C virus (HCV) transgenic mice (S. Sekiguchi et al., PLoS One 7:e51656, 2012, http://dx.doi.org/10.1371/journal.pone.0051656). In addition, we showed that recombinant vaccinia viruses expressing an HCV nonstructural protein (rVV-N25) could protect against the progression of chronic hepatitis by suppression of macrophage activation. Here, we focus on the role of macrophages in liver disease progression in HCV transgenic mice and examine characteristic features of macrophages following rVV-N25 treatment. The number of CD11b(+) F4/80(+) CD11c(-) CD206(+) (M2) macrophages in the liver of HCV transgenic mice was notably increased compared to that of age-matched control mice. These M2 macrophages in the liver produced elevated levels of IL-6 and TNF-α. rVV-N25 infection suppressed the number and activation of M2 macrophages in liver tissue. These results suggested that inflammatory cytokines produced by M2-like macrophages contribute to the induction of chronic liver inflammation in HCV transgenic mice. Moreover, the therapeutic effect of rVV-N25 might be induced by the suppression of the number and activation of hepatic macrophages. HCV causes persistent infections that can lead to chronic liver diseases, liver fibrosis, and hepatocellular carcinoma; the search for an HCV curative is the focus of ongoing research. Recently, effective anti-HCV drugs have been developed; however, vaccine development still is required for the prevention and therapy of infection by this virus. We demonstrate here that M2 macrophages are important for the pathogenesis of HCV-caused liver diseases and additionally show that M2 macrophages contribute to the therapeutic mechanism observed following rVV-N25 treatment.


Encouraging alternatives to seclusion, restraint, and reliance on PRN drugs in a public psychiatric hospital.
Reliance on seclusion, restraint, and psychotropic PRN (as needed) medication for behavior management has been tied to a variety of untoward outcomes that detract from the quality of care in public psychiatric hospitals. A large body of evidence has accumulated to demonstrate that behavioral approaches to care can provide useful alternatives to reliance on seclusion, restraint, and psychotropic PRN medications. This article draws from the research to outline how behavioral approaches to psychiatric care can assist in realizing alternatives to these restrictive interventions. Strategies to assess the behavioral competence of direct care staff, improve it, and establish ward programmatic structures that facilitate competent behavioral applications are discussed as well as methods to enable expert consultation and demonstrate clinical and administrative support. These steps have had a positive impact in reducing reliance on seclusion, restraint and psychotropic PRN medication in the inpatient psychiatric setting. Given the wealth of supportive data to confirm the value of behavioral applications, there is no excuse for failing to aggressively pursue these options.


Differential inhibition of human colon cancer cells by structurally similar flavonoids of citrus.
A number of studies in the recent years have evaluated the anti-proliferative activity of flavonoids. Although certain studies investigated the structure-activity based on the phenotypic assays, no study has correlated the flavonoids structure with the ability to alter gene/protein expression. Present study was focused to understand the structure-function relationship of citrus flavonoids in terms of their ability to alter the gene expression in the colon adenocarcinoma cells. Eight structurally related flavonoids found in citrus were evaluated for their ability to inhibit colon cancer (SW480) cells, as well as change the expression of apoptosis related genes/proteins. Apigenin and quercetagetin demonstrated most significant inhibition of cell proliferation with 63.6% and 45.7% inhibition of cell growth at 200μM after 48h of incubation, respectively. The cell death was also confirmed by images of fluorescently tagged cells. Furthermore, up-regulation of Bax/Bcl2 protein ratio as well as activation of Caspase3 at 200μM at 48h confirmed the induction of apoptosis by apigenin and quercetagetin. In addition, results suggest that the change in Bax/Bcl2 ratio by apigenin and quercetagetin seems to be due to their ability to alter the expression of bax and bcl2 transcription. Results of the currents study suggest that among the citrus flavonoids, double bond between C2 and C3 and hydroxyl group at C3, C6 are highly decisive for the proliferation inhibition and apoptosis induction ability. Taken together, these results demonstrate that among the major flavonoids of citrus, apigenin and quercetagetin have potent anti-cancer activity through inducing apoptosis in SW480 human colon cancer cells.


Long-term Recall of Time to Pregnancy.
Despite the widespread use of retrospectively reported time to pregnancy to evaluate fertility either as an outcome or as a risk factor for chronic disease, only two small studies have directly compared prospective data with later recall. The North Carolina Early Pregnancy Study (1982-1986) collected prospective time-to-pregnancy data from the beginning of participants' pregnancy attempt. In 2010, (24-28 years later) women were sent a questionnaire including lifetime reproductive history that asked about all prior times to pregnancy. Of the 202 women with prospective time-to-pregnancy data, 76% provided recalled time to pregnancy. A lower proportion of women with times to pregnancy ≥3 cycles provided a recalled time to pregnancy than women with times to pregnancy <3 cycles. Also, high gravidity or parity was associated with a lower likelihood of providing a recalled time to pregnancy. Women with very short or very long times to pregnancy (1 cycle or ≥13 cycles) had good recall of time to pregnancy. Positive predictive values of 1 or ≥13 cycles were 73% and 68%, respectively, while positive predictive values for other categories of time to pregnancy ranged from 38% to 58%. The weighted kappa statistic for recalled versus prospective time to pregnancy was 0.72 (95% confidence interval: 0.65, 0.79). Recalled time to pregnancy showed good agreement with prospective time to pregnancy. Informative missingness must be considered when imputing recalled time to pregnancy. Associations observed in future studies can be corrected for misclassification.


Morphological and molecular identification of four new resupinate species of Perenniporia (Polyporales) from southern China.
Four new resupinate species, Perenniporia hainaniana, P. macropora, P. russeimarginata and P. subtephropora, are described as new from southern China on the basis of morphological and molecular examination. Perenniporia hainaniana is characterized by a perennial growth habit, cream to buff pore surface, a dimitic to trimitic hyphal system with amyloid skeletal hyphae and presence of dendrohyphidia. Perenniporia macropora is distinguished by an annual growth habit, large pores (2-3 per mm), a dimitic hyphal system with branched skeletal hyphae and presence of dendrohyphidia. Perenniporia russeimarginata differs from other species in the genus by a perennial growth habit, white to cream pore surface and reddish to reddish brown sterile margin. Perenniporia subtephropora is characterized by a perennial growth habit, cream-buff to grayish buff pore surface, hymenophoral trama becoming black in KOH and a dimitic hyphal system with branched skeletal hyphae. Phylogenetic analysis inferred from the ITS and LSU-rDNA regions revealed eight clades for Perenniporia sensu lato with the four new species recognized in Perenniporia sensu stricto. The Perenniporia ochroleuca group, P. vicina group, P. martia group, P. subacida, Microporellus, Perenniporiella and Abundisporus, formed monophyletic entities respectively, and they are not related to P. medulla-panis (generic type), which belongs to Perenniporia sensu stricto. Abundisporus, Microporellus and Perenniporiella were widely applied as generic names. Other generic or clade names, Hornodermoporus, Truncospora, Vanderbylia and the P. subacida clade, have not been widely applied, but they are valid higher level taxa containing former species of Perenniporia. A key to genera and clades allied with Perennioporia sensu stricto and a key to species of Perennioporia are provided.


An emergency medical care facility: program characteristics and patient attributes.
The objectives of this research were: (1) to describe the programmatic structure and characteristics of an emergency medical care facility that is a satellite clinic of a community hospital; (2) to describe the types of illness treated, and (3) to characterize the patients who used the facility. One-half of the presenting patients were treated for traumatic conditions; a major factor of clinic use for such patients was proximity. For patients with nontraumatic illnesses, the clinic was used when private physicians were unavailable. Almost 20% of all presentations resulted from referrals, suggesting acceptance of the clinic by private practitioners in the area. Previous users had more tenuous relationships with private physicians than did initial users and no difference was found between initial and previous users in the amount of nontraumatic illness. Patient attributes of high mobility, lower socio-economic status, and younger age were associated positively with frequent clinic use.


Cellular signaling in cell death.
Apoptosis is a process of selective cell deletion involving endogenous endonuclease activation that mediates most examples of programmed cell death. Recent work has demonstrated that the process is regulated within the dying cell by signal transduction pathways, including increases in cytosolic ionized calcium concentrations, activation of protein kinases A and C, and stimulation of the nuclear enzyme poly(adenosine 5'-diphosphate-ribose) polymerase. In addition, oncogenes, tumor suppressor genes, and transcription factors also regulate induction of cell death. Evidence also indicates that apoptosis mediates a number of instances of pathologic cell death and, in some of these examples, the biochemical mechanisms responsible appear to mimic the cell-signaling mechanisms controlling the process in physiologic situations.


The combination of insulin and metformin in treatment of non-insulin-dependent diabetes mellitus.
To assess whether, in the treatment of non-insulin-dependent diabetes mellitus (NIDDM), (1) metformin in conjunction with insulin can safely cause a decrease in glycosylated hemoglobin (HbA1c) to 7% or less and (2) this combination therapy may result in weight loss and lower insulin dose in comparison with insulin treatment alone. Forty patients with NIDDM being treated with insulin on their first visit to the Diabetes Center were identified by retrospective review of medical records of all patients encountered during a 1-year period. These patients were classified into groups who were receiving insulin only (group 1) or insulin + metformin (group 2) at the most recent visit. Group 2 was subdivided into those with a body mass index of either =30 kg/m 2 (group 2A) or >30 kg/m 2 (group 2B). Blood glucose, HbA1c, insulin dose, and weights were analyzed from their initial and most recent visits. HbA1c decreased from 10 +/- 2.7% to 7 +/- 1.1% (P<0.01) in group 1 and from 9.8 +/- 2.1% to 7.2 +/- 1.4% (P<0.01) in group 2. The magnitude of decrease in HbA1c, however, was not different between the two groups. Total insulin dose increased from 40 (33 to 50) U/day to 58 (41 to 67) U/day (P<0.05) in group 1 and from 63 (42 to 118) U/day to 67 (50 to 96) U/day in group 2 (not significantly different). The median increase in insulin dose was 8 U in group 1, whereas the median decrease was 3 U in group 2 (P<0.05). Similar decreases were noted in group 2A. The decrease in insulin dose was inversely related to the initial insulin dose per kilogram of body weight in group 2 (r = -0.5; P<0.01). Patients in group 1 had an increase in weight from 75.0 +/- 8.6 kg to 77.7 +/- 9.0 kg (P<0.01), whereas weight decreased from 100.4 +/- 24.2 kg to 98.5 +/- 22.3 kg in group 2 (P<0.05). A decrease in weight was seen even in group 2A. The increase in weight was 3 +/- 3.3 kg in group 1, whereas weight decreased by 1.9 +/- 3.9 kg in group 2 (P<0.01). Insulin + metformin is safe and is as effective as insulin alone in improving glycemic control in obese and nonobese patients with NIDDM. This combination therapy, however, lowers insulin dose and promotes weight loss, which may be of importance in decreasing the cardiovascular risk factors in these subjects.