Prognostic value of selected risk scales in patients with end-stage heart failure.
Due to the increasing number of patients placed on waiting lists for orthotopic heart transplantation (OHT), the selection of patients with the highest risk of death has become paramount. This study aimed to evaluate the predictive value of the Model for End-stage Liver Disease eXcluding INR (MELD-XI) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) scales in ambulatory patients awaiting OHT and compare them to the Heart Failure Survival Score (HFSS). The study was a retrospective review of 370 adult ambulatory patients with end-stage heart failure, who were added to the OHT waiting list at our institution between 2012 and 2016. The median age of the patients was 54.0 (46.0-60.0) years, and 324 (87.6%) of them were male. The overall one-year mortality was 27.6%. The areas under the curve (AUCs) for the MAGGIC and HFSS scales were comparable: 0.771 (95% confidence interval [CI] 0.720-0.823); sensitivity 77%, specificity 68% vs. 0.781 (95% CI 0.732-0.829); sensitivity 90%, specificity 58%, respectively. The AUC for the MELD-XI scale was higher than that for the HFSS scale: 0.812 (95% CI 0.769-0.856); sensitivity 91%, specificity 63% vs. 0.781 (95% CI 0.732-0.829) sensitivity 90%, specificity 58%, respectively. Our study demonstrated that elevated MELD-XI and MAGGIC scores and lowered HFSS scores were associated with an increased risk of death during one-year follow-up. The prognostic utility of the MELD-XI scoring system was better than that of the HFSS scale, while the MAGGIC scale was comparable to the HFSS.


A method for in vitro mapping of ultrasonic speed and density in breast tissue.
A method has been developed for mapping density and ultrasonic speed in 1 mm thick slices of soft tissue with a resolution of about 1 mm. Tests using phantom sections have verified the accuracy and resolution of the ultrasonic speed maps. The method has been applied to breast tissues of three patients including tumors and surrounding tissue. Fixing a specimen in 5% formaldehyde did not change the degree of local variation in ultrasonic speeds, and raised mean speeds by less than 0.8%. The densities with fixing remained almost unchanged at low tissue densities (0.93 g/cm3), but rose 1.5% for higher tissue density (greater than 1.00 g/cm3).


Helminth Infection of the Loggerhead Sea Turtle Caretta caretta along the Coasts of Sicily and the North West Adriatic Sea.
We provide new data on the presence of helminth parasites in 64 individual loggerhead sea turtles Caretta caretta stranded along the coasts of Sicily and the northwest Adriatic Sea between June 2014 and August 2016. The necropsy examination revealed 31 individuals (48.4%) positive for endoparasites, showing a greater prevalence of trematodes than nematodes. In particular, seven species and a single genus of Trematoda (Hapalotrema) and a single species and genus of Nematoda (Kathlania) were identified. Among the Digenea flukes the species with the highest prevalence of infection were Rhytidodes gelatinosus (34.6%) and Hapalotrema sp. (33.3%), while among the Nematoda they were Kathlania sp. (33.3%) and Sulcascaris sulcata (33.3%). Analysis of variance (ANOVA) was applied among the recovery sites of the stranded loggerhead sea turtles and prevalence of endoparasites was used to highlight any relationship between the parasites and the origin of the hosts. ANOVA showed significant differences (p < 0.001) among the data used.


[Democracy and science advice: the case of environmental health risks].
Science advice, in the context of environmental health, is an activity consisting in bringing together and evaluating available scientific data at a given moment on a particular question or concern regarding the hazardous nature of an agent or substance--whether it be of a physical, chemical or microbiological nature. Science advice also relates to assessing health risks linked to the quality of the environment, in vue of rendering this information useful to those in charge of decision making and risk management. Naturally, many groups are interested by a potential hazard or risk, and they all would like to effectively intervene over the course of the process in order to influence the decision or measure taken. In this article, the author recalls that risk is an entity which is both scientific and political by nature. Hence, this demand is well founded. Nevertheless, he proposes and explicates a series of different steps, whether concurrent or successive, throughout the entire process of science advice in support of decision-making on matters related to environmental risk. He justifies why hazard and risk assessment, followed by risk analysis, requisites a clear delineation of the roles of the various actors so that their own responsibilities could be clearly attributed. The "procedural" approach of science advice, which is more and more frequently implemented within international expert groups in the international arena, satisfactorily achieves the target of objectivity, transparency and accountability.


Major haemorrhage following vascular injury during exchange of cardiac pacemaker leads.
An 80-year-old lady suffered loss of cardiac output during an elective pacemaker lead exchange. Right ventricular perforation, cardiac tamponade, vascular lacerations and circulatory shock are known major complications of pacemaker lead exchange and may necessitate aggressive resuscitation. An emergency sternotomy revealed the administered fluid, blood products and resuscitative drugs, which were administered through an upper limb cannula, had likely extravasated at the site of an iatrogenic injury to the superior vena cava. Unfortunately, further resuscitation attempts were unsuccessful. There are no recommendations regarding sites for intravascular access during pacemaker lead exchange and we argue that lower limb veins should be considered for venous access, as the superior vena cava and innominate veins are possible sites of unintentional vascular injury.


Fetal interlens distance: normal values during pregnancy.
The aims of this study were to establish normal ranges of values for interlens distance (ILD) during gestation, and to assess the correlation between ILD and growth of the orbits and other fetal biometric parameters. A cross-sectional study of morphologically normal, singleton fetuses was carried out in low-risk pregnant women. We measured the distance between the centers of the fetal lenses from 12 to 37 completed weeks of gestation. An oblique anterior coronal section was used to measure the ILD. The biorbital diameter (BOD) was measured in the same plane. We analyzed the correlation between the ILD and gestational age (GA), BOD, biparietal diameter (BPD), head circumference (HC), femur length (FL) and abdominal circumference (AC). Fetal gender was assessed to evaluate possible significant differences. Four hundred and fifty normal fetuses were recruited for the study. In 427 fetuses appropriate ILD measurements were obtained, and complete evaluation of all parameters was accomplished in 377 of these. ILD demonstrated a high positive correlation with GA (r(2) = 0.969), BPD (r(2) = 0.959), HC (r(2) = 0.962), AC (r(2) = 0.949) and FL (r(2) = 0.956) as pregnancy advanced. The mean BOD : ILD ratio was 1.50 +/- 0.08, remaining constant throughout pregnancy (linear regression r(2) = 0.006). No statistically significant differences were found between genders for mean ILD and GA of the study population (P = 0.604 and 0.595, respectively). The results of this study confirm previous hypotheses regarding the close relationship between eyeball growth and growth of the surrounding bony structures. Measurement of fetal ILD, which can be used interchangeably with BOD measurement in either the axial or coronal plane, can be taken to reflect the expected development of the fetal orbits whilst simultaneously providing valuable information on eyeball development. It is likely that ILD could be used as a complementary tool in the elaboration of various severe abnormalities, mainly related to craniofacial and nervous system malformations.


Fabrication of ordered mesoporous thin films for optical waveguiding and interferometric chemical sensing.
Planar optical waveguides with a propagation loss of 2.9 dB/cm at 633 nm were fabricated using ordered mesoporous thin films of TiO2-P2O5 nanocomposite deposited on the tin-rich surfaces of float glass slides. The resulting waveguides show substantial sensitivity to parts-per-million-level ammonia gas at room temperature on the basis of single-beam polarimetric interferometry.


Fas mediates apoptosis and oxidant-induced cell death in cultured hRPE cells.
To investigate whether Fas ligand (FasL) and the Fas receptor system mediates apoptosis in cultured human retinal pigment epithelial (hRPE) cells and contributes to oxidant-induced death of hRPE cells. Expression of FasL and Fas in cultured hRPE cells was examined by Western blot analysis and flow cytometry. The susceptibility of hRPE cells to Fas-mediated apoptosis was determined by incubating cells with recombinant soluble Fas ligand (sFasL). Characteristics of apoptosis assessed included chromatin condensation, DNA cleavage, and phosphatidylserine exposure. To investigate the possible involvement of Fas-mediated apoptosis in oxidative killing of hRPE cells, the effects of the oxidant tert-butylhydroperoxide (tBH) on the expression of FasL and Fas were studied. The specificity of effects of oxidant was examined using the antioxidants glutathione and N-acetyl-L-cysteine (NAC). The requirement for the Fas pathway in tBH-induced apoptosis was investigated using an antagonistic anti-Fas antibody ZB4 that blocks the interaction between FasL and Fas. Cultured hRPE cells constitutively expressed FasL and Fas. Ligation of Fas receptor with recombinant sFasL triggered apoptosis in hRPE cells. tBH treatment of hRPE cells resulted in increased expression of FasL and Fas. Glutathione and NAC completely abrogated tBH-induced increase in FasL and Fas expression and apoptosis. Blocking FasL and Fas interaction by ZB4 inhibited tBH-induced apoptosis, but only partially. A functional Fas-mediated apoptotic pathway is present in cultured hRPE cells and can be activated with sFasL or by upregulation of FasL and Fas expression with an oxidant. The incomplete inhibition by blocking antibody indicates that the Fas pathway is involved in oxidant-induced apoptosis, but other triggering mechanisms are also important.


[Mild psychosomatic illnesses].
Referring to our August article on psychosomatic illness, the author states that there are harmless forms of this disorder that nearly everyone, including nurses, experience at some point in their lives. Early awareness is an important step toward defusing potentially harmful psychosomatic problems.


Epigenetic remodeling in B-cell acute lymphoblastic leukemia occurs in two tracks and employs embryonic stem cell-like signatures.
We investigated DNA methylomes of pediatric B-cell acute lymphoblastic leukemias (B-ALLs) using whole-genome bisulfite sequencing and high-definition microarrays, along with RNA expression profiles. Epigenetic alteration of B-ALLs occurred in two tracks: de novo methylation of small functional compartments and demethylation of large inter-compartmental backbones. The deviations were exaggerated in lamina-associated domains, with differences corresponding to methylation clusters and/or cytogenetic groups. Our data also suggested a pivotal role of polycomb and CTBP2 in de novo methylation, which may be traced back to bivalency status of embryonic stem cells. Driven by these potent epigenetic modulations, suppression of polycomb target genes was observed along with disruption of developmental fate and cell cycle and mismatch repair pathways and altered activities of key upstream regulators.


Metazoans and Intrinsic Apoptosis: An Evolutionary Analysis of the Bcl-2 Family.
The B-cell lymphoma-2 (Bcl-2) family is a group of genes regulating intrinsic apoptosis, a process controlling events such as development, homeostasis and the innate and adaptive immune responses in metazoans. In higher organisms, Bcl-2 proteins coordinate intrinsic apoptosis through their regulation of the integrity of the mitochondrial outer membrane; this function appears to have originated in the basal metazoans. Bcl-2 genes predate the cnidarian-bilaterian split and have been identified in porifera, placozoans and cnidarians but not ctenophores and some nematodes. The Bcl-2 family is composed of two groups of proteins, one with an α-helical Bcl-2 fold that has been identified in porifera, placozoans, cnidarians, and almost all higher bilaterians. The second group of proteins, the BH3-only group, has little sequence conservation and less well-defined structures and is found in cnidarians and most bilaterians, but not porifera or placozoans. Here we examine the evolutionary relationships between Bcl-2 proteins. We show that the structures of the Bcl-2-fold proteins are highly conserved over evolutionary time. Some metazoans such as the urochordate Oikopleura dioica have lost all Bcl-2 family members. This gene loss indicates that Bcl-2 regulated apoptosis is not an absolute requirement in metazoans, a finding mirrored in recent gene deletion studies in mice. Sequence analysis suggests that at least some Bcl-2 proteins lack the ability to bind BH3-only antagonists and therefore potentially have other non-apoptotic functions. By examining the foundations of the Bcl-2 regulated apoptosis, functional relationships may be clarified that allow us to understand the role of specific Bcl-2 proteins in evolution and disease.


Access to Opioids for Patients with Advanced Disease.
Pain at the end of life is common in both malignant and non-malignant disease. It is feared by patients, their families and careers, and professionals. Effective pain control can be achieved for the majority of patients at the end of life using a multimodal approach. Pharmacological management relies predominantly on strong opioids. In spite of this, evidence suggests that under treatment of pain is common resulting in unnecessary suffering. Multiple barriers to use of opioids have been identified. Patient barriers include reluctance to report pain and to take analgesics. Professional barriers include inadequate pain assessment and lack of specialist knowledge and confidence in opioid therapy. Fear of side effects including respiratory depression affects patients and professionals alike. The impact of the "opioid epidemic", with increasing prescribed and illicit opioid use around the world, has also led to increasingly stringent regulation and concern about under prescribing in palliative care. System barriers to use of opioids at the end of life result from limited opioid availability in some countries and also inconsistent and limited access to palliative care. Multiple interventions have been developed to address these barriers, targeted at patients, professionals and systems. There is increasing evidence to suggest that complex interventions combining a number of different approaches are most effective in optimising pain outcomes for patients at the end of life.


Practical guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline.
Patients with chronic gastrointestinal disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean gastrointestinal patients. The present guideline addresses this question according to current knowledge and evidence. The present practical guideline is intended for clinicians and practitioners in general medicine, gastroenterology, surgery and other obesity management, including dietitians and focuses on obesity care in patients with chronic gastrointestinal diseases. The present practical guideline is the shortened version of a previously published scientific guideline developed according to the standard operating procedure for ESPEN guidelines. The content has been re-structured and transformed into flow-charts that allow a quick navigation through the text. In 100 recommendations (3× A, 33× B, 24 × 0, 40× GPP, all with a consensus grade of 90% or more) care of gastrointestinal patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially metabolic associated liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. The present practical guideline offers in a condensed way evidence-based advice how to care for patients with chronic gastrointestinal diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.


Calcific tendonitis of the quadriceps tendon.
A 61-year-old woman presented with chronic anterior pain and stiffness in the distal left thigh. Examination revealed swelling and tenderness immediately proximal to the patella. Radiographs showed opacities in the distal anterior thigh whilst MRI identified enlargement of the distal quadriceps tendon with splayed fibres separated by solid conglomerates. Dystrophic calcification of the quadriceps tendon was diagnosed. Blood tests revealed no systemic abnormalities in calcium handling. Arthroscopy of the left knee identified calcific deposits in the supra-patella pouch with surrounding synovitis. An open debridement of the tendon was performed; biopsy of the excised tendon showed chronic tenosynovitis with dystrophic calcification without evidence of malignancy. Post-operatively her knee was braced in extension enabling progressive flexion over 4 weeks. Anterior knee pain diminished post-operatively and 10 months following surgery the patient was pain free, able to walk normally and scored 99/100 on the Fulkerson modification of the Lysholm score.


Photodynamic therapy for unresectable cholangiocarcinoma.
Cholangiocarcinoma (CC) is a rare primary malignancy of the biliary tract with a dismal prognosis. Curative resection can only be applied to a small proportion of early diagnosed patients. Palliative biliary drainage by either percutaneous or endoscopic insertion of endoprostheses improves quality-of-life by reducing pruritis, cholangitis, and pain, but has been reported to improve survival time only slightly. Photodynamic therapy (PDT) is a relatively new local, minimally invasive palliative strategy for unresectable CC. PDT uses a photosensitive molecule that accumulates in proliferating tissue such as tumors. Activation of the photosensitizer by use of light of a specific wavelength generates reactive oxygen species leading to selective tumor-cell death. After initial feasibility studies and promising prospective phase II studies, results from two prospective randomized controlled trials comparing PDT after endoprostheses insertion with endoprostheses alone for patients with unresectable CC have been published. One study resulted in dramatically prolonged median survival in the PDT group (493 days) compared with the non-PDT group (98 days) (P < 0.0001), and significantly improved performance status (PS) in the PDT group. A second study with high baseline patients' PS confirmed the benefit of PDT for survival (630 days in the PDT group compared with 210 days for endoprostheses alone, P < 0.01). The procedures were generally well tolerated. PDT has also been reported to have a favorable outcome as adjuvant and neoadjuvant therapy for CC. Although accumulated data and local expertise are limited, PDT can be regarded as a standard palliative therapy for unresectable CC.


Relations between program and system variables and fidelity to the wraparound process for children and families.
Past research and experience have indicated that characteristics of organizations and service systems influence the quality of mental health services delivery. The study aimed to illuminate such associations by examining the relationship between a set of program- and system-level variables and fidelity to the wraparound model for children and families. A measure of fidelity to the wraparound process for children and families (the Wraparound Fidelity Index) was administered to families receiving services in eight mental health agencies across the United States. Program administrators at each agency also completed by telephone a standardized interview for assessing program and system conditions hypothesized to influence quality of implementation (Program Administrator version of the Wraparound Fidelity Index). Regression analyses were used to assess the relationship between program and system variables and fidelity. Results of interviews with program administrators revealed substantial variation across programs in the number and type of program and system supports for wraparound implementation. Regression analyses found a significant association between the number of organizational and system supports and Wraparound Fidelity Index scores. Results support the hypothesized relationship between program and system conditions and the quality of service delivery. Results also highlight the importance of engineering the system and organizational context (maintaining low caseload sizes, establishing interagency partnerships, and implementing accountability mechanisms) in order to provide a solid foundation for high-quality wraparound to children and families.


Expression levels of FGFR3 as a prognostic marker for the progression of primary pT1 bladder cancer and its association with mutation status.
The present study examined the utility of fibroblast growth factor receptor 3 (FGFR3) mutation status and gene expression as a prognostic marker in primary pT1 bladder cancer (BC). A total of 120 patients with primary pT1 BC were enrolled. FGFR3 mutation status was determined by direct sequencing and FGFR3 mRNA expression level was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The results were compared with the clinicopathological parameters, and the prognostic value of FGFR3 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression test. FGFR3 mutations were identified in 48/120 (40.0%) patients with pT1 BC. FGFR3 mRNA expression level was significantly higher in those with BC harboring FGFR3 mutations (P<0.001). Low FGFR3 expression level was associated with high-grade tumors and cancer progression (P=0.006 and P=0.001), whereas FGFR3 mutation status was not associated with cancer progression. Kaplan-Meier analysis revealed a similar result (log-rank, P<0.001). Multivariate analysis identified low FGFR3 expression level (odds ratio, 3.300; 95% confidence interval, 1.310-8.313; P=0.011) as an independent predictor of cancer progression. Stratification by exon site of FGFR3 mutations yielded significant differences in mRNA expression level. None of the patients with BC harboring FGFR3 mutations in exon 9 demonstrated disease progression. The mRNA expression level of the FGFR3 gene may be used to precisely identify subsets of patients with pT1 BC that have a relatively better prognosis. The prognostic influences of FGFR3 mutations may be modulated by the exon site of FGFR3 mutations.


Whole-Exome Sequencing in a Cohort of High Myopia Patients in Northwest China.
High myopia (HM) is one of the leading causes of visual impairment worldwide. In order to expand the myopia gene spectrum in the Chinese population, we investigated genetic mutations in a cohort of 27 families with HM from Northwest China by using whole-exome sequencing (WES). Genetic variations were filtered using bioinformatics tools and cosegregation analysis. A total of 201 candidate mutations were detected, and 139 were cosegregated with the disease in the families. Multistep analysis revealed four missense variants in four unrelated families, including c.904C>T (p.R302C) in CSMD1, c.860G>A (p.R287H) in PARP8, c.G848A (p.G283D) in ADAMTSL1, and c.686A>G (p.H229R) in FNDC3B. These mutations were rare or absent in the Exome Aggregation Consortium (ExAC), 1000 Genomes Project, and Genome Aggregation Database (gnomAD), indicating that they are new candidate disease-causing genes. Our findings not only expand the myopia gene spectrum but also provide reference information for further genetic study of heritable HM.


Frequency of dementia, depression, and other neuropsychiatric symptoms in 1,449 outpatients with Parkinson's disease.
Neuropsychiatric symptoms (NPS) of Parkinson's disease (PD) are of growing diagnostic and therapeutic importance. Data on their prevalence and characteristics have been primarily derived from highly selective clinical populations. We have conducted a national study in the outpatient care sector to provide a fuller characterization of the frequency of dementia, depression, and other NPS in PD outpatients. We also examined associations with biosocial and neurological variables. A nationwide representative sample of 1,449 PD outpatients was examined with a standardized clinical interview. PD severity was rated with the Hoehn and Yahr (HY) scale and the Unified Parkinson's Disease Rating Scale. Depression was measured with the Montgomery-Asberg Depression Rating Scale. Cognitive impairment and dementia were assessed with the Mini-Mental State Exam and according to diagnostic criteria. Logistic regression analyses were used to investigate associations. At least one NPS occurred in 71% of all patients with PD. The estimated prevalences (ranges) by age group and HY-stage were: depression, 25% (13.2-47.9%), dementia, 29% (12.2-59.4%), and psychotic syndromes, 12.7% (3.1-40.9%). Other frequent complications were sleep disturbances (49%) and anxiety (20%). Depression was associated with gender but not with age. Dementia was associated with age. The rates and comorbidity of depression and dementia were driven by PD severity. NPS were highly prevalent in our comprehensive patient sample, largely representative of management problems occurring in an outpatient setting. PD outpatients are at an increased risk for all neuropsychiatric conditions, increasing with PD severity but not with age or age of onset (except dementia), revealing challenging symptom patterns.


Strong gastric contractions cause mucosal ischemia.
Contractions of a segment of bowel result in alterations of its blood flow. However, the precise temporal and spacial relationships between contractions and mucosal blood flow are unknown. Rats were fitted with strain gauge force transducers and implanted with silver wire electrodes into the muscularis externa of the stomach. In vivo microscopic observation of motility and of the gastric mucosal blood flow was performed during electrical field-stimulated contractions. Contractions originated in the midcorpus, were 0.237 +/- 0.018 cm wide, traveled along the corpus at 0.133 +/- 0.024 cm/s, and had a duration of 5.9 +/- 0.1 s. Antral contractions were 0.174 +/- 0.032 cm wide, traveled at 0.070 +/- 0.009 cm/s, and had a duration of 5.6 +/- 0.7 s. During the contraction, capillary flow velocity in the corpus decreased from a basal value of 410 +/- 105 to 206 +/- 104 microns/s at the peak of a contraction. Five seconds after the contraction was released hyperemia was observed with the flow velocity increasing to 570 +/- 102 microns/s. In the antrum, flow stopped completely during the contraction irrespective of the initial flow velocity and no hyperemia occurred with release of the contraction; rather, flow velocity slowly returned to baseline values. In both regions the flow reductions were in phase with the contractions as measured by the force transducers. These studies provide direct evidence that strong gastric contractions can effectively reduce or stop gastric mucosal blood flow.


A general theory of kinetics and thermodynamics of steady-state copolymerization.
Kinetics of steady-state copolymerization has been investigated since the 1940s. Irreversible terminal and penultimate models were successfully applied to a number of comonomer systems, but failed for systems where depropagation is significant. Although a general mathematical treatment of the terminal model with depropagation was established in the 1980s, a penultimate model and higher-order terminal models with depropagation have not been systematically studied, since depropagation leads to hierarchically-coupled and unclosed kinetic equations which are hard to solve analytically. In this work, we propose a truncation method to solve the steady-state kinetic equations of any-order terminal models with depropagation in a unified way, by reducing them into closed steady-state equations which give the exact solution of the original kinetic equations. Based on the steady-state equations, we also derive a general thermodynamic equality in which the Shannon entropy of the copolymer sequence is explicitly introduced as part of the free energy dissipation of the whole copolymerization system.


Cervical varicosities, an uncommon cause of third-trimester bleeding in pregnancy: A case report.
Cervical varicosities are dilated cervical veins and are uncommon causes of third-trimester vaginal bleeding. Early identification of patients with cervical varices is critical to prevent postpartum hemorrhage, which increases the risk of maternal morbidity and mortality. This is a case report of a 30-year-old woman, gravida 2 para 1, who presented to the labor and delivery unit at 35 weeks 6 days of gestation with a singleton pregnancy with vaginal bleeding. She underwent a pelvic exam under anesthesia and was found to have a 5x5 cm mass of varicosities protruding from the external cervical os, extending over the anterior vaginal lip to the anterior vaginal fornix. A decision was made to deliver via cesarean section. Intraoperative findings were significant for 800 cc of blood loss and a 5-6 cm right ovarian teratoma, which was excised. The patient received two units of packed red blood cells for acute blood-loss anemia postoperatively. This case is unique as the patient had none of the established risk factors for the development of cervical varices. Due to the risks of hemorrhage, morbidity and mortality, physicians and healthcare providers should include cervical varices in their differential diagnoses of patients who present with vaginal bleeding.


Wound-healing effect of electrospun gelatin nanofibres containing Centella asiatica extract in a rat model.
Centella asiatica (CA) is a traditional herbal medicine that has been shown to exert pharmacological effects on wound healing. This study demonstrated that CA extract facilitates the wound-repair process by promoting fibroblast proliferation and collagen synthesis and exhibits antibacterial activity. Gelatin nanofibres containing C. asiatica extract were fabricated via electrospinning and were shown to exhibit dermal wound-healing activity in a rat model. The wound areas of rat skin treated with electrospun gelatin membranes containing C. asiatica (EGC) presented the highest recovery rate compared with those treated with gauze, neat gelatin membranes and commercial wound dressings. The results of the histopathological examination support the outcome of the wound models. Contact-angle and water-retention measurements confirmed that the addition of C. asiatica extract did not significantly affect the hydrophilicity of the EGC membranes. The measured weight loss revealed that the EGC membranes are biodegradable. The findings suggest that EGC membranes are a promising material for the treatment of skin wounds. Copyright © 2015 John Wiley & Sons, Ltd.


The changing face of intussusception.
Management of intussusception in a pediatric center shows changing patterns over the past 26 years. Early and subacute cases of intussusception are now ordinarily successfully reduced by hydrostatic pressure (barium enema). A minority, who are in shock, who have evidence of significant blood loss or, in whom small intestinal obstruction is apparent, are treated by emergency laparotomy, with or without confirmatory contrast studies. In the latter group the rate of resection is high (16.4% in the present series). Resected segments are microscopically infarcted; with unnecessary resection a rarity. Advances in surgical management have eliminated a major portion of the mortality formerly associated with resection. The use of hydrostatic pressure reduction makes surgery unnecessary in a high percentage of infants with intussusception, but does not reduce the incidence of infarction requiring resection. Ambulatory or nonhospital management of intussusception subjects the infant to the risk of a significant delay in definitive treatment and is not to be condoned.


Optimization of a new non-viral vector for transfection: Eudragit nanoparticles for the delivery of a DNA plasmid.
The development of new vectors to deliver DNA into cells for therapy of cancers or genetic diseases has been a major area of research for many years. However, the clinical application of this technology requires the development of efficient, reliable and sterile vectors enabling the transfer of genes in vivo. Non viral, polymer or lipid-based vectors offer a new impetus to gene therapy because they are less toxic than viral vectors (no endogenous recombination, fewer immunological reactions, easy production and delivery of large-sized plasmid). The aim of this study is to develop a new tool for DNA delivery composed of methacrylic polymeric (Eudragit RS and RL) nanoparticles. These nanoparticles were prepared by two methods: nanoprecipitation and double emulsion. The nanoparticles were characterized by their size, zeta potential and amount of DNA adsorption. Cytotoxicity tests based on mitochondrial activity (MTT test) revealed that the nanoparticles had limited cytotoxicity and that this depended on both the cell type and the nanoparticle concentration. Transgene expression was observed using the Green Fluorescence Protein gene as reporter gene, and was evaluated by flow cytometry in FaDu, MDA-MB 231 and MCF-7 cell lines. The results showed that transfection rates ranging between 4 and 7% were achieved in FaDu and MDA-MB 231 cells with nanoparticles prepared by the nanoprecipitation method. In MCF-7 cells transfected with nanoparticles prepared by either the double emulsion or the nanoprecipitation method, the transfection efficiency was between 2 and 4%. Nanoparticles prepared by nanoprecipitation were slightly more efficient than nanoparticles prepared from a double emulsion. Particle size was not an important factor for transfection, since no significant difference was observed with size between 50 and 350 nm. We showed that Eudragit RS and RL nanoparticles could introduce the transgene into different types of cells, but were generally less effective than the lipofectamine control.


Effect of interferon alpha and ribavirin treatment on serum levels of transforming growth factor-beta1, vascular endothelial growth factor, and basic fibroblast growth factor in patients with chronic hepatitis C.
To assess the role of transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the pathogenesis of fibrosis associated with chronic hepatitis C (CHC) and to evaluate the influence of the antiviral therapy on above parameter levels depending on the treatment results (complete response or no response). Study group included 100 patients with CHC, in whom fibrosis in liver specimens was assessed (Scheuer fibrosis score: 1-4 points). Control group included 30 subjects with antibodies anti-HCV present and persistently normal ALT level, without fibrosis (Scheuer fibrosis score: 0 points). Concentration of studied parameters was assayed in the serum by immunoenzymatic method before and after the therapy with interferon alpha-2b and ribavirin. TGF-beta1 levels were significantly higher in the study group compared to the control group (35.89 vs 32.37 ng/mL; P=0.023). Such differences were not found in VEGF and bFGF levels. In patients showing complete response (negative HCV RNA and normal ALT level), significant increase in VEGF (112.8 vs 315.03 pg/mL; P<0.05) and bFGF (2.51 vs 15.79 pg/mL; P=0.04) levels were found. Significant decrease in TGF-beta1 level was observed both in responders (37.44 vs 30.02 ng/mL; P=0.05), and in non-responders (38.22 vs 30.43 ng/mL; P=0.043). bFGF levels before the treatment were significantly lower (2.51 vs 5.94 pg/mL; P=0.04), and after the treatment significantly higher (15.79 vs 4.35 pg/mL; P=0.01) in patients with complete response than in those with no response. Among the analyzed parameters TGF-beta1 seems to play the most important role in the pathogenesis of fibrosis in CHC. Levels of this factor are significantly lower in subjects who do not have fibrosis developed in them. Good therapeutic effect in CHC patients is associated with significant changes in TGF-beta1, VEGF, and bFGF levels. bFGF seems to have the highest usefulness in the prognosis of treatment efficacy.


[Onchocerciasis].
Onchocerciasis, which is caused by filarial nematodes, affects roughly 18 million people in tropical Africa and is a major cause of morbidity, with a serious sociomedical impact. Although the present onchocerciasis control strategy comprising antifilarial chemotherapy and vector control is successful, it is associated with logistic problems due to the prolonged treatment duration. Furthermore, fears of drug resistance are on the increase. New approaches involving the use of antibiotics aimed at endobacteria living in symbiosis with filariae appear promising. Recent trials with tetracycline indicate a significant impact on worm viability.


[Landform-based pedodiversity of some soil chemical properties in Hainan Island, China].
Diversity indices and abundance distribution models are the statistical tools having been applied by ecologists for decades to analyze the intrinsic regularities of various ecological entities. In this work, similar techniques were used to analyze the pedodiversity of some soil chemical properties in Hainan Island, China, and discussions were conducted on the basis of related SOTER digital databases. Through the calculation of the richness (S), diversity (H') and evenness (E) of pH value, CEC and organic matter content in surface soil of different landforms and the establishment and application of the multi-distribution models of these soil chemical properties, the pedodiversity of some soil chemical properties of different landforms in Hainan Island in the GIS environment could be expressed digitally.


[Masticatory pattern of patients with TMJ clicking].
36 patients with clicking of the TMJ during chewing were examined to determine the influence of clicking sounds on masticatory performance. Electrognathographic measurements of chewing movements in the sagittal plane were compared with the electronic records of clicking sounds. Four characteristic features of chewing movements associated with the incidence of clicking sounds could be identified.


Waterborne disease in Norway: emphasizing outbreaks in groundwater systems.
In this study, we compiled and examined available data on waterborne disease outbreaks (1984-2007) in Norway, with emphasis on groundwater systems. A total of 102 waterborne outbreaks and 17,243 disease cases were reported during the period 1984-2007. The proportion of outbreaks related to groundwater reflected the proportion of groundwater works in Norway (40%). The proportion of disease cases corresponded to the proportion of persons supplied by groundwater (15%). Norovirus was identified as the most important disease causing agent in groundwater systems. No clear seasonal correlation was observed for Norovirus outbreaks in groundwater, but the largest outbreaks occurred during winter season. All outbreaks of campylobacteriosis occurred during March to November, with a peak in July-September, which correlates with the occurrence of coliforms in Norwegian groundwater in bedrock wells.


Reduction in risk-taking behaviors among MSM in Senegal between 2004 and 2007 and prevalence of HIV and other STIs. ELIHoS Project, ANRS 12139.
An epidemiological survey conducted in Senegal in 2004 among men having sex with men (MSM) revealed high HIV prevalence and a high rate of risky behaviors within this population. Consequently, several prevention campaigns targeting MSM were implemented. A second survey was carried out in 2007 to assess the impact of these measures. This paper aims to examine trends in HIV and STI prevalence and in sexual behaviors between 2004 and 2007. The two surveys were conducted in four urban sites among 440 and 501 MSM--recruited using the snowball sampling method--in 2004 and 2007, respectively. A similar methodology was applied for both surveys. This consisted of a closed-ended questionnaire concerning socio-demographic, behavioral, and biomedical information plus a clinical examination including urine and blood tests to detect STIs and HIV infection. Between 2004 and 2007, the frequency of different sexual practices reported by MSM remained stable, but condom use for each type of sexual practice rose. The percentage of men who reported consistent condom use during previous-month anal sex has increased by about 35% (p<0.01). The percentage of men who reported consistent condom use during previous-month non-commercial sex with women has increased by 14% (p<0.01). HIV prevalence remained stable from 22.4% [95% CI: 18.6-26.8] in 2004 to 21.8% [95% CI: 18.3-25.7] in 2007 (adjusted OR = 1.05, p=0.8). Gonorrhea prevalence decreased from 5.5% [95% CI: 3.6-8.3] in 2004 to 2.6% [95% CI: 1.5-4.5] in 2007 (adjusted OR=0.5, p=0.07). The prevention campaigns, STI and HIV care and support programs conducted in Senegal among MSM have been followed by a reduction of risk-taking behaviors and STI prevalence among this population. Specific targeting of this group within HIV/STI prevention programs seems to be effective in decreasing sexual infections.


Scaffold Pore Geometry Guides Gene Regulation and Bone-like Tissue Formation in Dynamic Cultures.
Cells sense and respond to scaffold pore geometry and mechanical stimuli. Many fabrication methods used in bone tissue engineering render structures with poorly controlled pore geometries. Given that cell-scaffold interactions are complex, drawing a conclusion on how cells sense and respond to uncontrolled scaffold features under mechanical loading is difficult. In this study, monodisperse templated scaffolds (MTSC) were fabricated and used as well-defined porous scaffolds to study the effect of dynamic culture conditions on bone-like tissue formation. Human bone marrow-derived stromal cells were cultured on MTSC or conventional salt-leached scaffolds (SLSC) for up to 7 weeks, either under static or dynamic conditions (wall shear stress [WSS] using spinner flask bioreactors). The influence of controlled spherical pore geometry of MTSC subjected to static or dynamic conditions on osteoblast cell differentiation, bone-like tissue formation, structure, and distribution was investigated. WSS generated within the two idealized geometrical scaffold features was assessed. Distinct response to fluid flow in osteoblast cell differentiation were shown to be dependent on scaffold pore geometry. As revealed by collagen staining and microcomputed tomography images, dynamic conditions promoted a more regular extracellular matrix (ECM) formation and mineral distribution in both scaffold types compared with static conditions. The results showed that regulation of bone-related genes and the amount and the structure of mineralized ECM were dependent on scaffold pore geometry and the mechanical cues provided by the two different culture conditions. Under dynamic conditions, SLSC favored osteoblast cell differentiation and ECM formation, whereas MTSC enhanced ECM mineralization. The spherical pore shape in MTSC supported a more trabecular bone-like structure under dynamic conditions compared with MTSC statically cultured or to SLSC under either static or dynamic conditions. These results suggest that cell activity and bone-like tissue formation is driven not only by the pore geometry but also by the mechanical environment. This should be taken into account in the future design of complex scaffolds, which should favor cell differentiation while guiding the formation, structure, and distribution of the engineered bone tissue. This could help to mimic the anatomical complexity of the bone tissue structure and to adapt to each bone defect needs. Impact statement Aging of the human population leads to an increasing need for medical implants with high success rate. We provide evidence that cell activity and the amount and structure of bone-like tissue formation is dependent on the scaffold pore geometry and on the mechanical environment. Fabrication of complex scaffolds comprising concave and planar pore geometries might represent a promising direction toward the tunability and mimicry the structural complexity of the bone tissue. Moreover, the use of fabrication methods that allow a systematic fabrication of reproducible and geometrically controlled structures would simplify scaffold design optimization.


Brassinosteroids inhibit pathogen-associated molecular pattern-triggered immune signaling independent of the receptor kinase BAK1.
Plants and animals use innate immunity as a first defense against pathogens, a costly yet necessary tradeoff between growth and immunity. In Arabidopsis, the regulatory leucine-rich repeat receptor-like kinase (LRR-RLK) BAK1 combines with the LRR-RLKs FLS2 and EFR in pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and the LRR-RLK BRI1 in brassinosteroid (BR)-mediated growth. Therefore, a potential tradeoff between these pathways mediated by BAK1 is often postulated. Here, we show a unidirectional inhibition of FLS2-mediated immune signaling by BR perception. Unexpectedly, this effect occurred downstream or independently of complex formation with BAK1 and associated downstream phosphorylation. Thus, BAK1 is not rate-limiting in these pathways. BRs also inhibited signaling triggered by the BAK1-independent recognition of the fungal PAMP chitin. Our results suggest a general mechanism operative in plants in which BR-mediated growth directly antagonizes innate immune signaling.


Isolation and cultivation of equine corneal keratocytes, fibroblasts and myofibroblasts.
To establish an in vitro model for the investigation of equine corneal wound healing. To accomplish this goal, a protocol to isolate and culture equine corneal keratocytes, fibroblasts and myofibroblasts was developed. ANIMAL MATERIAL: Equine corneal buttons were aseptically harvested from healthy research horses undergoing humane euthanasia for reasons unrelated to this study. Slit-lamp biomicroscopy was performed prior to euthanasia by a board-certified veterinary ophthalmologist to ensure that all samples were harvested from horses free of anterior segment disease. Equine corneal stroma was isolated using mechanical techniques and stromal sub-sections were then cultured. Customized media at different culture conditions was used to promote growth and differentiation of corneal stromal cells into keratocytes, fibroblasts and myofibroblasts. Cell culture techniques were successfully used to establish a method for the isolation and culture of equine corneal keratocytes, fibroblasts and myofibroblasts. Immunohistochemical staining for alpha-smooth muscle and F-actin was used to definitively differentiate the three cell types. Equine corneal stromal keratocytes, fibroblasts and myofibroblasts can be predictably isolated and cultured in vitro using this protocol.


Preparation and Characterization of Magnetic Metal-Organic Frameworks Functionalized by Ionic Liquid as Supports for Immobilization of Pancreatic Lipase.
Enzymes are difficult to recycle, which limits their large-scale industrial applications. In this work, an ionic liquid-modified magnetic metal-organic framework composite, IL-Fe3O4@UiO-66-NH2, was prepared and used as a support for enzyme immobilization. The properties of the support were characterized with X-ray powder diffraction (XRD), Fourier-transform infrared (FTIR) spectra, transmission electron microscopy (TEM), scanning electronic microscopy (SEM), and so on. The catalytic performance of the immobilized enzyme was also investigated in the hydrolysis reaction of glyceryl triacetate. Compared with soluble porcine pancreatic lipase (PPL), immobilized lipase (PPL-IL-Fe3O4@UiO-66-NH2) had greater catalytic activity under reaction conditions. It also showed better thermal stability and anti-denaturant properties. The specific activity of PPL-IL-Fe3O4@UiO-66-NH2 was 2.3 times higher than that of soluble PPL. After 10 repeated catalytic cycles, the residual activity of PPL-IL-Fe3O4@UiO-66-NH2 reached 74.4%, which was higher than that of PPL-Fe3O4@UiO-66-NH2 (62.3%). In addition, kinetic parameter tests revealed that PPL-IL-Fe3O4@UiO-66-NH2 had a stronger affinity to the substrate and, thus, exhibited higher catalytic efficiency. The results demonstrated that Fe3O4@UiO-66-NH2 modified by ionic liquids has great potential for immobilized enzymes.


Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.
An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells.


Adolescents' experiences of a theory-based behavioural intervention for improved oral hygiene: A qualitative interview study.
Adequate oral hygiene, that is self-performed infection control, is crucial to prevent periodontal disease. Epidemiological studies reveal poor oral hygiene conditions among Swedish adolescents and indicate a need for more effective prevention programs. The aim of the current study was to analyse adolescents' experiences of a person-centred, theory-based, oral health education program for improved oral hygiene. Data were obtained by interviewing 19 adolescents treated by dental hygienists in accord with the person-centred education program in a preceding clinical field study (ClinicalTrials.gov NCT02906098). Study participants were selected to reflect a variation of male and female adolescents, treated at clinics in areas with various socio-demographic profiles within Region Västra Götaland, Sweden. Interviews were audio-taped, transcribed verbatim and analysed with qualitative content analysis. A main theme was identified: 'Adolescents on a guided and challenging journey towards beneficial oral hygiene behavior'. The results elucidate the importance of a person-centred approach in therapy. The adolescents described insight on a personal level about the importance of improved oral hygiene as fundamental for behavioural change. Planning and monitoring of the behaviour, with guidance and support by the dental hygienist, was considered to facilitate change and encouraged further behavioural efforts. However, the adolescents expressed a need of reminders and support to keep up oral hygiene routines over time. The study brings knowledge on factors of importance in educational interventions to increase beneficial health behaviours among adolescents and emphasize areas for further improvements of such interventions.


Analysis of the volatile compounds of Teucrium flavum L. subsp. flavum (Lamiaceae) by headspace solid-phase microextraction coupled to gas chromatography with flame ionisation and mass spectrometric detection.
In this study, a headspace solid-phase microextraction (HS-SPME) method, in combination with gas chromatography flame ionisation detector and gas chromatography-mass spectrometry, has been developed for use in the analysis of the volatile compounds of Teucrium flavum L. subsp. flavum, a plant whose particular fragrance is used in the preparation of flavoured wines, bitters and liqueurs, or as a substitute for hops in the flavouring of beer. The tested fibres were 100 µm poly(dimethylsiloxane) (PDMS), the 65 µm PDMS/divinylbenzene (DVB) and 50/30 µm DVB-carboxen-PDMS. The best fibre was found to be PDMS when working in the following conditions: 60°C temperature, 30 min extraction time, 30 mg sample amount, 1 mm sample particle size. The HS-SPME method permitted the identification (95.8-97.8%) of 76 (dry) and 66 (fresh) different volatiles. In addition, we discovered that the presence of water in the sample can enhance the absolute quantity of alcoholic compounds such as 1-octen-3-ol and reduce the presence of esters such as methyl geranate.


Seizures and epilepsy in oncological practice: causes, course, mechanisms and treatment.
There are few data available on the causes and mechanistic basis, outcome and treatment of seizures and epilepsy in people with systemic cancer. Seizures and epilepsy in people with cancers other than primary brain tumours are reviewed here. Articles published in English, which discussed the neurological manifestations and complications of cancer and its treatment, were searched and information on the frequency, aetiology, and course of seizures and epilepsy was extracted. The frequency, aetiology and outcome of seizure disorders in patients with cancer differ from those in the general population. Intracranial metastasis, cancer drugs and metabolic disturbances are the most common causes. Infections, cerebrovascular complications of systemic cancer and paraneoplastic disorders are among the rarer causes of seizures in patients with neoplasms. Several drugs used in the treatment of cancer, or complications arising from their use, can trigger seizures through varied mechanisms. Most drug-induced seizures are provoked and do not require long-term treatment with antiepileptic drugs.


Population based cancer registry analysis of primary tracheal carcinoma.
Primary carcinomas of the trachea are rare tumors, occurring at a rate of 2.6 new cases per 1,000,000 people per year. This study investigates the large observational cohort of patients recorded in the NCI Surveillance, Epidemiology, and End Results (SEER) 1973-2004 database, and provides information regarding epidemiology, treatment, and prognosis. The SEER database was investigated, and all patients for whom primary tracheal carcinoma was the first and only cancer were investigated. Demographic information was investigated. The cohort was analyzed for variables effecting survival, including age, gender, race, histology, extent of disease, extent of surgery, use of radiation, and year of diagnosis. Between 1973 and 2004, 578 cases of primary tracheal carcinomas were reported in the SEER database. There were 322 men (55.7%) and 256 women (44.3%). Squamous cell carcinoma was the predominant histology, representing 259 tumors (44.8%). Adenoid cystic carcinoma (ACC) was the second most common tumor (16.3%). Localized, regional and distant disease was found in 140 (24.2%), 212 (36.7%), and 108 (18.7%), respectively. Twenty percent of the patients did not undergo staging. Patients with localized disease had a better prognosis than those with regional (P = 0.001) or distant disease (P = <0.001).A significant fraction of patients did not receive cancer directed local therapy; 34.3% did not undergo surgery and 29.1% did not receive any kind of radiation therapy. There was a statistically significant improved survival for patients who underwent any type of surgery in comparison with patients who did not undergo cancer directed surgery. There was no statistical benefit for patients who underwent radiation therapy.General overall 5-year survival for all patients was 27.1% (95% CI: 23.1-33.3%). Patients with localized disease had a better outcome than patients with regional or distant disease with an overall 5-year survival of 46% (95% CI: 37.3%-55.8%). Squamous cell carcinoma tumors had worse outcomes than any other histologic type, with a 5 year overall survival of 12.6% (95% CI: 8.4-17.6%). In contrast, 5-year overall survival for AACs was relatively good at 74.3% (95% CI: 63.1-82.5). For localized disease, 5-year survival was 24.7% (95% CI: 12.8-38.7%) for squamous cell carcinoma versus 90.5% (95% CI: 73.3-96.8%) for ACCs (P < 0.001). Primary tracheal tumors are very uncommon; squamous cell carcinoma is the most common histologic type, followed by ACCs. General 5-year overall survival is poor, though localized disease has better survival when compared with regional or distant disease. There is a remarkable difference in survival between squamous cell carcinoma and ACC.


Diagnosis and Treatment of Systolic Heart Failure in the Elderly.
Appropriate therapy of systolic LV dysfunction in the elderly depends on the stage of the disease process. Evidence of systolic dysfunction is best detected by clinical assessment and echocardiographic exam. While one seeks to define and treat the factors that initiated the process, one also attempts to reduce symptoms and prolong life. Therefore, with initial damage (e.g., following a large myocardial infarction), ACE inhibition or angiotensin II receptor blockade is indicated. Ã -Adrenergic receptor blockade is also indicated at this stage because of mortality reduction. As failure progresses to more symptomatic phases, Ã -blockers also appear along with ACE inhibition. Once symptoms increase and peripheral edema and central congestion occur, loop diuretics become useful to maintain dry weight. In order to prevent further myocardial cell loss, other measures, such as cessation of smoking and treatment of hypertension, are essential. Digitalis glycosides, especially in modest doses, are indicated when NYHA Class II and III symptoms occur. Surgical approaches, such as coronary revascularization, may be performed to improve LV function in ischemic disease. Therapy of heart failure seeks the reversal or attenuation of the process that initiated the syndrome, while treating the patient to relieve symptoms and prolong life. Even in very late stages of the disease, relief of symptoms can now be accomplished with modest gains in life expectancy.


Alternative mutations of a positively selected residue elicit gain or loss of functionalities in enzyme evolution.
All molecular species in an organism are connected physically and functionally to other molecules. In evolving systems, it is not obvious to what extent functional properties of a protein can change to selective advantage and leave intact favorable traits previously acquired. This uncertainty has particular significance in the evolution of novel pathways for detoxication, because an organism challenged with new xenobiotics in the environment may still require biotransformation of previously encountered toxins. Positive selection has been proposed as an evolutionary mechanism for facile adaptive responses of proteins to changing conditions. Here, we show, by saturation mutagenesis, that mutations of a hypervariable residue in human glutathione transferase M2-2 can differentially change the enzyme's substrate-activity profile with alternative substrates and, furthermore, enable or disable dissimilar chemical reactions. Crystal structures demonstrate that activity with epoxides is enabled through removal of steric hindrance from a methyl group, whereas activities with an orthoquinone and a nitroso donor are maintained in the variant enzymes. Given the diversity of cellular activities in which a single protein can be engaged, the selective transmutation of functional properties has general significance in molecular evolution.


EZH2 inhibitor DZNep blocks cell proliferation of GCB-DLBCL cells by upregulating p16.
Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Two main subgroups of DLBCL include germinal center B-cell-like (GCB) and activated B-cell-like (ABC). Molecular profiling can further classify DLBCL into four subtypes: MCD (both CD79B and MYD88 L265P), BN2 (NOTCH2 mutation or BCL6 fusion), N1 (NOTCH1 mutation), or EZB (EZH2 mutation or BCL2 fusion). EZH2 inhibitors were recommended for patients with the EZB subtype of DLBCLs; however, little is known about the therapeutic mechanisms. Our results showed that DZNep arrested G1/S phase of GCB-DLBCL cells and inhibited the cell proliferation in vitro through upregulation of p16 by demethylating its promoter. These results suggest that DZNep may have potential as a novel therapeutic agent for DFLBL therapy. This agent may serve as a novel molecular agent to be applied to GCB DLBCL.


[Tamoxifen and sex differentiation of the gonads in chick embryo].
Tamoxifen or 4-hydroxytamoxifen were injected either alone or in combination with oestradiol into 4-5 day-old chick embryos in order to study their action on the sex differentiation of the gonads. The results of the histological study of the gonads performed at the stage of 16-19 days warrant the following conclusions: None of both anti-oestrogens exerts an effect on the testes. None of both compounds modifies the sex differentiation of the female gonads. Tamoxifen exerts an antagonistic action on the feminization of the testes by oestradiol. These conclusions do not lend support to the hypothesis according to which oestrogens play a role in normal sex differentiation of the female gonads.


NLRP3 inflammasome as a sensor of micro- and nanoplastics immunotoxicity.
Micro- and nanoplastics (MNPs) are emerging pollutants with scarcely investigated effects on human innate immunity. If they follow a similar course of action as other, more thoroughly investigated particulates, MNPs may penetrate epithelial barriers, potentially triggering a cascade of signaling events leading to cell damage and inflammation. Inflammasomes are intracellular multiprotein complexes and stimulus-induced sensors critical for mounting inflammatory responses upon recognition of pathogen- or damage-associated molecular patterns. Among these, the NLRP3 inflammasome is the most studied in terms of activation via particulates. However, studies delineating the ability of MNPs to affect NLRP3 inflammasome activation are still rare. In this review, we address the issue of MNPs source and fate, highlight the main concepts of inflammasome activation via particulates, and explore recent advances in using inflammasome activation for assessment of MNP immunotoxicity. We also discuss the impact of co-exposure and MNP complex chemistry in potential inflammasome activation. Development of robust biological sensors is crucial in order to maximize global efforts to effectively address and mitigate risks that MNPs pose for human health.


Ontogeny of cardiac ornithine decarboxylase and its beta adrenergic responsiveness in the rat.
Ornithine decarboxylase (ODC) is a marker of tissue growth and development and, because sympathetic stimulation of beta adrenergic receptors acutely increases ODC in the adult rat heart, measurement of this enzyme can be used to indicate the functional intactness of the beta adrenergic receptor system in the heart. Changes in the postnatal ontogenetic pattern of this enzymatic activity may also indicate abnormal development and ODC appears to be particularly useful in evaluating the effects of prenatal insult on cardiac development. The present study examines the pattern of basal ODC activity and its developing sensitivity to beta adrenergic stimulation during the perinatal period in order to establish a data base for studies on the effect of various environmental agents on the developing cardiovascular system. ODC activity was measured in rat hearts on gestation day (GD) 20 through postnatal day (PND) 28 under saturating conditions of L-ornithine and pyridoxal 5-phosphate. Basal ODC activity fell from 3 nmol of CO2/hr/mg of protein at GD 20 to less than 0.5 nmol of CO2/hr/mg of protein at PND 18, rising again to nearly 1 nmol of CO2/hr/mg of protein at PND 22. The beta adrenergic agonist isoproterenol (10 mg/kg s.c.) resulted in peak ODC stimulation at 4 hr postinjection on PNDs 6, 14 and 21; however, no response was seen at PND 1 at this dose or at GD 20 (300 micrograms/kg s.c.). In dose-response studies, isoproterenol produced a maximal response at 10 mg/kg s.c., resulting in increases from control of 67, 230 and 1700% at PNDs 6, 14 and 21, respectively, indicating that the sensitivity of the heart to beta adrenergic stimulation increases with age, during the perinatal period.


One-pot synthesis of spring-like superstructures consisting of layered tin(IV) hydrogen phosphate nanodisks.
Spring-like superstructures consisting of layered tin(IV) hydrogen phosphate nanodisks can be obtained via a one-pot solvothermal reaction of tin tetrachloride and phosphoric acid in ethanol. These superstructures are active anode materials for the lithium-ion battery.


A group intervention to promote healthy self-concepts and guide recovery in first episode schizophrenia: A pilot study.
The stress associated with managing a first episode of schizophrenia and the secondary psychological sequelae may predispose young people to the phenomenon of illness engulfment, whereby personal identity is lost and replaced with a sense of self defined entirely by the illness. The overall objective of this pilot project was to provide an initial evaluation of the impact of a novel group intervention targeting improvement of self-concept (engulfment) and overall quality of life for young adults recovering from a first episode of schizophrenia. Fifty-two young adults diagnosed with a DSM-IV schizophrenia spectrum disorder were sequentially assigned to either a 12-week group intervention that provided members with opportunities to attain healthy self-concepts or a control group that received high quality treatment as usual. The two groups were compared on pretreatment, post-treatment, and 3-month post-treatment measures of engulfment, quality of life, and psychiatric symptoms. Allowing for dropouts, 26 subjects remained in the treatment group and 14 subjects in the control group after the 3-month follow-up. Participants in the treatment group demonstrated significant improvement in engulfment, quality of life (intrapsychic subscale) and symptoms, while the comparison group did not change. These preliminary results provide support for the benefits of a group intervention designed to enhance self-concept and to minimize the engulfing effects of illness.


Relationships between neck muscle electromyography and three-dimensional head kinematics during centrally induced torsional head perturbations.
The relationship between neck muscle electromyography (EMG) and torsional head rotation (about the nasooccipital axis) is difficult to assess during normal gaze behaviors with the head upright. Here, we induced acute head tilts similar to cervical dystonia (torticollis) in two monkeys by electrically stimulating 20 interstitial nucleus of Cajal (INC) sites or inactivating 19 INC sites by injection of muscimol. Animals engaged in a simple gaze fixation task while we recorded three-dimensional head kinematics and intramuscular EMG from six bilateral neck muscle pairs. We used a cross-validation-based stepwise regression to quantitatively examine the relationships between neck EMG and torsional head kinematics under three conditions: 1) unilateral INC stimulation (where the head rotated torsionally toward the side of stimulation); 2) corrective poststimulation movements (where the head returned toward upright); and 3) unilateral INC inactivation (where the head tilted toward the opposite side of inactivation). Our cross-validated results of corrective movements were slightly better than those obtained during unperturbed gaze movements and showed many more torsional terms, mostly related to velocity, although some orientation and acceleration terms were retained. In addition, several simplifying principles were identified. First, bilateral muscle pairs showed similar, but opposite EMG-torsional coupling terms, i.e., a change in torsional kinematics was associated with increased muscle activity on one side and decreased activity on the other side. s, whenever torsional terms were retained in a given muscle, they were independent of the inputs we tested, i.e., INC stimulation vs. corrective motion vs. INC inactivation, and left vs. right INC data. These findings suggest that, despite the complexity of the head-neck system, the brain can use a single, bilaterally coupled inverse model for torsional head control that is valid across different behaviors and movement directions. Combined with our previous data, these new data provide the terms for a more complete three-dimensional model of EMG: head rotation coupling for the muscles and gaze behaviors that we recorded.


The Opposites Attract Study of viral load, HIV treatment and HIV transmission in serodiscordant homosexual male couples: design and methods.
Studies in heterosexual HIV serodiscordant couples have provided critical evidence on the role of HIV treatments and undetectable viral load in reducing the risk of HIV transmission. There is very limited data on the risk of transmission from anal sex in homosexual male serodiscordant couples. The Opposites Attract Study is an observational prospective longitudinal cohort study of male homosexual serodiscordant partnerships running from 2012 to 2015 and conducted in clinics throughout Australia, Brazil and Thailand. Couples attend two or more clinic visits per year. The HIV-positive partner's viral load is tested and the HIV-negative partner is tested for HIV antibodies at every clinic visit. Results from any tests for sexually transmitted infections are also collected. Detailed behavioural questionnaires are completed by both partners at the time of each visit. The primary research question is whether HIV incidence is lower in those couples where the HIV-positive partner is receiving HIV treatment compared to couples where he is not receiving treatment. A voluntary semen sub-study will examine semen plasma viral load in a subsample of HIV-positive partners in Sydney, Rio de Janeiro and Bangkok. In cases of seroconversion of the initially HIV-negative partner, phylogenetic analysis will be conducted at the end of the study on virus from stored blood samples from both partners to determine if the infection came from the HIV-positive study partner. Men in new serodiscordant relationships will specifically be targeted for recruitment. This study will provide critical data on the reduction in HIV transmission risk associated with being on HIV treatment in homosexual male serodiscordant couples in different regions of the world. Data from men in new relationships will be particularly valuable given that the highest transmission risk is in the first year of serodiscordant relationships. Furthermore, the detailed behavioural and attitudinal data from the participant questionnaires will allow exploration of many contextual factors associated with HIV risk, condom use and the negotiation of sexual practice within couples.


Is nucleus-independent chemical shift scan a reliable aromaticity index for planar heteroatomic ring systems?
Density functional theoretical investigation has been performed to explore the reliability of the nucleus-independent chemical shift (NICS) scheme in assessing aromatic behavior of some planar six-membered heteroatomic systems. It has been observed that the NICS scan and the diamagnetic and paramagnetic contributions of the in-plane and out-of-plane components are quite reliable in assessing any aromatic or antiaromatic behavior in borazine. However, for boraphosphabenzene, the aromatic stabilization energy is too small to consider it as an aromatic system but the NICS scans and the homodesmotic reactions suggest an opposite trend. Interestingly, in the case of alumazene, a very shallow minimum is observed for the out-of-plane component, which suggests the presence of weak diamagnetic ring current. However, the diamagnetic and paramagnetic contribution curves to the out-of-plane component for alumazene clearly reveal a net paramagnetic contribution. Thus we may surmise that apart from the single NICS value, the NICS scan also is not a very authentic tool for the assessment of aromaticity of planar six-membered heteroatomic systems.


Vascular safe zones in hip arthroscopy.
Hip arthroscopy is an evolving surgical technique being performed in greater numbers because of advances in skill, improved technology, and increased demand. Identifying vascular safe zones using anatomic and intracapsular landmarks provides a valuable intraoperative guide to reduce the risk of damage to the femoral head blood supply during femoral neck osteoplasty and psoas tendon release. This series is presented to identify vascular safe zones for use in hip arthroscopy. Case series; Level of evidence, 4. The authors analyzed 76 consecutive contrast-enhanced magnetic resonance scans obtained from patients with diagnosed femoral acetabular impingement. High-resolution 3-dimensional images were reconstructed to visualize the vasculature. The medial femoral circumflex artery (MFCA) course was traced from the anterior thigh to the femoral head. Specific attention was paid to its proximity to the psoas tendon at the site of release and the retinacular vessel course in relation to the femoral neck using a clock-face orientation. The MFCA was found inserting on the posterior superior femoral neck from the 10:30 to 12-o'clock position on the femoral neck shaft, just posterior to the lateral synovial fold, and progressed on the femoral neck via an average of 4 retinacular vessels (range, 2-6). Ninety-seven percent of vessels were posterior to the 12-o'clock position. The MFCA passes posteriorly a mean distance of 50% ± 8% between the lesser trochanter and inferior femoral head/acetabular junction, located a mean 15 ± 0.37 mm medial to the medial cortex of the femoral neck. The MFCA was within the middle third zone in 100% of the measurements. The authors defined the following 2 safe zones: the femoral neck osteoplasty safe zone is on the anterior half of the femoral neck; the psoas tendon release safe zone is astride the middle third of the medial hip capsule (bordered by the lesser trochanter and inferior femoral head/acetabular junction).


Axonal Domain Structure as a Putative Identifier of Neuron-Specific Vulnerability to Oxidative Stress in Cultured Neurons.
Several populations of neurons are purported to degenerate in Parkinson's disease (PD). One current hypothesis suggests that vulnerable neurons in PD share common characteristics including projecting to voluminous territories and having extremely long and branched axonal domains with large numbers of neurotransmitter release sites. In this study, we used a mouse in vitro culture system to compare the axonal domain of neuronal populations suspected to be vulnerable in PD to that of neuronal populations considered at a lesser risk. In the first category, we included dopamine (DA) neurons of the substantia nigra, noradrenergic neurons of the locus coeruleus (LC), serotonin neurons of the raphe nuclei (R), and cholinergic neurons of the dorsal motor nucleus of the vagus (DMV). In the second category, we included DA neurons of the ventral tegmental area, cholinergic neurons of the hypoglossal nucleus, and cholinergic interneurons of the dorsal striatum. Validating their differential vulnerability, we find that, when compared with neurons presumed to be resilient in PD, a larger proportion of neurons presumed to be vulnerable in PD degenerate in response to cell stress induced by hydrogen peroxide. We also find that they are endowed with larger axonal domains, that are more complex, have more axonal varicosities with a higher proportion of varicosities that are positive for synaptotagmin 1 (Syt-1). Notwithstanding the obvious limitations related to the dissection of small brain nuclei and to the growth of these neurons in vitro, these findings support the hypothesis that axonal domain structure is a key characteristic of neuronal vulnerability to oxidative stress.


The renal functions following a profound hypothermia in rats.
The aftereffects of renal function were studied in rats exposed to profound hypothermia and 5 min of cardiac arrest. All experimental rats were reanimated and survived at least 1 week. It was observed that the water intake and the basal renal excretion of urine, potassium and urea were decreased 24 hr after cooling, but did return to normal within 1 week. The renal handling of a large volume of infused saline was retarded 4 hr but recovered by the end of 24 hr after hypothermia. At both 4 and 24 hr after deep cooling, clearance of inulin and p-aminohippuric acid showed there were no change in glomerular filtration rate and effective renal plasma flow. It was concluded that the renal function was altered shortly after deep cooling and 5 min of cardiac arrest, however, this alteration could be completely recovered thereafter.


Physically effective fiber: method of determination and effects on chewing, ruminal acidosis, and digestion by dairy cows.
A study was conducted to investigate the effects of physically effective neutral detergent fiber (peNDF) content of dairy cow diets containing corn silage as the sole forage on intake, chewing, ruminal pH, microbial protein synthesis, digestibility, and milk production. A second objective was to compare current methods of measuring peNDF to determine the most suitable approach for use in ration formulation. The experiment was designed as a replicated 3 x 3 Latin square using 6 lactating dairy cows with ruminal cannulas. Diets varied in peNDF content (high, medium, and low) by altering the particle length of corn silage. The physical effectiveness factors (pef) and peNDF contents of the corn silage and diets were determined based on the original (19- and 8-mm sieves) and new Penn State Particle Separator (PSPS; 19-, 8-, and 1.18-mm sieves). A dry-sieving technique that measures the proportion of particles retained on a 1.18-mm sieve was also used. The new PSPS and the 1.18-mm sieve produced similar estimates of pef and peNDF of diets but gave higher values than the original PSPS. There was a much smaller range in pef of corn silage when 3 sieves, rather than 2, were used with the PSPS (range of 0.93 to 0.96 vs. 0.41 to 0.72, respectively). Consequently, increased forage particle length in the diets increased dietary peNDF content and its intake when using the original PSPS; however, the new PSPS and the 1.18-mm sieve failed to detect changes in dietary peNDF and peNDF intake. The peNDF values estimated based on fractional NDF rather than the total NDF content were higher, but the ranking of diets was not changed. Increased intake of peNDF linearly increased digestibility of CP and tended to linearly increase digestibility of fiber in the total tract. As a result, milk yield tended to linearly increase with no effect on milk composition. Ruminal microbial protein synthesis and microbial efficiency were higher with the medium peNDF than with the high or low peNDF diets. Total chewing time and ruminating time were linearly increased with increasing dietary peNDF, whereas influence of dietary peNDF on ruminal pH and fermentation was minimal. This study showed that increasing peNDF content of diets improved fiber digestion. Of the systems used to measure peNDF, the original PSPS provided a good description of dietary particle length and its effects on chewing time and rumen pH, whereas the new PSPS provided a more consistent chewing index, the ratio of total chewing activity to peNDF, across diets varying in chop length of corn silage.


Genetic variation of antigen processing machinery components and association with cervical carcinoma.
The antigen processing machinery (APM) plays an important role in immune recognition of virally infected and transformed cells. Defective expression of several APM components is associated with progression and clinical outcome in cervical carcinoma. Genetic variation in the genes encoding APM components is known to be associated with risk of occurrence of several malignancies. However, only limited evidence exists supporting the role of single nucleotide polymorphisms (SNPs) in APM components in cervical carcinoma. We have therefore investigated the occurrence of APM component SNP genotypes and haplotypes in cervical carcinoma. Thirteen coding SNPs in the LMP2, LMP7, TAP1, TAP2, and ERAP1 genes were genotyped in 127 cervical carcinoma patients and 124 controls. Individual genotype and allele distributions were assessed by single-marker analysis. Effects of various SNP combinations were estimated by haplotype construction and subsequent haplotype interaction analysis. Significant haplotypes were modeled on disease risk. Allele distributions at the LMP7-145, TAP2-651, ERAP1-127, and ERAP1-730 loci differed significantly between cases and controls with the major allele at the LMP7 and TAP2 loci and the minor allele at both ERAP1 loci associated with increased cervical carcinoma risk. A combination of the two haplotypes spanning these loci was associated with a three-fold increased risk (OR = 3.024; P << 0.001); approximately 12% of all cervical carcinoma occurrences were attributable to this combination. Our data indicate that combined genetic variation in the TAP2, LMP7, and ERAP1 genes is associated with increased cervical carcinoma risk.


[The research project: financing and management].
Basic and clinical research is accomplished by projects. The design of a project is not only based on the scientific content but also on its financing and management. This article wants to illustrate the correct modalities for project financing and project management in a scientific project.


Parturition itself is the basis for fetal adrenal involution.
Newborn infants show a postnatal decline in androgen levels as the fetal adrenal glands involute. Placental factors up-regulate dehydroepiandrosterone sulfate (DHEA-S) generation. Hence, regardless of age, parturition will result in fetal adrenal involution and decline in DHEA-S levels. Premature neonates (n = 30) with gestational age 26-35 wk were studied. Adrenal volume by ultrasonography and serum DHEA-S, cortisol, and androstendione levels were followed weekly between d 1 and 28 of life. Serum DHEA-S was high on d 1 of life, declining rapidly regardless of gestational age during the first week of life (P < 0.001), and serum androstenedione and cortisol levels followed a similar pattern. Androstenedione levels showed a rise as of d 21 of life in boys but not in girls. The adrenals decreased in ultrasonographic volume from d 1 to 14 of life (P < 0.001), regardless of gestational age. Involution of the adrenal is faster than previously reported and, regardless of gestational age, occurs within the first week of life in terms of hormone secretion and within 2 wk in adrenal size. Involution involves a decline in DHEA-S but also in androstenedione and cortisol secretion, with a change in enzymatic activity. Males and females differ in their androstenedione levels and enzymatic activity. Parturition itself is the basis for fetal adrenal involution, supporting a key role for placental factors in maintaining the fetal adrenal and generating adrenal androgens.


Interdependency of selected metabolic variables in an animal model of metabolic syndrome.
In the present study, the correlation between the percentage of glycated hemoglobin, taken as representative of changes in glucose homeostasis, and selected variables was investigated. Rats were treated for 8 weeks with diets containing 64% starch and 5% sunflower oil or containing 64% D-fructose mixed with: 5% sunflower oil; 3.4% sunflower oil and 1.6% salmon oil; or 3.4% sunflower oil and 1.6% safflower oil. Positive correlations were found between glycated hemoglobin and plasma albumin, urea, creatinine, phospholipids, triglycerides and total cholesterol, liver cholesterol, triglyceride and phospholipid content, and the plasma, liver, heart, kidney, soleus muscle and visceral adipose tissue content of thiobarbituric acid reactive substances, carbonyl derivatives and hydroperoxides. Inversely, negative correlations were observed between glycated hemoglobin and plasma calcium, iron and HDL-cholesterol concentrations, liver, heart, kidney, soleus muscle and visceral adipose tissue superoxide dismutase and catalase activity; as well as plasma, liver, heart, kidney, soleus muscle and visceral adipose tissue nitric oxide content. Only the liver glucokinase activity and liver, heart, kidney, soleus muscle and visceral adipose tissue glutathione reductase activity failed to display a significant correlation with glycated hemoglobin. These findings confirm the hypothesis that there is a close association between glucose homeostasis and other variables when considering the effects of long-chain polyunsaturated ω3 and ω6 fatty acids in rats with fructose-induced metabolic syndrome.


Evaluation of the Psychometric Properties of the Health Assessment Questionnaire (HAQ) in a Population of Individuals With Multiple Sclerosis.
The Health Assessment Questionnaire (HAQ) has been translated into many languages and it has been classified as the predictor of disability and medical costs, however, the psychometric properties of the HAQ have never been studied in a population with neurological disease. The purpose of this study was the evaluation of the psychometric properties of HAQ in a population of individuals with multiple sclerosis (MS). This cross-sectional study was conducted with patients diagnosed with MS. The evaluation tools administered were the 36-item short form health survey (SF-36) to evaluate the health state of the patients and HAQ and to evaluate the limitations of the activities of daily living (ADL). A total of 34 patients were included in this study. Cronbach's alpha assessed the internal consistency of the HAQ, and it is equal to 0.94. The study revealed some significant correlations between the dimensions of the SF-36 and the sub-categories of the HAQ using Pearson's Correlation Coefficient. Significant correlations emerged between the demographic and clinical characteristics of patients and the subcategories of HAQ. The HAQ is a valid and reliable tool to assess the limitations of the activities of daily living, and it could provide for the healthcare and rehabilitation sector with an additional evaluation tool.


Recurrence of IgG4-related disease following treatment with rituximab.
A 54-year-old woman with suspected low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type of the eyelids underwent rituximab-containing chemotherapy. She initially responded to the rituximab therapy, but later experienced two recurrences over a 3-year period. Biopsy specimens and a review of her previous histology revealed that she had had immunoglobulin G4-related disease at the initial presentation. Although IgG4-related disease seems to respond well to rituximab therapy, long-term follow up, including disease monitoring, is needed to evaluate disease remission.


The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules.
The receptor protein tyrosine phosphatases gamma (PTPRG) and zeta (PTPRZ) are expressed primarily in the nervous system and mediate cell adhesion and signaling events during development. We report here the crystal structures of the carbonic anhydrase-like domains of PTPRZ and PTPRG and show that these domains interact directly with the second and third immunoglobulin repeats of the members of the contactin (CNTN) family of neural recognition molecules. Interestingly, these receptors exhibit distinct specificities: PTPRZ binds only to CNTN1, whereas PTPRG interacts with CNTN3, 4, 5, and 6. Furthermore, we present crystal structures of the four N-terminal immunoglobulin repeats of mouse CNTN4 both alone and in complex with the carbonic anhydrase-like domain of mouse PTPRG. In these structures, the N-terminal region of CNTN4 adopts a horseshoe-like conformation found also in CNTN2 and most likely in all CNTNs. This restrained conformation of the second and third immunoglobulin domains creates a binding site that is conserved among CNTN3, 4, 5, and 6. This site contacts a discrete region of PTPRG composed primarily of an extended beta-hairpin loop found in both PTPRG and PTPRZ. Overall, these findings implicate PTPRG, PTPRZ and CNTNs as a group of receptors and ligands involved in the manifold recognition events that underlie the construction of neural networks.


Nosema apis and Nosema ceranae Tissue Tropism in Worker Honey Bees (Apis mellifera).
The microsporidia Nosema apis and Nosema ceranae are major honey bee pathogens that possess different characteristics in terms of the signs they produce, as well as disease development and transmission. Although the ventricular epithelium is generally considered the target tissue, indirect observations led to speculation that N. ceranae may also target other structures, possibly explaining at least some of the differences between these 2 species. To investigate the tropism of Nosema for honey bee tissues, we performed controlled laboratory infections by orally administering doses of 50 000 or 100 000 fresh mature spores of either species. The fat body was isolated from the infected bees, as well as organs from the digestive (esophagus, ventriculus, ileum, rectum), excretory (Malpighian tubules), circulatory (aorta, heart), respiratory (thoracic tracheas), exocrine (hypopharyngeal, mandibular and labial, cephalic, thoracic salivary glands), and sensory/nervous (brain, eyes and associated nerve structures, thoracic nerve ganglia) systems. Tissues were examined by light and electron microscopy at 7, 10, and 15 days postinfection. Both Nosema species were found to infect epithelial cells and clusters of regenerative cells in the ventriculus, and while the ileum and rectum contained spores of the microsporidia in the lumen, these structures did not show overt lesions. No stages of the parasites or cellular lesions were detected in the other organs tested, confirming the high tropism of both species for the ventricular epithelium cells. Thus, these direct histopathological observations indicate that neither of these 2 Nosema species exhibit tropism for honey bee organs other than the ventriculus.


Highly valued despite burdens: Qualitative implementation research on rapid tests for hospital-based SARS-CoV-2 screening.
Antigen-based rapid diagnostic tests (RDTs) for SARS-CoV-2 have good reliability and have been repeatedly implemented as part of pandemic response policies, especially for screening in high-risk settings (e.g., hospitals and care homes) where fast recognition of an infection is essential. However, evidence from actual implementation efforts and associated experiences is lacking. We conducted a qualitative study at a large tertiary care hospital in Germany to identify step-by-step processes when implementing RDTs for the screening of incoming patients, as well as stakeholders' implementation experiences. We relied on 30 in-depth interviews with hospital staff (members of the regulatory body, department heads, staff working on the wards, staff training providers on how to perform RDTs, and providers performing RDTs as part of the screening) and patients being screened with RDTs. Despite some initial reservations, RDTs were rapidly accepted and adopted as the best available tool for accessible and reliable screening. Decentralized implementation efforts resulted in different procedures being operationalized across departments. Procedures were continuously refined based on initial experiences (e.g., infrastructural or scheduling constraints), pandemic dynamics (growing infection rates), and changing regulations (e.g., screening of all external personnel). To reduce interdepartmental tension, stakeholders recommended high-level, consistently communicated and enforced regulations. Despite challenges, RDT-based screening for all incoming patients was observed to be feasible and acceptable among implementers and patients, and merits continued consideration in the context of high infection and stagnating vaccination rates.


Audit of a network of sexually transmitted infections centred in South Wales.
The aim of this article is to audit the distribution and frequency of sexually transmitted infections (STIs) within a sexual network centred in South Wales. After diagnosis of a new case of HIV in February 2007, partner notification, HIV and STI testing were undertaken. Those traced were given information regarding safe sex practices and informed they had been in contact with HIV. Genitourinary (GU) medicine case-notes of contacts identified in the network were reviewed from February 2007 to 1 July 2008. Frequency and distribution of new diagnoses of STIs made on original identification in the network in 2007 were compared with subsequent new diagnoses within the network. One hundred and eighteen men who have sex with men (MSMs) and five women were identified in the original network in 2007. By 1 July 2008, 65 new sexual contacts (all MSMs) were added to the network and there were 25 new STI diagnoses in 13 contacts. Seven contacts originally identified in the cluster in 2007 were diagnosed with 16 of the new STIs. In conclusion, the sexual network has evolved by increasing in size with multiple new STIs diagnosed. The highest risk of STIs occurred in relatively few individuals. Standard interventions in health promotion in the GU medicine setting were not universally successful in preventing high-risk behaviour.


[Current status and future prospect of enzyme replacement therapy for Fabry disease].
Fabry disease is characterized by deficient activity of α-galactosidase A, which results in accumulation of glycolipids, such as globotriaosylceremide, in various tissue. Clinical symptoms are varied. In childhood, pain in extremities, hypohidrosis, and angiokeratoma are main symptoms, In adulthood, renal, cardiac and cerebrovascular symptoms are occurred In past, only symptomatic treatments were available. In early 2000th, enzyme replacement therapy was developed after positive results of clinical trials. Ten years after approval, the data of long term safety and efficacy of enzyme replacement.


Promotion of Parenting and Mental Health Needs among Chinese Women Living in Japan: A Qualitative Study.
Chinese women raising children in Japan tend to experience high parenting stress and poor mental well-being. However, their specific parenting and mental health promotion needs remain unknown. This study aimed to explore the parenting and mental health promotion needs of Chinese women living in Japan and provide recommendations to guide interventions. Semi-structured in-depth interviews were conducted. Participants included 15 women aged 28-39 years who were pregnant or rearing a child younger than six years old. Thematic analysis was performed for data analysis. More than half of the participants experienced mental health problems, such as depressive symptoms and child-rearing stress. Four themes relating to their needs were identified: concrete support, information provision, caring and understanding, and social network building. Information provision and social network building should be emphasized as practical social support mechanisms to improve these women's mental health. Furthermore, a mental health promotion intervention should be developed to address this vulnerable population's needs. Healthcare providers and public health workers should help improve the social support systems of Chinese women in Japan to prevent mental health problems. Potential transcultural education can, arguably, help healthcare providers better understand transcultural care.