Narrative health research: exploring big and small stories as analytical tools.
In qualitative health research many researchers use a narrative approach to study lay health concepts and experiences. In this article, I explore the theoretical linkages between the concepts narrative and health, which are used in a variety of ways. The article builds on previous work that conceptualizes health as a multidimensional, positive, dynamic and morally dilemmatic yet meaningful practice. I compare big and small stories as analytical tools to explore what narrative has to offer to address, nuance and complicate five challenges in narrative health research: (1) the interplay between health and other life issues; (2) the taken-for-granted yet rare character of the experience of good health; (3) coherence or incoherence as norms for good health; (4) temporal issues; (5) health as moral practice. In this article, I do not present research findings per se; rather, I use two interview excerpts for methodological and theoretical reflections. These interview excerpts are derived from a health promotion study in the Netherlands, which was partly based on peer-to-peer interviews. I conclude with a proposal to advance narrative health research by sensitizing researchers to different usages of both narrative and health, and the interrelationship(s) between the two.


Pharmaceutical and Endocrine Disruptor Compounds in Surface and Wastewater in San Marcos, Texas.
Water resource recovery facilities (WRRFs) and hospitals are major point sources of pharmaceuticals and endocrine disrupting compounds (EDCs) in aquatic environments. This study investigated the removal efficiencies of 23 known or suspected EDCs through the San Marcos WRRF to determine which treatment process was the most effective at removal. Results from samples collected at the hospital indicate that the hospital discharge is contributing to the concentration of these compounds in the San Marcos wastewater collection system (0.05-140 μg/L concentrations). The most frequently detected compounds in the WRRF influent included acetaminophen, nonylphenol, caffeine, benzophenone, N,N-diethyl-m-toluamide (DEET), bisphenol A (BPA), and triclosan. Comparison of influent and effluent concentrations showed that the San Marcos WRRF is effectively removing (>92%) of these compounds, with the exception of carbamazepine and tris(2-chloroethyl) phosphate (TCEP). These preliminary results will be used to guide future improvements within the WRRF.


Overexpression of p53 but not Rb in the cytoplasm of neurons and small vessels in an autopsy of a patient with Cockayne syndrome.
Cockayne syndrome presents senescence-like changes starting in early infancy; however, the mechanism of premature aging remains unclear. In an autopsy of a 23-year-old woman with Cockayne syndrome, we evaluated the correlation between Cockayne pathology and the expression patterns of the senescence-associated proteins p53 and Rb. Neuropathological findings in this case revealed basal ganglia calcification, tigroid leukodystrophy, bizarre reactive astrocytes, severe cerebellar atrophy with loss of Purkinje cells, and arteriolar/neuronal calcifications in the hypothalamus. Multiple arteriolar calcifications and sclerotic changes were seen in the central nervous system and kidney, but the endothelium of the aorta and coronary arteries remained intact appropriately for the individual's age without any finding of arteriosclerosis. Overexpression of p53 protein was confirmed in the cytoplasm of neurons in the basal ganglia, thalamus, hypothalamus, hippocampus and cerebellum, of arteriolar endothelial cells of the cerebrum and renal glomerular capillaries, and of cutaneous epithelial cells. The distribution of p53 overexpression was coincident with that of pathological alteration, such as neuronal loss, calcification and atrophy. High expression of p53 was localized in the cytoplasm, not in the nucleus. In contrast to p53, Rb was not expressed in any senescence lesion. In terms of senescence, distinct differences are found among organs in a patient with Cockayne syndrome. This segmental progeria differs from natural aging, and implicates p53 overexpression in the etiology of CS.


Socio-economic effect on caries. Incidence data among Swedish 12-14-year-olds.
To assess whether socioeconomic factors are associated with the progression of caries, independently of a previous history of caries. In 1995, as part of a longitudinal study of preventive measures, 3373 Swedish 12-year-olds were examined for caries and answered a questionnaire regarding socioeconomic level (SEL), ethnicity and residential area. The examination was repeated in 1997 when 3109 of the teenagers participated. Baseline caries and increments in the incidence of caries were computed. The influence of structural variables on baseline caries as well as a 2-year increment were analysed by means of Poisson regression. The risk of having caries as 12-year-olds was greater in workers' and immigrants' children, as well as in urban teenagers. The risk of developing new caries was most influenced by an earlier experience of caries. The social gradient was, however, still visible when a previous experience of caries was accounted for. The pattern found in the cross-sectional data from 1995, with more caries in children from workers' families, therefore prevailed in the increment data. Irrespective of earlier caries status there is a social gradient in caries progression. It therefore seems that the preventive methods do not function to the equal benefit of all children.


Blood-Brain Barrier Disruption and Perivascular Spaces in Small Vessel Disease and Neurodegenerative Diseases: A Review on MRI Methods and Insights.
Perivascular spaces (PVS) and blood-brain barrier (BBB) disruption are two key features of cerebral small vessel disease (cSVD) and neurodegenerative diseases that have been linked to cognitive impairment and are involved in the cerebral waste clearance system. Magnetic resonance imaging (MRI) offers the possibility to study these pathophysiological processes noninvasively in vivo. This educational review provides an overview of the MRI techniques used to assess PVS functionality and BBB disruption. MRI-visible PVS can be scored on structural images by either (subjectively) counting or (automatically) delineating the PVS. We highlight emerging (diffusion) techniques to measure proxies of perivascular fluid and its movement, which may provide a more comprehensive understanding of the role of PVS in diseases. For the measurement of BBB disruption, we explain the most commonly used MRI technique, dynamic contrast-enhanced (DCE) MRI, as well as a more recently developed technique based on arterial spin labeling (ASL). DCE MRI and ASL are thought to measure complementary characteristics of the BBB. Furthermore, we describe clinical studies that have utilized these MRI techniques in cSVD and neurodegenerative diseases, particularly Alzheimer's disease (AD). These studies demonstrate the role of PVS and BBB dysfunction in these diseases and provide insight into the large overlap, but also into the differences between cSVD and AD. Overall, MRI techniques may provide valuable insights into the pathophysiological mechanisms underlying these diseases and have the potential to be used as markers for disease progression and treatment response. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.


A Compact Broadband Common-Mode Suppression Filter That Integrates Series-Mushroom into Defected Corrugated Reference Plane Structures.
This paper proposes a common-mode noise suppression filter scheme for use in the servers and computer systems of high-speed buses such as SATA Express, HDMI 2.0, USB 3.2, and PCI Express 5.0. The filter uses a novel series-mushroom-defected corrugated reference plane (SMDCRP) structure. The measured results are similar to the full-wave simulation results. In the frequency domain, the measured insertion loss of the SMDCRP structure filter in differential mode (DM) can be kept below -4.838 dB from DC to 32 GHz and can maintain signal integrity characteristics. The common-mode (CM) suppression performance can suppress more than -10 dB from 8.81 GHz to 32.65 GHz. Fractional bandwidth can be increased to 115%, and CM noise can be ameliorated by 55.2%. In the time domain, using eye diagram verification, the filter shows complete differential signal transmission capability and supports a transmission rate of 32 Gb/s for high-speed buses. The SMDCRP structure filter reduces the electromagnetic interference (EMI) problem and meets the quality requirements for the controllers and sensors used in the server and computer systems of high-speed buses.


Pulmonary vein pseudoaneurysm secondary to oesophageal stent displacement.
Oesophageal stents allow endoscopic treatment of several oesophageal disorders. Although oesophageal stents are generally safe, early and late adverse events may occur. We present a previously unpublished complication consisting of a pulmonary vein pseudoaneurysm secondary to an oesophageal stent displacement.


Peptide-functionalized graphene oxide quantum dots as colorectal cancer theranostics.
Colorectal cancer (CRC) accounts for approximately 10% of all new cancer cases worldwide with significant morbidity and mortality. The current imaging techniques are lacking diagnostic precision while traditional chemotherapeutic strategies are limited by their adverse side effects and poor response in advanced stages. Targeted nanoparticles (NPs) can specifically bind to surface antigens on cancer cells and provide effective delivery of diagnostic and chemotherapeutic agent. Placenta-specific protein 1 (PLAC-1) is overexpressed in CRC and can be used as a target for detection and treatment of the disease. The aim of this work was to develop a targeted nanotheranostic agent for early diagnosis and inhibition of the malignant progression and metastasis of CRC. Graphene oxide quantum dots (QD) were covalently labeled with a peptide (GILGFVFTL) having high affinity to PLAC-1. The covalent coupling between the QD and the peptide was confirmed using a series of physicochemical and morphological characterization techniques. Confocal microscopy was used to evaluate the uptake of QD and QD-P in HCT-29, HT-116 and LS-180 CRC cell lines. Selective targeting of antigen PLAC-1 overexpressed on HT-29 and HCT-116 cells was measured by immunofluorescence. Cell proliferation, cell invasion and extent of PLAC-1 expression in CRC cells after treatment with QD and QD-P were determined. The prepared QD-P showed a significant increase in targeting and specific uptake in cells expressing the antigen PLAC-1 compared to non-functionalized QD. Treatment with QD-P also increased the cell cytotoxicity, reduced the invasiveness of HT-29 and HCT-116 cells by 38% and 62%, respectively, and downregulated the expression of PLAC-1 by 53% and 33%, respectively. These results highlight the potential use of QD-P as a theranostic agent for the detection and treatment of CRC cells expressing the antigen PLAC-1.


Bilinear Model for the Size-Dependency of the CYP3A4 Inhibitory Activity of Structurally Diverse Compounds.
A quantitative structure-activity relationship analysis of the inhibitory activity of structurally diverse compounds on recombinant human CYP3A4 is presented using a bilinear approach based on our previously developed LinBiExp model. Using only two main descriptors, molecular size and an indicator variable for the presence of triazole/imidazole moieties, this approach can account for close to 65 % of the variability in the inhibitory activity of more than 70 compounds and provides clear evidence that molecular size plays an important, but nonlinear role. Strongest inhibitory activity is likely to occur for compounds close to an optimal size, which is roughly that of the well-know CYP3A4-inhibitor ketoconazole. The activity-limiting role of size was also confirmed on a large dataset of 3438 compounds (PubChem Bioassay AID 884). This model provides a simple, intuitive interpretation and can serve as the starting point for more complex descriptions of the CYP3A4 inhibitory activity.


Driving current through single organic molecules.
We investigate electronic transport through two types of conjugated molecules. Mechanically controlled break junctions are used to couple thiol end groups of single molecules to two gold electrodes. Current-voltage characteristics ( IVs) of the metal-molecule-metal system are observed. These IVs reproduce the spatial symmetry of the molecules with respect to the direction of current flow. We hereby unambiguously detect an intrinsic property of the molecule and are able to distinguish the influence of both the molecule and the contact to the metal electrodes on the transport properties of the compound system.


Psychological and emotional development, intellectual capabilities, and body image in short normal children.
It is well established that children with short stature frequently have problems in cognitive development, personality, self-esteem and social relations. This is partly due to the fact that many parents view them as more vulnerable than other children of normal stature and do not allow them to face the normal experiences that correspond to their actual age. The aim of the present study was to assess, through the administration of appropriate psychological tools, a series of psychological and cognitive characteristics [i.e. anxiety, depression, good adjustment, social functioning, feeling of guilt, interpersonal relationship, intelligence quotient (IQ)], as well as variables linked to development of body image, in a group of children suffering from normal growth variants [familial short stature (FSS), no. 10, 4 males/6 females; with constitutional growth delay (CGD), no. 4,4 males; height standard deviation score (HSDS) ranging between -2.4 and -1.9] and in a control group children of normal stature (HSDS between -0.1 and +0.1). Children with short stature significantly differed from normal statured controls as far as Colored Progressive Matrices (CPMs, centiles), IQ (IQ, obtained using the Goodenough test), "Good Adjustment" (Draw-a-Person index, DAP), "Feelings of Guilt" (DAP index), "Height" (as emerges from drawings of the body) are concerned. Significant relationships were found between the height of the subjects (in centiles) and cognitive skills, measured both using CPMs (r=0.408; p=0.017) and Draw-a-Man (DAM) (r=0.359; p=0.037) and between height and feelings of guilt (r=0.325; p=0.027), measured using DAP. CPM scores correlated positively with the "Good Adjustment" index of DAP (r=0.354; p=0.05) and negatively with Children's Depression Inventory (CDI) (r=-0.609; p=0.01), "School Anxiety" index (r=-0.427; p=0.05) and "Total Anxiety" index (r=-0.436; p=0.05) of the Anxiety Scale Questionnaire for the Age of Development, and with 2 indices of DAP, namely, "Feelings of Guilt" (r=-0.461; p=0.01) and "Interpersonal Relationships (Difficulty in Establishing)" (r=-0.455; p=0.01). A significant positive correlation was found between the height of the subject and both the measurement of the "Body of Drawing 3" (r=0.450, p=0.01) and the measurement of the "Body of Drawing 4" (r=0.461, p=0.01), as well as the with the "Total Height of Drawing 4" (r=0.464, p=0.01). Higher indices for anxiety, depression, feelings of guilt and difficulty in establishing interpersonal relationships and lower indices for good adjustment were found in children with CGD as compared to subjects with FSS or normal statured children. Although further additional studies on larger samples are needed to confirm these preliminary observations, the present study underlines the importance of psychological support also during the growth and development in short normal children.


Microfluidic Encapsulation of Prickly Zinc-Doped Copper Oxide Nanoparticles with VD1142 Modified Spermine Acetalated Dextran for Efficient Cancer Therapy.
Structural features of nanoparticles have recently been explored for different types of applications. To explore specific particles as nanomedicine and physically destroy cancer is interesting, which might avoid many obstacles in cancer treatment, for example, drug resistance. However, one key element and technical challenge of those systems is to selectively target them to cancer cells. As a proof-of-concept, Prickly zinc-doped copper oxide (Zn-CuO) nanoparticles (Prickly NPs) have been synthesized, and subsequently encapsulated in a pH-responsive polymer; and the surface has been modified with a novel synthesized ligand, 3-(cyclooctylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl] benzenesulfonamide (VD1142). The Prickly NPs exhibit very effective cancer cell antiproliferative capability. Moreover, the polymer encapsulation shields the Prickly NPs from unspecific nanopiercing and, most importantly, VD1142 endows the engineered NPs to specifically target to the carbonic anhydrase IX, a transmembrane protein overexpressed in a wide variety of cancer tumors. Intracellularly, the Prickly NPs disintegrate into small pieces that upon endosomal escape cause severe damage to the endoplasmic reticulum and mitochondria of the cells. The engineered Prickly NP is promising in efficient and targeted cancer treatment and it opens new avenue in nanomedication.


The results of aggressive regional operation in the treatment of cancer of the floor of the mouth.
We reviewed the records of 94 patients with cancer of the floor of the mouth who were treated during a 15-year period to assess the results of an aggressive regional surgical approach. The primary tumor was excised with a 2 cm margin of normal tissue. A marginal or segmental mandibulectomy was performed in 84 of 94 patients. An ipsilateral radical neck dissection was performed in 86 of 94 patients. Contralateral suprahyoid dissection was combined with ipsilateral radical neck dissection in 52 patients. Bilateral radical neck dissection was performed in 10 patients. In the 1 to 16-year follow-up period, local/regional control was achieved in 91% of stage I patients, 83% of stage II patients, 68% of stage III patients, and 48% of stage IV patients. Determinant 5-year survival rates were T1--72%, T2--47%, T3--25%, and T4--28%.


Isolation Systems and its Effectiveness in Oral and Maxillofacial Surgery: A Systematic Review.
The success of restoration processes depends on the efficient control of moisture and microorganisms. Dental restorative procedures frequently use rubber dams as an isolation technique. There is still room for evidence-based discussion over how rubber dam use affects the durability and caliber of dental restorations. In this review, the effects of rubber dam isolation vs alternative isolation techniques for dental restorative procedures are compared. An extensive online search in the various databanks of the EMBASE, Medline, Pubmed, and Scopus was conducted. The keywords searched were "isolation, oral surgery, dental surgery, retractors, rubber dam, and methods of isolation." The studies selected were longitudinal research design and randomized trials. To ascertain the risk of bias, meta-analysis was carried out. The outcome was measured as the successful restoration at the end of follow-up period representing the thorough isolation. A total of 1342 people were involved in six studies from across the world that were carried out between 2010 and 2015. High bias risk existed in all the studies. Five investigations compared the rubber dam vs cotton rolls. Due to discrepancies in the data supplied, one study was omitted from the analysis. Three of the four trials that were still running showed restored survival rates with all having a follow-up of at least six months. The survival of the restored composite teeth for six months in rubber dam isolation with odds ratio of 2.29, 1.38, and 1.00 at the end of six months, one year and one and half year respectively. However, the evidence was very low and speculative. The isolation was seen effective in the primary teeth specifically for the proximal lesions. None of the included studies discussed side effects or provided information on the treatment's upfront costs. The application of rubber dams in dental techniques may result in successful outcome compared to cotton rolls, according to some low-certainty evidence revealed in this research. Other times, the evidence is really ambiguous. It is necessary to conduct additional, high-quality studies investigating how rubber dam use affects various restorative procedures.


Economic evaluations of trastuzumab in HER2-positive metastatic breast cancer: a systematic review and critique.
Published economic evaluations of trastuzumab for the treatment of HER2-positive metastatic breast cancer have arrived at different conclusions regarding the cost-effectiveness of trastuzumab, despite comparative efficacy being demonstrated by a small set of randomised controlled trials (RCTs). This article aims to provide insight into the quality of the evaluations and explore the possible drivers of the conflicting conclusions. A systematic literature review was conducted to identify all published economic evaluations that compared the incremental costs and outcomes of trastuzumab versus a comparator. Fifteen economic evaluations were identified. In the evaluations that estimated efficacy using an RCT, the key drivers of the conclusions regarding cost-effectiveness were: the approach used to estimate overall survival in the control group given crossover to trastuzumab following progression in the trials; the inclusion of treatment beyond progression; inclusion of wastage due to unused vial portions, adverse events, and the cost of HER2 testing. Four evaluations used non-randomised approaches to estimate efficacy, thus introducing the potential for confounding. As a result these evaluations reported relatively optimistic estimates of comparative effectiveness. Finally the evaluations used different thresholds to determine whether treatment with trastuzumab was cost-effective. There were numerous drivers of the different conclusions regarding the cost-effectiveness of trastuzumab, many of which are due to judgements made by the authors when translating data from RCTs. Many of the potential drivers were not identified by the published systematic reviews of economic evaluations and perhaps more remain unidentified because of inconsistent and limited reporting.


Changes of periodontal parameters following apical surgery: a prospective clinical study of three incision techniques.
To evaluate periodontal changes following apical surgery, and to relate changes to the type of incision and to the type of restoration present at the gingival margin (GM). Periodontal parameters [probing depth (PD), level of GM and clinical attachment, plaque and bleeding indices] were recorded at baseline and 1 year following apical surgery. The periodontal changes were calculated and assessed with respect to the incision technique (intrasulcular incision, papilla base incision and submarginal incision), as well as to the presence and type of a restoration margin in contact with the gingiva. One hundred and eighty-four teeth could be evaluated. No significant differences between the three incision techniques were found regarding changes in PDs and plaque index over time. However, significant differences between the intrasulcular and submarginal incisions were found for changes in levels of GM and clinical attachment. For example, with the intrasulcular incision, there was a mean recession of 0.42 mm at buccal sites, whereas using the submarginal incision there was a gain of 0.05 mm. No statistically significant influence could be demonstrated for the presence and type of restoration margins, or the smoking habit of the patient. The type of incision was found to affect changes significantly in periodontal parameters within an observation period of 1 year following apical surgery, whereas the restoration margin and smoking habit did not prove to have any significant effect.


THIP, a hypnotic and antinociceptive drug, enhances an extrasynaptic GABAA receptor-mediated conductance in mouse neocortex.
THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is a selective GABA(A) receptor agonist with a preference for delta-subunit containing GABA(A) receptors. THIP is currently being tested in human trials for its hypnotic effects, displaying advantageous tolerance and addiction properties. Since its cellular actions in the neocortex are uncertain, we studied the effects of THIP on neurons in slices of frontoparietal neocortex of 13- to 19-day-old (P13-19) mice. Using whole-cell patch-clamp recordings, we found that the clinically relevant THIP concentration of 1 muM induced a robust tonic GABA(A)-mediated current in layer 2/3 neurons. In comparison, only a minute tonic current was induced by mimicking in vivo endogenous GABA levels. Miniature IPSCs were not affected by 1 muM THIP suggesting an extrasynaptic site of action. The EC(50) for THIP was 44 muM. In accordance with the stronger expression of delta-containing receptors in superficial neocortical layers, THIP induced a 44% larger tonic current in layer 2/3 than in layer 5 neurons. Finally, monitoring spontaneously active neocortical neurons, THIP caused an overall depression of inhibitory activity, while enhancing excitatory activity prominently. Our studies suggest that THIP activates an extrasynaptic GABA(A) receptor-mediated conductance in the neocortex, which may alter the cortical network activity.


First clinical inflammatory demyelinating events of the central nervous system in a population aged over 70 years: A multicentre study.
Few data are available regarding patients with very late-onset inflammatory demyelinating events. (VLO-IDE). The aim of this study was to describe the clinical, biological, and radiological characteristics and aetiological diagnosis of very late first inflammatory demyelinating events of the central nervous system. We conducted a national descriptive retrospective multicentre study on a case series of patients aged >70 years at the time of VLO-IDE. Patients were recruited from a national call on behalf of the 'Société Francophone de la Sclérose en Plaques' (French Multiple Sclerosis Society). Twenty-five patients were referred (F:M sex ratio 2.1:1). The most frequent clinical impairment was a spinal cord deficit (23/25), usually severe (disability score, median EDSS 4.5 [2-9.5]). Spinal cord lesions were usually extensive, spanning at least three segments (11/25), and large brain lesions were also observed (lesions >20 mm in 6/25). The final aetiological diagnoses comprised multiple sclerosis (9/25), neuromyelitis optica spectrum disorders (7/25), neurosystemic lupus erythematosus (2/25), transverse myelitis without aetiological diagnosis (6/25) and optic neuritis (1/25). This study highlights a particular phenotype of first clinical inflammatory demyelinating events in predominantly female patients aged >70 years who have severe motor impairment with common longitudinal extensive myelitis and large and common very active radiological inflammatory lesions. Neuromyelitis optica spectrum disorders seem overrepresented.


Factors which abolish hypoglycemic seizures do not increase cerebral glycogen content in vitro.
The brain is heavily dependant on glucose for its function and survival. Hypoglycemia can have severe, irreversible consequences, including seizures, coma and death. However, the in vivo content of brain glycogen, the storage form of glucose, is meager and is a function of both neuronal activity and glucose concentration. In the intact in vitro hippocampus isolated from mice aged postnatal days 8-13, we have recently characterized a novel model of hypoglycemic seizures, wherein seizures were abolished by various neuroprotective strategies. We had hypothesized that these strategies might act, in part, by increasing cerebral glycogen content. In the present experiments, it was found that neither decreasing temperature nor increasing glucose concentrations (above 2 mM) significantly increased hippocampal glycogen content. Preparations of isolated frontal neocortex in vitro do not produce hypoglycemic seizures yet it was found they contained significantly lower glycogen content as compared to the isolated intact hippocampus. Further, the application of either TTX, or a cocktail containing APV, CNQX and gabazine, to block synaptic activity, did not increase, but paradoxically decreased, hippocampal glycogen content in the isolated intact hippocampus. Significant decreases in glycogen were noted when neuronal activity was increased via incubation with l-aspartate (500 muM) or low Mg(2+). Lastly, we examined the incidence of hypoglycemic seizures in hippocampi isolated from mice aged 15-19 and 22-24 days, and compared it to the incidence of hypoglycemic seizures of hippocampi isolated from mice aged 8-13 days described previously (Abdelmalik et al., 2007 Neurobiol Dis 26(3):646-660). It was noted that hypoglycemic seizures were generated less frequently, and had less impact on synaptic transmission in hippocmpi from PD 22-24 as compared to hippocampi from mice PD 15-19 or PD 8-13. However, hippocampi from 8- to 13-day-old mice had significantly more glycogen than the other two age groups. The present data suggest that none of the interventions which abolish hypoglycemic seizures increases glycogen content, and that low glycogen content, per se, may not predispose to the generation of hypoglycemic seizures.


[A Case of Retroperitoneal Liposarcoma Resected 6 Times in 24 Years].
We report a long-surviving case of retroperitoneal liposarcoma requiring 6 operations in 24 years. A 56-year-old female was diagnosed with liposarcoma and it was resected for the first time in 1991. The pathological diagnosis was well-differentiated liposarcoma. Thereafter, we resected recurrences in the retroperitoneum in July 2008, with the left half of the colon in June 2011. Then, we resected the pancreatic tails, spleen, accessory spleen, left adrenal gland, left kidney, and part of the diaphragm in October 2012, and part of the diaphragm, descending colon, and jejunum in October 2014. At this time, there were growing recurrences removed from the pancreatic tails. There is no evidence of recurrence after 24 years after the first resection. In this case, it was thought that the factor correlated with long survival was actively resecting recurrences and recognizing high-grade dedifferentiated type liposarcoma at an early stage.


Iris melanocytoma mimicking the Cogan-Reese syndrome with monocular pigment dissemination.
To report a case of iris melanocytoma mimicking the Cogan-Reese syndrome. A 37-year-old woman presented with pigmentary glaucoma in her left eye. There was diffuse pigmentary dispersion in the anterior segment, pedunculated pigmented nodules on the anterior iris surface, mild iris atrophy, and ectropion iridis. Neither intrinsic vasculature nor a sector cataract was found. The angle was open with marked trabecular pigmentation and no anterior synechiae. The intraocular pressure was 30 mmHg with maximum medical treatment and there was glaucomatous optic atrophy. The differential diagnosis included iris pigmented tumor and iridocorneal endothelial syndrome (Cogan-Reese syndrome). An iris biopsy was performed for diagnostic purposes. Histologic diagnosis after evaluation of the specimen was iris melanocytoma. This case presents signs considered quasi-pathognomonic of iridocorneal endothelial syndrome (Cogan-Reese syndrome): glaucoma, mild iris atrophy associated with pedunculated iris nodules, and ectropion iridis. Therefore, iris melanocytoma can present with features that mimic the Cogan-Reese syndrome.


Osteochondral Injuries of the Knee in Pediatric Patients.
Osteochondral injuries in pediatric patients may occur as a result of a traumatic injury or secondary to an osteochondritis dissecans (OCD) lesion. Lateral patella dislocation is a common traumatic cause of osteochondral injury that typically occurs at the medial facet of the patella or at the lateral aspect of the distal femur. Multiple theories have been proposed for the cause of an OCD lesion in the knee, including trauma or repetitive microtrauma, local vascular insufficiency, and family history. The most "classic" location for OCD lesions of the knee is the lateral aspect of the medial femoral condyle of the distal femur. Multiple treatment options are available for both traumatic osteochondral injuries and OCD lesions, with important determining factors of treatment being skeletal maturity of the patient, instability of the fragment, lesion location, and size of the lesion. Nonsurgical management is appropriate in some situations. Surgical options range from simple fragment excision to internal fixation of the fracture fragment to more complex cartilage restoration or replacement procedures. This special focus section will discuss the diagnosis and treatment options for traumatic osteochondral knee injuries, including the subset secondary to juvenile OCD lesions.


IncFIB-4.1 and IncFIB-4.2 Single-Replicon Plasmids: Small Backbones with Large Accessory Regions.
To establish a typing scheme for IncFIB replicon and to dissect genomic features of IncFIB-4.1/4.2 single-replicon plasmids. A total of 146 representative fully sequenced IncFIB-replicon-containing plasmids were selected to construct a phylogenetic tree of repB IncFIB sequences. A collection of nine IncFIB-4.1/4.2 single-replicon plasmids from China were fully sequenced here and compared with the first sequenced IncFIB-4.1/4.2 single-replicon plasmids from GenBank to dissect their genomic diversity. In this study, a repB sequence-based scheme was proposed for grouping IncFIB replicon into seven primary types and further into 70 subtypes. A collection of nine IncFIB-4.1/4.2 single-replicon plasmids were fully sequenced here and compared with the first sequenced IncFIB-4.1/4.2 single-replicon plasmids from GenBank. These 11 plasmids had small backbones and shared only three key backbone markers repB together with its iterons, parABC, and stbD. Each plasmid contained one large accessory region (LAR) inserted into the backbone, and these 11 LARs had significantly distinct profiles of mobile genetic elements (MGEs) and resistance/metabolism gene loci. Antibiotic resistance regions (ARRs; the antibiotic resistance gene-containing genetic elements) were found in seven of these 11 LARs. Besides resistance genes, ARRs carried unit or composite transposons, integrons, and putative resistance units. IncFIB-4.1/4.2 single-replicon plasmids were important vectors of drug resistance genes. This was the first report of three novel MGEs: In1776, Tn6755, and Tn6857. Data presented here provided a deeper insight into diversity and evolution of IncFIB replicon and IncFIB-4.1/4.2 single-replicon plasmids.


Logarithmic relaxation in a colloidal system.
The slow dynamics for a colloidal suspension of particles interacting with a hard-core repulsion complemented by a short-ranged attraction is discussed within the frame of mode-coupling theory for ideal glass transitions for parameter points near a higher-order glass-transition singularity. The solutions of the equations of motion for the density correlation functions are solved for the square-well system in quantitative detail by asymptotic expansion using the distance of the three control parameters-packing fraction, attraction strength and attraction range-from their critical values as small parameters. For given wave vectors, distinguished surfaces in parameter space are identified where the next-to-leading-order contributions for the expansion vanish so that the decay functions exhibit a logarithmic decay over large time intervals. For both coherent and tagged particle dynamics the leading-order logarithmic decay is accessible in the liquid regime for wave vectors of several times the principal peak in the structure factor. The logarithmic decay in the correlation function is manifested in the mean-squared displacement as a subdiffusive power law with an exponent varying sensitively with the control parameters. Shifting parameters through the distinguished surfaces, the correlation functions and the logarithm of the mean-squared displacement considered as functions of the logarithm of the time exhibit a crossover from concave to convex behavior, and a similar scenario is obtained when varying the wave vector.


Effects of C-H stretch excitation on the H+CH4 reaction.
We have investigated the effects of C-H stretching excitation on the H+CH4-->CH3+H2 reaction dynamics using the photo-LOC technique. The CH3 product vibrational state and angular distribution are measured for the reaction of fast H atoms with methane excited in either the antisymmetric stretching fundamental (nu3=1) or first overtone (nu3=2) with a center-of-mass collision energy of Ecoll ranging from 1.52 to 2.20 eV. We find that vibrational excitation of the nu3=1 mode enhances the overall reaction cross section by a factor of 3.0+/-1.5 for Ecoll=1.52 eV, and this enhancement factor is approximately constant over the 1.52-2.20-eV collision energy range. A local-mode description of the CH4 stretching vibration, in which the C-H oscillators are uncoupled, is used to describe the observed state distributions. In this model, the interaction of the incident H atom with either a stretched or an unstretched C-H oscillator determines the vibrational state of the CH3 product. We also compare these results to the similar quantities obtained previously for the Cl+CH4-->CH3+HCl reaction at Ecoll=0.16 eV [Z. H. Kim, H. A. Bechtel, and R. N. Zare, J. Chem. Phys. 117, 3232 (2002); H. A. Bechtel, J. P. Camden, D. J. A. Brown, and R. N. Zare, ibid. 120, 5096 (2004)] in an attempt to elucidate the differences in reactivity for the same initially prepared vibration.


Development and Validation of a Risk Scoring System Derived from Meta-Analyses of Papillary Thyroid Cancer.
The aim of this study was to develop a scoring system to stratify the risk of papillary thyroid cancer (PTC) and to select the proper management. We performed a systematic search of MEDLINE and Embase. Data regarding patients' prognoses were obtained from the included studies. Odds ratios (ORs) with statistical significance were extracted from the publications. To generate a risk scoring system (RSS), ORs were summed (RSS1), and summed after natural-logarithmic transformation (RSS2). RSS1 and RSS2 were compared to the eighth edition of the American Joint Committee on Cancer (AJCC) staging system and the 2015 American Thyroid Association (ATA) guidelines for thyroid nodules and differentiated thyroid carcinoma. Five meta-analyses were eligible for inclusion in the study. Eight variables (sex, tumour size, extrathyroidal extension, BRAF mutation, TERT mutation, histologic subtype, lymph node metastasis, and distant metastasis) were included. RSS1 was the best of the analysed models. We developed and validated a new RSS derived from previous meta-analyses for patients with PTC. This RSS seems to be superior to previously published systems.


Thrombocytosis: age dependent aetiology and analysis of platelet indices for differential diagnosis.
To identify the etiology of thrombocytosis in various age groups and to evaluate the effectiveness of platelet indices in differentiating reactive and clonal thrombocytosis, an observational, prospective review of patients with platelet count of 600 x 10(9)/L or more performed by using coulter counter STKS (Coulter Electronic, Kerfeld, Germany). Extreme thrombocytosis defined as platelet count of 1000 x 10(9)/L or more. Of 1068 patients, 91.8% had reactive and 8.2% had clonal thrombocytosis. Frequent causes of reactive thrombocytosis were infections (44.9%), tissue injury (11.4%) and rebound thrombocytosis (10.2%). Fifty-five patients had extreme thrombocytosis, main aetiologies were secondary and clonal thrombocytosis that seen in 72.7% and 27.3% of cases respectively. Comparison of platelet indices showed; that cases with reactive thrombocytosis had low mean platelet volume and platelet distribution width. We concluded that thrombocytosis could be a response to various physiological and pathological processes. Low MPV and PDW in patients with high platelet counts strongly suggest reactive etiology.


Inhibition of human immunodeficiency virus type 1 replication by nuclear chimeric anti-HIV ribozymes in a human T lymphoblastoid cell line.
Human immunodeficiency virus (HIV) infection represents one of the most challenging systems for gene therapy. Thanks to the extended knowledge of the molecular biology of the HIV life cycle, many different strategies have been developed including transdominant modifications of HIV proteins, RNA decoys, antisense RNA, ribozymes, and intracellular antibody fragments. In this paper, we have tested in a human T lymphoblastoid cell line the antiviral activity of ribozymes specifically designed to co-localize inside the nucleus with the Rev pre-mRNA before it is spliced and transported to the cytoplasm. This result was obtained by inserting the ribozyme in the spliceosomal U1 small nuclear RNA (snRNA) and in a derivative that has perfect complementarity with the 5' splice site of the Rev pre-mRNA. These ribozymes were tested in human T cell clones and were shown to be very efficient in inhibiting viral replication. Not only were the p24 levels in the culture medium drastically reduced but so were the intracellular HIV transcripts. Control disabled ribozymes enabled us to show the specificity of the ribozyme activity. Therefore, these constructs have potential utility for gene therapy of HIV-1 infection.


Significance of Simultaneous Splenic Artery Resection in Left-Sided Portal Hypertension After Pancreaticoduodenectomy with Combined Portal Vein Resection.
In pancreaticoduodenectomy (PD) with resection of portal vein (PV)/superior mesenteric vein (SMV) confluence, the splenic vein (SV) division may cause left-sided portal hypertension (LPH). The 88 pancreatic ductal adenocarcinoma patients who underwent PD with PV/SMV resection after chemoradiotherapy were classified into three groups: both SV and splenic artery (SA) were preserved in Group A (n = 16), SV was divided and SA was preserved in Group B (n = 58), and both SV and SA were divided in Group C (n = 14). We evaluated the influence of resection of SV and/or SA on LPH after PD with resection of PV/SMV confluence. The incidence of postoperative varices in Groups A, B and C was 6.3, 67.2 and 38.5%, respectively (p < 0.001), and variceal bleeding occurred only in Group B (n = 4: 6.8%). In multivariate analysis, Group B was the only significant risk factor for the development of postoperative varices (Groups B vs. A: odds ratio = 39.6, p = 0.001, Groups C vs. A: odds ratio = 8.75, p = 0.066). The platelet count ratio at 6 months after operation comparing to preoperative value was 0.93, 0.73 and 1.09 in Groups A, B and C, respectively (Groups B vs. C: p < 0.05), and spleen volume ratio at 6 months was 1.00, 1.37 and 0.96 in Groups A, B and C, respectively (Groups B vs. A and C: p < 0.01 and p < 0.05). In PD with resection of PV-SMV confluence, the SV division causes LPH, but the concomitant division of SV and SA may attenuate it.


Identification of the HrpS binding site in the hrpL promoter and effect of the RpoN binding site of HrpS on the regulation of the type III secretion system in Erwinia amylovora.
The type III secretion system (T3SS) is a key pathogenicity factor in Erwinia amylovora. Previous studies have demonstrated that the T3SS in E. amylovora is transcriptionally regulated by an RpoN-HrpL sigma factor cascade, which is activated by the bacterial alarmone (p)ppGpp. In this study, the binding site of HrpS, an enhancer binding protein, was identified for the first time in plant-pathogenic bacteria. Complementation of the hrpL mutant with promoter deletion constructs of the hrpL gene and promoter activity analyses using various lengths of the hrpL promoter fused to a promoter-less green fluorescent protein (gfp) reporter gene delineated the upstream region for HrpS binding. Sequence analysis revealed a dyad symmetry sequence between -138 and -125 nucleotides (TGCAA-N4-TTGCA) as the potential HrpS binding site, which is conserved in the promoter of the hrpL gene among plant enterobacterial pathogens. Results of quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and electrophoresis mobility shift assay coupled with site-directed mutagenesis (SDM) analysis showed that the intact dyad symmetry sequence was essential for HrpS binding, full activation of T3SS gene expression and virulence. In addition, the role of the GAYTGA motif (RpoN binding site) of HrpS in the regulation of T3SS gene expression in E. amylovora was characterized by complementation of the hrpS mutant using mutant variants generated by SDM. Results showed that a Y100F substitution of HrpS complemented the hrpS mutant, whereas Y100A and Y101A substitutions did not. These results suggest that tyrosine (Y) and phenylalanine (F) function interchangeably in the conserved GAYTGA motif of HrpS in E. amylovora.


Tetraalkylammonium derivatives as real-time PCR enhancers and stabilizers of the qPCR mixtures containing SYBR Green I.
Tetraalkylammonium (TAA) derivatives have been reported to serve as stabilizers of asymmetrical cyanine dyes in aqueous solutions and to increase the yield and efficiency of polymerase chain reaction (PCR) detected by end-point analysis. In this study, we compared the ability of various TAA derivatives (with alkyl chain ranging from 1 to 5 carbons) and some other compounds to serve as enhancers of real-time PCR based on fluorescence detection from intercalating dye SYBR Green I (SGI). Our data indicate that TAA chlorides and some other TAA derivatives serve as potent enhancers of SGI-monitored real-time PCR. Optimal results were obtained with 10-16 mM tetrapropylammonium chloride. The effect of TAA compounds was dependent on the nature of counter ions present and composition of the reaction mixtures used. Based on measurements of SGI-generated fluorescence signal in the presence of PCR-amplified DNA fragments, oligonucleotide primers and/or various additives, we propose that TAA-derivatives reduce the binding of SGI to oligonucleotide primers and thus enhance primer-template interactions during annealing phase. Furthermore, these compounds serve as stabilizers of SGI-containing PCR mixtures. The combined data indicate that TAA derivatives might be a new class of additives contributing to robustness of real-time PCR monitored by asymmetrical cyanine dye SGI.


Targeting human telomerase RNA component using antisense oligonucleotide induces rapid cell death and increases ATO-induced apoptosis in APL cells.
The impressive advances carried out in designing pharmacological strategies with the aim of telomerase inhibition in cancers emerged a consensus that telomerase-targeted therapies could be exciting prospect in repertoire of future cancer strategies. The results of the present study indicated that targeting telomerase using an oligonucleotide-based molecule against human telomerase RNA template (hTR ASODN) reduced the survival rate of NB4 cells and induced a caspase-3-dependent apoptosis. Our finding was even noticeable in the synergistic experiments, where we found an enhanced reduction in the viability of the cells after short-term treatment with ATO in combination with the inhibitor. The resulting data delineated that short-term treatment of the cells with hTR ASODN either as single agent or in combination with ATO resulted in apoptotic cell death through activation of DNA damage response via up-regulation of p73 and ATM coupled with down-regulation of c-Myc. Moreover, we found that induction of p21 and subsequent disturbance of the death promoter to death repressor genes may contribute to the enhanced growth suppressive effect of the drugs combination. Overall, our findings support the idea that telomerase activity may have pivotal role in attenuating ATO effectiveness and combination of ATO with telomerase inhibitor seems to be a novel promising strategy, which may increase APL cure rates.


[Detection of enterovirus 70 in acute hemorrhagic conjunctivitis by PCR-stringent microplate hybridization method].
The surveillance of acute hemorrhagic conjunctivitis (AHC) caused by enterovirus 70 (EV70) is insufficient because of the difficulties of virus isolation using conventional methods. In this study, reverse transcription-polymerase chain reaction (RT-PCR) and stringent microplate hybridization (SMH) methods were assessed for the detection of EV70 in conjunctival swabs collected from the patients of AHC which broke out in Miyazaki Prefecture in 1990 and Okinawa Prefecture in 1994. Furthermore, with the use of the SMH method, we compared the genetic homogeneity of EV70 detected from the samples collected in 1990 and 1994 to the J670/71 strain isolated approximately 25 years ago. A similar investigation was performed between recent coxsackievirus A24 variant (CA24v) and EH24/70 strain, a standard strain of CA24v that was isolated approximately 25 years ago. As a result, RT-PCR products were detected in 26 of 34 conjunctival swabs collected in Miyazaki Prefecture in 1990. Likewise, RT-PCR products were detected in 9 of 10 conjunctival swabs collected in Okinawa Prefecture in 1994, and these RT-PCR products were all identified as EV70 by SMH method. Such a high level of virus recovery from specimen shows the evidence of usefulness of these techniques. Recent EV70 showed a reaction of about 60% to a probe synthesized with J670/71. Likewise, recent CA24v showed a reaction of about 30% to a probe synthesized with EH24/70. These finding are highly suggestive of the progress of viral mutation.


SARS-CoV-2 Complicated by a Large Hemorrhagic Pericardial Effusion.
Severe acute respiratory syndrome coronavirus (SARS-CoV-2), primarily a respiratory virus, has also presented with cardiac complications including myocarditis, myocardial infarction, and cardiac arrhythmias. Pericardial effusions are also emerging in the literature as a sequel to this viral infection. A case of a 57-year-old Hispanic female with SARS-CoV-2 infection two months prior with worsening dyspnea on exertion who was found to have a large hemorrhagic pericardial effusion with early tamponade physiology was presented in this article. This case highlights the rare complication and the importance of bedside echocardiogram in patients with recent SARS-CoV-2 infection who present with shortness of breath and other signs of pericardial effusion.


Super-Resolution Microscopy of Chromatin.
Since the advent of super-resolution microscopy, countless approaches and studies have been published contributing significantly to our understanding of cellular processes. With the aid of chromatin-specific fluorescence labeling techniques, we are gaining increasing insight into gene regulation and chromatin organization. Combined with super-resolution imaging and data analysis, these labeling techniques enable direct assessment not only of chromatin interactions but also of the function of specific chromatin conformational states.


Single lung transplantation with simultaneous contralateral pneumonectomy for cystic fibrosis.
A 24-year-old man with cystic fibrosis and marked reduction of volume of the left hemithorax caused by skeletal asymmetry and mediastinal shift underwent successful right single lung transplantation with simultaneous left pneumonectomy. Despite significant preoperative microbiologic contamination, it proved possible to sterilize the pneumonectomy space and no airway complications occurred. Good long-term results have been achieved, and the historic assumption that single lung transplantation is unsuitable for patients with septic lung disease is challenged.


Validity of nutritional screening tools for hospitalized children.
Background. Malnutrition in hospitalized children can be prevented if children with risk of malnutrition are identified. Every hospital is recommended to have a standard nutritional screening tool. Numerous simple screening tools have been developed, namely Paediatric Yorkhill Malnutrition Score (PYMS), Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP), and Screening Tool for Risk on Nutritional Status and Growth (STRONG-kids). None has been accepted as a universal tool. Our study aims to determine the best screening tools compared to Subjective Global Nutrition Assessment (SGNA), an assessment tool which is more complex as our gold standard. Methods. This diagnostic study involved 116 patients aged 1-15 years. Three screening tools and SGNA were examined to each subject. Statistical analysis was used to determine sensitivity, specificity, and likelihood ratio (LR) by results from screening tools divided into low and moderate-high risk of malnutrition compared to results from SGNA divided into no and moderate-severe malnutrition. Results. PYMS showed superior agreement to SGNA resulting in sensitivity 95.32%, specificity 76.92%, positive LR 4.13, and negative LR 0.061. STAMP resulted in sensitivity, specificity, positive LR, and negative LR, respectively, as 100%, 11.54%, 1.13, and 0 and STRONG-kids resulted in 100%, 7.7%, 1.083, and 0. Conclusion. PYMS was the most reliable screening tool.


The role of metal components in the cardiovascular effects of PM2.5.
Exposure to ambient fine particulate matter (PM2.5) increases risks for cardiovascular disorders (CVD). However, the mechanisms and components responsible for the effects are poorly understood. Based on our previous murine exposure studies, a translational pilot study was conducted in female residents of Jinchang and Zhangye, China, to test the hypothesis that specific chemical component of PM2.5 is responsible for PM2.5 associated CVD. Daily ambient and personal exposures to PM2.5 and 35 elements were measured in the two cities. A total of 60 healthy nonsmoking adult women residents were recruited for measurements of inflammation biomarkers. In addition, circulating endothelial progenitor cells (CEPCs) were also measured in 20 subjects. The ambient levels of PM2.5 were comparable between Jinchang and Zhangye (47.4 and 54.5 µg/m(3), respectively). However, the levels of nickel, copper, arsenic, and selenium in Jinchang were 82, 26, 12, and 6 fold higher than Zhangye, respectively. The levels of C-reactive protein (3.44 ± 3.46 vs. 1.55 ± 1.13), interleukin-6 (1.65 ± 1.17 vs. 1.09 ± 0.60), and vascular endothelial growth factor (117.6 ± 217.0 vs. 22.7 ± 21.3) were significantly higher in Jinchang. Furthermore, all phenotypes of CEPCs were significantly lower in subjects recruited from Jinchang than those from Zhangye. These results suggest that specific metals may be important components responsible for PM2.5-induced cardiovascular effects and that the reduced capacity of endothelial repair may play a critical role.


Enhanced ouabain resistance gene as a eukaryotic selection marker.
Current selection markers allow selection by antibiotics or fluorescent/magnetic sorting by green fluorescent protein or membrane antigens. Antibiotic selection proceeds on a time scale of weeks, and flourescence-activated cell sorting requires complex equipment and may generate false-positive results when selection is performed too early after transduction with membrane markers. We have characterized an endogenous eukaryotic selection marker, the ouabain resistance gene (Oua(r)), which has the potential for quick and efficient in vitro selection of target cells. The Oua(r) used by us is derived from the rat alpha(1) isoform of Na(+),K(+)-ATPase, where leucine at position 799 is substituted for cysteine by targeted mutagenesis. This mutation confers resistance to more than 1 mM ouabain in vitro. We show that cells transfected with plasmid or transduced with a retrovirus vector encoding Oua(r) can be selected efficiently with ouabain in 48 hr and that a pure population of cells can be obtained. The ouabain resistance gene may be useful as a selection marker in general molecular biology, preclinical, and clinical applications because of its short selection time and also because of the safety of ouabain for human use.


Do calcium channel blockers have any influence on the immunological status of renal graft recipients on ciclosporin therapy?
We have assessed the peripheral distribution of T cells, using the monoclonal antibodies OKT3, OKT4, OKT8 and LEU7 and the proliferative response to phytohaemagglutinin (PHA), in 10 renal transplant recipients. In each patient, the immunological pattern was evaluated twice, both before and after 1 month of calcium antagonist (calcium channel blockers, CaA) treatment. During treatment with CaA, we have observed both a significant decrease in the mitogenic response to PHA and a significant increase in OKT8 cells. Our data support the hypothesis that CaAs per se may have an immunomodulatory effect on T cell distribution independently of changes in ciclosporin (CS) blood levels. These results could also provide a cellular basis for synergism between CS and CaA.


[Verbal fluency tests--application in neuropsychological assessment].
Verbal fluency tests (VFT) have established position in methodology of cognitive functions research. They are used in neuropsychological assessment of neurological and psychiatric diseases. This article's aim is to present current knowledge of the VFT both to clinicians and researchers. It describes models of cognitive processes involved in task performance mainly: semantic memory access and executive functions and. It describes studies on verbal fluency both in healthy and impaired subjects involving neuroimaging discussing neuroanatomical structures involved in task performance. Authors are quite unanimous as to connection between frontal and temporal lobes condition and task performance, but also other cortical and subcortical structures seem to be involved. Methods of qualitative performance analysis and studies applying them are further described. This article brings up also important questions of psychometric and demographic characteristics of the task and limitations arising from the lack of Polish norms of the tool.


Spectrum of and Factors Associated with Eye Disorders among Rheumatoid Arthritis Patients Attending Tertiary Hospital in Uganda.
Ocular morbidities associated with rheumatoid arthritis (RA) have not received much attention in Africa, particularly in sub-Saharan Africa. They are among the commonest (40%) extra-articular organ involvement in RA. If undiagnosed, there is a potential risk of them causing visual impairment or blindness. There is no documented study in Uganda on the magnitude of eye disorders among RA patients. To determine the spectrum of eye disorders and associated factors among patients with RA attending Mulago National Referral Hospital. A hospital based cross-sectional study was conducted among adults with RA attending the rheumatology clinic between July 2021 and September 2021. Clinical and sociodemographic data were collected, and ophthalmologic examinations were performed on all consenting participants. Modified Poisson regression with robust standard error was used to determine factors associated with eye disorders. Overall, 105 patients with RA were enrolled, of which, 53 (50.5%) had eye disorders. The commonest disorder (54.7%, n=29) was dry-eye syndrome. Factors that were significantly associated with eye disorders were age 36-55 years (aPR 1.56, p=0.015), duration of RA >5 years (aPR 1.81, p=0.001), use of hydroxychloroquine >5 years (aPR 1.77, p=0.041), dose of oral steroids >10 mg/day (aPR 1.49, p=0.034), and history of both diabetes and hypertension (aPR 1.87, p=0.014). The prevalence of eye disorders among patients with RA was high, with the commonest being dry-eye syndrome. We recommend that ocular examinations be performed on every patient at the time of RA diagnosis for early detection of eye disorders.


Mean Duration of Mechanical Ventilation among Newborns Admitted to the Neonatal Intensive Care Unit in a Tertiary Care Centre: A Descriptive Cross-sectional Study.
Neonatal deaths account for the majority of deaths in the first year of life. Life-threatening apnoea or cardiovascular collapse needs cardiopulmonary resuscitation. Technological advancements, such as the administration of antepartum steroids, replacement of surfactants, nasal continuous positive airway pressure, and mechanical ventilation have led to improved neonatal survival, especially for premature neonates. The aim of this study was to find out the mean duration of mechanical ventilation among newborns admitted to the Neonatal Intensive Care Unit in a tertiary care centre. A descriptive cross-sectional study was conducted from 15 November 2020 to 15 April 2021 in a tertiary care centre. Ethical approval was taken from Institutional Review Committee (Reference number: F-NMC|504|076|077). The neonates of gestational age between 27-37 weeks of gestation admitted to the Neonatal care unit were included in the study. Neonates with birth weight <500 g and those babies having major, surgically uncorrectable lethal anomalies were excluded from the study. Convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Among 86 neonates, the mean duration of mechanical ventilation was 2.19±1.42 days. The mean weight of neonates was 2.63±0.81 kg. A total of 71 (82.56%) were male and 15 (17.44%) were female. The mean duration of mechanical ventilation among newborns admitted to the neonatal intensive care unit in a tertiary care centre was lower than in other studies conducted in similar settings. mechanical ventilation; neonatal death; neonatal intensive care unit; neonate.


Laser micromachined hybrid open/paper microfluidic chips.
Paper-based microfluidics are an increasingly popular alternative to devices with conventional open channel geometries. The low cost of fabrication and the absence of external instrumentation needed to drive paper microchannels make them especially well suited for medical diagnostics in resource-limited settings. Despite the advantages of paper microfluidics, many assays performed using conventional open channel microfluidics are challenging to translate onto paper, such as bead, emulsion, and cell-based assays. To overcome this challenge, we have developed a hybrid open-channel/paper channel microfluidic device. In this design, wick-driven paper channels control the flow rates within conventional microfluidics. We fabricate these hybrid chips using laser-micromachined polymer sheets and filter paper. In contrast to previous efforts that utilized external, macroscopic paper-based pumps, we integrated micro-scale paper and open channels onto a single chip to control multiple open channels and control complex laminar flow-pattern within individual channels. We demonstrated that flow patterns within the open channels can be quantitatively controlled by modulating the geometry of the paper channels, and that these flow rates agree with Darcy's law. The utility of these hybrid chips, for applications such as bead-, cell-, or emulsion-based assays, was demonstrated by constructing a hybrid chip that hydrodynamically focused micrometer-sized polystyrene beads stably for >10 min, as well as cells, without external instrumentation to drive fluid flow.


A novel effect of bismuth ions: selective inhibition of the biological activity of glycine-extended gastrin.
Although bismuth salts have been used for over two centuries for the treatment of various gastrointestinal disorders, the mechanism of their therapeutic action remains controversial. Because gastrins bind two trivalent ferric ions with high affinity, and because ferric ions are essential for the biological activity of glycine-extended gastrin 17, we have investigated the hypothesis that trivalent bismuth ions influence the biological activity of gastrins. Binding of bismuth ions to gastrins was measured by fluorescence quenching and NMR spectroscopy. The effects of bismuth ions on gastrin-stimulated biological activities were measured in inositol phosphate, cell proliferation, and cell migration assays. Fluorescence quenching experiments indicated that both glycine-extended and amidated gastrin 17 bound two bismuth ions. The NMR spectral changes observed on addition of bismuth ions revealed that Glu-7 acted as a ligand at the first bismuth ion binding site. In the presence of bismuth ions the ability of glycine-extended gastrin 17 to stimulate inositol phosphate production, cell proliferation, and cell migration was markedly reduced. In contrast, bismuth ions had little effect on the affinity of the CCK-2 receptor for amidated gastrin 17, or on the stimulation of inositol phosphate production by amidated gastrin 17. We conclude that bismuth ions may act, at least in part, by blocking the effects of glycine-extended gastrin 17 on cell proliferation and cell migration in the gastrointestinal tract. This is the first report of a specific inhibitory effect of bismuth ions on the action of a gastrointestinal hormone.


Occult Head Injury in Children Less Than 2 Years With Suspected Child Abuse in the Emergency Department.
This study aims to determine the frequency of clinically significant findings requiring emergent neurosurgical intervention on computed tomography (CT) in neurologically intact children admitted to the hospital with suspected abuse. This was a retrospective review of neurologically stable children (0-24 months) in whom both skeletal survey and CT head were performed for child abuse evaluation from 2000 to 2011. A total of 132 patients met inclusion criteria (mean age, 7.6 mo; 55% male, 52% Caucasian, and 34% African-American). Computed tomography scans demonstrated occult head injury in 5%; none required neurosurgical intervention or had any neurological deterioration. Average length of stay was 4 days, with average time to CT scan being 12.8 hours from triage, and average time to magnetic resonance imaging (MRI) scan of 70.5 hours. Five MRIs were performed, and 4 had identical results on CT scan. No clinically significant brain injury (requiring intervention) was seen in this cohort. These findings support delaying imaging in neurologically intact children to obtain MRI after hospital admission, thus, limiting radiation exposure.


[Therapeutic catheterization in adults with congenital cardiopathy].
We report our results with therapeutic cardiac catheterization in adult patients with four of the most frequent congenital heart diseases. 1) Valvular pulmonary stenosis. We treated 20 patients older than 15 years of age and we concluded that anatomy of the valve is the most important variable related to immediate and long-term results. 2) Aortic coarctation. In a group of 54 patients, 32 treated with angioplasty alone and 22 with stent, we concluded that the main determinant for a good long-term result is the residual gradient, which is related to the coarctation anatomy and the use of stent. 3) Patent ductus arteriosus. In 17 adult patients, the ductus was occluded with coils in 5 and with the Amplatzer duct occluder in 12 with complete occlusion of the ductus in all cases followed for a mean period of 18 months and without complications. 4) Atrial septal defect. We treated 39 adult patients using the Amplatzer septal occluder with good results.


Induction of nucleoside phosphorylase in Enterobacter aerogenes and enzymatic synthesis of adenine arabinoside.
Nucleoside phosphorylases (NPases) were found to be induced in Enterobacter aerogenes DGO-04, and cytidine and cytidine 5'-monophosphate (CMP) were the best inducers. Five mmol/L to fifteen mmol/L cytidine or CMP could distinctly increase the activities of purine nucleoside phosphorylase (PNPase), uridine phosphorylase (UPase) and thymidine phosphorylase (TPase) when they were added into medium from 0 to 8 h. In the process of enzymatic synthesis of adenine arabinoside from adenine and uracil arabinoside with wet cells of Enterobacter aerogenes DGO-04 induced by cytidine or CMP, the reaction time could be shortened from 36 to 6 h. After enzymatic reaction the activity of NPase in the cells induced remained higher than that in the cells uninduced.


Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry.
Most genome-wide association studies (GWAS) for lipid traits focus on the separate analysis of lipid traits. Moreover, there are limited GWASs evaluating the genetic variants associated with multiple lipid traits in African ancestry. To further identify and localize loci with pleiotropic effects on lipid traits, we conducted a genome-wide meta-analysis, multi-trait analysis of GWAS (MTAG), and multi-trait fine-mapping (flashfm) in 125,000 individuals of African ancestry. Our meta-analysis and MTAG identified four and 14 novel loci associated with lipid traits, respectively. flashfm yielded an 18% mean reduction in the 99% credible set size compared to single-trait fine-mapping with JAM. Moreover, we identified more genetic variants with a posterior probability of causality >0.9 with flashfm than with JAM. In conclusion, we identified additional novel loci associated with lipid traits, and flashfm reduced the 99% credible set size to identify causal genetic variants associated with multiple lipid traits in African ancestry.


An amino acids mixture improves the hepatotoxicity induced by acetaminophen in mice.
Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The aim of this study was to evaluate the protective role of DDM-GSH, a mixture of L-cysteine, L-methionine, and L-serine in a weight ratio of 2 : 1 : 1, in comparison to N-acetylcysteine (NAC), against acetaminophen- (APAP-) induced hepatotoxicity in mice. Toxicity was induced in mice by the intraperitoneal (ip) administration of low dose (2 mmol/kg) or high dose (8 mmol/kg) of APAP. DDM-GSH (0.4 to 1.6 mmol/kg) was given ip to mice 1 h before the APAP administration. The same was done with NAC (0.9 to 3.6 mmol/kg), the standard antidote of APAP toxicity. Mice were sacrificed 8 h after the APAP injection to determine liver weight, serum alanine aminotransferase (ALT), and total glutathione (GSH) depletion and malondialdehyde (MDA) accumulation in liver tissues. DDM-GSH improved mouse survival rates better than NAC against a high dose of APAP. Moreover, DDM-GSH significantly reduced in a dose-dependent manner not only APAP-induced increases of ALT but also APAP-induced hepatic GSH depletion and MDA accumulation. Our results suggest that DDM-GSH may be more potent than NAC in protecting the liver from APAP-induced liver injury.


[Combination chemotherapy with vincristine, melphalan, CCNA, cyclophosphamide, prednisone in myeloma].
The authors report the results of a prospective, multi-centre trial involving 87 patients with previously untreated myeloma who were treated by combination chemotherapy consisting of melphalan, cyclophosphamide, CCNU, prednisone and vincristine. 83.1% of patients had a high tumour mass (stage III on Durie and Salmon's classification). The response to treatment could be evaluated in 76 patients and 70% were found to respond. The median actuarial survival of the whole population is 30 months. The survival is significantly longer (p less than 0.001) in responders (median 40 months) than in non-responders (median: 17 months); the survival is significantly shorter (p less than 0.01) in subjects with renal failure (median: 10 months) than in subjects without renal failure (median: 36 months). This treatment is sufficiently well tolerated to be administered on an outpatient basis. One case of acute monoblastic leukaemia was observed. These results are similar to those reported in the literature.


Immune reactivity of RBL-3, a nonproducer leukemia induced by Rauscher murine leukemia virus in C57BL/6 mice.
A cultured line of RBL-3 leukemia, induced by Rauscher murine leukemia virus (R-MuLV) in C57BL/6 mice, was found to be a virus nonproducer. An NB tropic virus indistinguishable from R-MuLV, however, was recovered after treatment with 5-iodo-2'-deoxyuridine (optimal concentration, 200 microgram/ml). Dexamethasone treatment slightly boosted the production of the activated virus but did not by itself activate the virus. RBL-3 cells were found to have Fc receptors but no surface immunoglobulin or Thy 1.2 antigen. RBL-3 cells exhibited the Friend-Moloney-Rauscher virus-specific transplantation antigen as shown by its immunosensitivity and immunogenicity in tumor rejection experiments. Crude membrane and crude soluble antigen preparations obtained from RBL-3 cell membranes retained the capacity to induce tumor rejection.


Bisindolylmaleimide VIII enhances DR5-mediated apoptosis through the MKK4/JNK/p38 kinase and the mitochondrial pathways.
Bisindolylmaleimide VIII (Bis VIII) has been previously shown to enhance Fas-mediated apoptosis through a protein kinase C-independent mechanism. In the present study, we examined the effect of Bis VIII on apoptosis induced by DR5 (TRAIL-R2), using an agonistic anti-human DR5 monoclonal antibody, TRA-8. Our results demonstrated that Bis VIII was able to enhance the apoptosis-inducing activity of TRA-8 both in vitro and in vivo. The combination of TRA-8 and Bis VIII led to a synergistic and sustained activation of the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase, which was mediated by MAPK kinase 4 and was caspase-8-dependent. The mitochondrial pathway is involved in the synergistic induction of apoptosis by Bis VIII and TRA-8. Bis VIII alone induced the loss of mitochondrial membrane potential in a caspase-independent fashion without subsequent release of cytochrome c. However, in the presence of Bis VIII, TRA-8 induced more profound loss of mitochondrial membrane potential and release of cytochrome c. These results suggest that the enhanced and persistent activation of the JNK/p38 and the decreased mitochondrial membrane potential play a crucial role in synergistic induction of the death receptor-mediated apoptosis by Bis VIII. The unique ability of Bis VIII to enhance DR5-mediated apoptosis signal transduction discloses a potential utility of this compound in combination with anti-DR5 antibody in cancer therapy.


Improved standards for laboratory animals?
In February 1993, Judge Charles R. Richey of the United States District Court issued a summary judgment in the case of Animal Legal Defense Fund, et al. v. The Secretary of Agriculture, et al. The decision, which was in favor of the Animal Legal Defense Fund, requires the U.S. Department of Agriculture to withdraw its current regulations governing exercise for dogs and the psychological well-being of nonhuman primates used for biomedical research and to issue new regulations containing only minimum, measurable standards. Both plaintiffs and defendants contended that they were seeking the best interests of the laboratory animals. The issue at stake is whether animals are better protected if the government establishes limited minimal standards or is allowed to require institutions to provide additional standards, which will be judged on the basis of their effectiveness in maintaining healthy animals. The Court avoided this dispute, however, by placing primary emphasis on applying the Administrative Procedures Act and stating that it was merely interpreting the "plain meaning" of the Animal Welfare Act, as amended. In this article, arguments are presented for interpreting the law in a far more flexible way than Judge Richey did. The conclusion is also reached that there were no winners in the Animal Legal Defense Fund case and that the real losers are the laboratory animals.


[Spectral analysis of the variations in heart rate and cardiac activation on waking up in sleepwalking].
In sleepwalking, a disorder that is characterised by partial waking, the subject experiences an alteration of the microstructure of sleep that can affect autonomous activity during sleep and the waking state. In order to evaluate any possible upset in the regulation of autonomous functioning in sleepwalkers during sleep and the waking state, we conducted a spectral analysis of their heart rate variability (HRV) during both sleep and the waking state. Spectral analysis of HRV was conducted in the group of 10 sleepwalkers and 10 normal controls during sleep and during the waking state in both the horizontal and vertical positions. Their pattern of cardiac activation was also analysed during different types of arousal. There were no differences between the group of sleepwalkers and the control group in the parameters used in the spectral analysis of HRV during sleep and in the horizontal position during the waking state. Sleepwalkers showed a greater shift in the sympathovagal balance in favour of sympathetic activity, as a response to standing. During the 5-minute sequences immediately before the start of pathological arousal in sleepwalkers, the total energy in the spectral analysis of HRV was seen to increase. No differences were found between the patterns of cardiac activation displayed by the groups of patients and normal subjects during several different types of arousal. Autonomous reactivity was seen to be altered as a response to the orthostatic load in sleepwalkers, which could be the consequence of the instability of these patients' sleep. The increase in the total energy in the spectral analysis of HRV immediately before pathological arousal during NREM 4 sleep in sleepwalkers suggests that autonomous activation precedes cortical arousal.


Effects of long-term simvastatin treatment on testicular and adrenal steroidogenesis in hypercholesterolemic patients.
Simvastatin is an inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in the synthesis of cholesterol, recently introduced in the therapy of hypercholesterolemic patients. Cholesterol is the precursor of the biosynthesis of steroid hormones; thus, a reduction of the availability of cholesterol in the adrenal and testicular cells may reduce the synthesis of corticosteroids and androgens. To establish whether chronic therapy with simvastatin interferes with the integrity of the hypothalamic-pituitary-adrenal axis and with the adrenal and testicular reserve, we administered simvastatin orally in a single-day 10 mg dose for 6 months in 8 mildly hypercholesterolemic male patients. At weeks 0, 6 and 24 of treatment we evaluated the lipids, the activity of the hypothalamic-pituitary-adrenal axis by means of the Corticotropin-Releasing Hormone (CRH) test, the adrenal reserve by means of the Corticotropin rapid test and, finally, the testicular reserve by means of the Human Chorionic Gonadotropin (HCG) test. Total cholesterol and LDL-cholesterol were significantly reduced by Simvastatin, while the HDL-cholesterol and triglycerides did not change significantly. The hormonal responses to CRH, ACTH and HCG tests at weeks 6 and 24 of treatment were comparable to those obtained in basal conditions. We conclude that Simvastatin, while effective in reducing total and LDL-cholesterol in hypercholesterolemic male patients, did not interfere with hypothalamic-pituitary-adrenal axis activity or with basal and stimulated adrenal and testicular steroidogenesis.


Emerging photon technologies for chemical dynamics.
I discuss the recent developments concerning emerging ultrafast sources of short wavelength radiation, as well as the new methods they generate. I then dwell on a few examples of recent results and the way the new sources will bring major advancements in our understanding of fundamental chemical dynamics.


Scientific basis for an air quality standard on benzene.
The European Union is developing a comprehensive programme of air quality standards (AQS), including benzene. For that purpose, CONCAWE has reviewed the data to support a scientifically derived AQS for benzene and has concluded that 30 ppb (96 micrograms/m3) as an annual TWA could be used as a basis. The conclusion is based on the NOAEL of acute myelocytic and monocytic leukaemia (AMML), which is considered to be the critical effect, derived from an occupational epidemiological mortality study, to which adjustment factors were applied.


Semicontinuous diffusion fermentation of fodder beets for fuel ethanol and cubed protein feed production.
A novel, semicontinuous diffusion fermentation system was used to produce fuel ethanol and a cubed protein feed (CPF) from fodder beets at an intermediate scale. In the process, fodder beet cubes were augered diagonally upward against a flow of 0.26N H(2)SO(4) and yeast in a tubular fermentor. Exiting one end of the fermentor was CPF, while fermented beer [6-9% (v/v) ethanol] exited the other end. Retention times for beer and CPF were 264 and 72 h, respectively. Contamination was controlled by maintaining the fermentation pH between 2.1 and 2.6 using H(2)SO(4). Production costs for a greatly scaled-up (times 1400) conceptual version of this system (using a continuous rather than a semicontinuous processing mode) were projected by calculation to be $0.529/L for 95% ethanol (net of a $0.112/L credit for CPF). The calculated energy balance (energy output-energy input ratio) was estimated to be 3.04. In calculating the energy balance, the output energy of the CPF and input energy for growing the fodder beets were not included. A design for the scaled-up plant is provided.


LaeA, a regulator of morphogenetic fungal virulence factors.
Opportunistic animal and plant pathogens, well represented by the genus Aspergillus, have evolved unique mechanisms to adapt to and avoid host defenses. Aspergillus fumigatus, an increasingly serious pathogen owing to expanding numbers of immunocompromised patients, causes the majority of human infections; however, an inability to identify bona fide virulence factors has impeded therapeutic advances. We show that an A. fumigatus mutation in a developmentally expressed transcriptional regulator (deltalaeA) coordinating morphological and chemical differentiation reduces virulence in a murine model; impaired virulence is associated with decreased levels of pulmonary gliotoxin and multiple changes in conidial and hyphal susceptibility to host phagocytes ex vivo. LaeA, a conserved protein in filamentous fungi, is a developmental regulator of virulence genes and, possibly, the first antimicrobial target specific to filamentous fungi that are pathogenic to plants and animals.


Exposure-Response Analysis and Mechanism of Ginkgolide B's Neuroprotective Effect in Acute Cerebral Ischemia/Reperfusion Stage in Rat.
Ginkgolide B (GKB) is a well-established neuroprotectant for acute ischemia stroke. However, its cerebral exposure and real-time response remain elusive in acute ischemia/reperfusion stage, and it hinders its usage in therapeutic window of ischemia stroke. Therefore, we investigate the exposure-response relationship of GKB (10 mg/kg, intravenously (i.v.)) as well as its neuroprotective mechanism in acute ischemia/reperfusion rats. Cerebral and plasma exposure of GKB is comparatively explored in both of normal rats and acute ischemia/reperfusion rats. Correspondingly, neurological function and brain jury indexes were assessed at each time point, and superoxide dismutase (SOD), malondialdehyde (MDA), platelet activator factor (PAF) and thromboxane A2 (TXA2) are indexed as pharmacological response to GKB. Exposure-response relationships are analyzed by using linear regression. Additionally, cerebral expressions of proteins in PAF-regulated pathways are tested at each time point. Results show cerebral and plasma concentrations of GKB are much higher in acute ischemia/reperfusion rats than those in normal rats. Cerebral infarction, neurological function (NF) score, abnormal PAF and excessive MDA are significantly alleviated in 24 h after GKB injection, and PAF is reduced in exposure-response manner with significant concentration-response relationship (R2 = 0.9123). Regarding downstream proteins in intracellular PAF-regulated pathway, GKB progressively inhibits Bax, Caspase-3, p-p65 and p-IKK, while gradually restoring LC3B, p62 and p-mammalian target of rapamycin (mTOR) to the basic level within 24 h. Conclusively, GKB exhibits greater cerebral exposure in acute ischemia/reperfusion rats and neuroprotective effect through reducing PAF in exposure-response manner and mediating PAF-regulated intracellular signaling pathways. Our finding highlights clinical implications of GKB in therapeutic time window of ischemic stroke.


Apparent ileal digestibility of amino acids and the digestible and metabolizable energy content of high-oil corn varieties and its effects on growth performance of pigs.
Two experiments were conducted to compare the nutritional value of normal and high-oil corn for pigs. The normal corn and the two varieties (high-oil corns A and B) of high-oil corn contained 4.41, 7.35 and 8.86% ether extract, on DM basis, respectively. In experiment 1, six non-littermate crossbred barrows (37.8 +/- 1.3 kg BW) were fitted with ileal T-cannulas and used in a double replicated Latin Square digestion trial. Three diets were formulated containing 96.6% of one of the three varieties of corn as the only protein source. Chromic oxide (0.4%) was added as a digestibility marker. Additional vitamins and minerals were added to meet requirements. The digestible energy concentrations for normal corn and high-oil corn A and B were 16.53, 16.99 and 17.07 MJ/kg while the metabolizable energy values were 15.82, 16.32 and 16.36 MJ/kg, on DM basis, respectively. The ileal amino acid digestibility of high-oil corn was generally higher than that of normal corn with significant differences being observed for the essential amino acids isoleucine and phenylalanine. In experiment 2, 96 pigs (8.01 +/- 0.14 kg BW) were used to evaluate four diets in a 2 x 2 factorial design conducted over a 35-day period. Corn variety (high-oil vs. normal corn) and nutrient density (high content of protein and ME vs. low content of protein and ME) were set as the two main effects. During the first 14 days, pigs fed high-oil corn diets consumed more feed and tended to get higher daily gain than pigs fed normal corn. Over the entire 35-day experiment, increasing dietary nutrient density increased daily gain and tended to increase feed conversion, while variety of corn had no significant effects on performance. Overall, the present results indicate that the energy concentration and ileal amino acid digestibility of high-oil corn varieties were equal or superior to those in normal corn and therefore they should be able to be effectively utilized in diets fed to swine.


[Hormonal contraceptives and cardiovascular risk. Results of an East German multicenter case control study].
Case control studies of oral contraceptives in the literature proved an increasing risk of cardiovascular diseases ranged from 2 to 6. In the presented GDR-case-control-study 425 women with cardiovascular diseases and 1,275 controls without cardiovascular diseases have been entered. Cases and controls were examined in ten centers. We found no elevated risk for ischemic heart disease, cerebrovascular disease, and hypertonic heart disease in oral contraceptive users. The risk did not depend on age, type of oral hormonal contraceptive, and duration of use. There was only a statistical significant increase in the estimated relative risk of 2.05 in venous thrombosis and thrombophlebitis. Of course, prudent medical practice requires that a possible risk of certain cardiovascular events during hormonal contraceptive use must be taken into account when weighting the risks and benefits of each patient's contraceptive choices. Further studies are needed.


Cell Phone Use and Happiness Among Chinese Older Adults: Does Rural/Urban Residence Status Matter?
This study explores the relationship between cell phone use and self-reported happiness among older adults in Mainland China and whether rural/urban residence status moderates this relationship. The analysis is based on a sample of 6,952 respondents over the age of 60, from the 2010 wave of China Family Panel Studies. Findings show that using own cell phone is positively associated with self-reported happiness among Chinese older adults (odds ratio [ OR] = 1.283, p < .001). This relationship remains for respondents residing in rural areas ( OR = 1.616, p < .01) but not for their urban counterparts. Findings reflect on how the happiness of Chinese older adults has been affected by a growing shift in the traditional family values due to the unprecedented economic growth. Results also highlight the disparities between state support for older adults in rural and urban areas as well as the necessity to develop relevant policies to improve the subjective well-being of China's rapidly growing population of older adults.


Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease.
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the history of this debilitating lung condition. Associated health care utilization and morbidity are high, and many patients require supplemental oxygen or ventilatory support. The last 2 decades have seen a substantial increase in our understanding of the best way to manage the respiratory failure suffered by many patients during this high-risk period. This review article examines the evidence underlying supplemental oxygen therapy during exacerbations of COPD. We first discuss the epidemiology and pathophysiology of respiratory failure in COPD during exacerbations. The rationale and evidence underlying oxygen therapy, including the risks when administered inappropriately, are then discussed, along with further strategies for ventilatory support. We also review current recommendations for best practice, including methods for improving oxygen provision in the future.


Beta cells arise from glucose transporter type 2 (Glut2)-expressing epithelial cells of the developing rat pancreas.
We observe Glut2 protein in day 11 (E11) rat embryos in an endodermal domain containing the pancreatic primordium. Glut2 expression continues as the endodermal epithelium evaginates into the surrounding mesenchyme to form the pancreatic buds. Cells of the dorsal and ventral pancreatic buds maintain Glut2 expression as the epithelium grows and branches to form ducts. As acini form at the ends of the ducts, acinar cells cease Glut2 expression. Insulin protein is first detected in small clusters at the interface between pancreatic epithelium and mesenchyme. These clusters disperse into the interstitial tissue between E13 and E17. At E17 a distinct, larger population of insulin-expressing cells arises in the Glut2-expressing ductal network. Insulin- and Glut2-coexpressing cells then appear to segregate into large aggregates to form the beta cells of the islets of Langerhans. These observations support the hypothesis that two biologically distinct populations of insulin-expressing cells arise during pancreas formation.


Surgical Treatment of Enchondromas of the Hand During Childhood in Ollier Disease.
The objective of the present study was to evaluate the outcome of surgical treatment of hand lesions in Ollier disease (OD) carried out during childhood. A retrospective review was carried out of 10 pediatric patients with hand involvement of OD, who had undergone surgery for metacarpal or phalangeal enchondromas. The technique comprised curettage and cortical bone reconstruction with corticoplasty, to restore a near-normal phalangeal volume. The range of finger motion (pulp-to-palm distance), the shortened Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire score, cosmetic improvement, radiological findings (according to Tordai's classification), and recurrence were recorded after a mean follow-up of 7.5 years (range, 4-11.3 years). The mean age at surgery was 10.7 years (range, 6-14 years). Curettage was performed on 35 enchondromas, and 9 cavities were filled with a bone graft. The mean pulp-to-palm distance was significantly lower after surgery (from 1.5 cm to 0.25 cm; P < .05). The mean QuickDASH score was 3.84 (range, 0-11.4). A marked cosmetic improvement was noted for 83% of the hands. Three enchondromas recurred in 1 patient, requiring a second curettage. Fifty-seven percent of the cavities were completely filled with bone (Tordai stage 1) at last follow-up. The outcome did not depend on the presence or absence of a bone graft. Our results suggest that early surgical treatment comprising curettage and corticoplasty leads to good clinical, cosmetic, and radiological outcomes. Early surgical treatment of well-developed and/or symptomatic enchondromas of the hand in OD should be considered. Therapeutic V.


Two-photon fluorescence microscopy of laurdan generalized polarization domains in model and natural membranes.
Two-photon excitation microscopy shows coexisting regions of different generalized polarization (GP) in phospholipid vesicles, in red blood cells, in a renal tubular cell line, and in purified renal brushborder and basolateral membranes labeled with the fluorescent probe laurdan. The GP function measures the relative water content of the membrane. In the present study we discuss images obtained with polarized laser excitation, which selects different molecular orientations of the lipid bilayer corresponding to different spatial regions. The GP distribution in the gel-phase vesicles is relatively narrow, whereas the GP distribution in the liquid-crystalline phase vesicles (DOPC and DLPC) is broad. Analysis of images obtained with polarized excitation of the liquid-crystalline phase vesicles leads to the conclusion that coexisting regions of different GP must have dimensions smaller than the microscope resolution (approximately 200 nm radially and 600 nm axially). Vesicles of an equimolar mixture of DOPC and DPPC show coexisting rigid and fluid domains (high GP and low GP), but the rigid domains, which are preferentially excited by polarized light, have GP values lower than the pure gel-phase domains. Cholesterol strongly modifies the domain morphology. In the presence of 30 mol% cholesterol, the broad GP distribution of the DOPC/DPPC equimolar sample becomes narrower. The sample is still very heterogeneous, as demonstrated by the separations of GP disjoined regions, which are the result of photoselection of regions of different lipid orientation. In intact red blood cells, microscopic regions of different GP can be resolved, whereas in the renal cells GP domains have dimensions smaller than the microscope resolution. Preparations of renal apical brush border membranes and basolateral membranes show well-resolved GP domains, which may result from a different local orientation, or the domains may reflect a real heterogeneity of these membranes.


Tenascin-W is a novel marker for activated tumor stroma in low-grade human breast cancer and influences cell behavior.
This is the first report about human tenascin-W, the fourth and final member of the extracellular matrix protein family of tenascins. Sixty-three human breast tumor extracts were analyzed by Western blotting for the presence of tenascin-W and compared with tenascin-C, an established marker of tumor stroma. Interestingly, we found tenascin-W expression in the majority of the tumor tissues, but no detectable expression in the normal mammary parenchyma. Eighty-one percent of the breast tumor samples were tenascin-W positive and 86% showed expression of tenascin-C. However, tenascin-W and tenascin-C amounts varied greatly between tumors and some contained either tenascin-W or tenascin-C exclusively, indicating independent mechanisms regulating their expression. Although there was no difference between high- or low-grade tumors with respect to the presence of tenascin-C, tenascin-W was more prominent in low-grade tumors. For 42 of the breast cancer tissues, a frozen tumor microarray was available to confirm the Western blot data by immunohistochemistry. Similar to tenascin-C, tenascin-W was detected in the tumor stroma. Fibroblasts adhered to tenascin-W in a beta(1) integrin-dependent manner and spread with a distinctive morphology under conditions where they remained round on tenascin-C. CHOB2 cells expressing alpha(v)beta(1) or alpha4beta(1) integrins were able to spread on tenascin-W. Furthermore, addition of tenascin-W to the culture medium increased migration of breast cancer cells toward a fibronectin substratum in vitro. These data imply that tenascin-W expression in the activated tumor stroma facilitates tumorigenesis by supporting the migratory behavior of breast cancer cells.


The development of an observational coding scheme to assess transgender and nonbinary clients' reported minority stress experiences.
Trans and nonbinary individuals experience high rates of identity-based stigma and stress (minority stress) in U.S. society. Despite research empirically linking minority stress with adverse mental health outcomes, the extent to which minority stress experiences are discussed in psychotherapy and how therapists respond is unknown. The primary aim of the present study was to develop and test an observational coding scheme, the Minority Stress Experiences and Interactions (MSEI) scheme. With this scheme, observational data from psychotherapy sessions with 19 transgender and nonbinary adult psychotherapy client participants were coded to provide pilot data for the initial development of the MSEI coding scheme. A total of 19 clients' entire 50-min psychotherapy sessions were coded over 3 phases of psychotherapy: beginning (Session 1), middle (Session 2), and end (Session 10/11). Results indicate that the MSEI scheme was reliable for most codes. Codes revealed that all (N = 19; 100%) clients in the study reported at least 1 minority stress event (MSE) over the course of the 3 sessions, with the mean number of MSEs being 7 per client. The most frequent proximal stressor reported by clients was related to internalized stigma and the most frequent distal stressor reported by clients was prejudice. A total of 2 clients' clinical exchanges with their therapists centered on MSEs are highlighted to demonstrate the nuance of how MSEs are discussed in session, specifically regarding multiple minority identities. Implications for the current study include the need for therapist training regarding minority stress interventions and attention to power and oppression within sessions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).