Movement artefacts and MR BOLD signal increase during different paradigms for mapping the sensorimotor cortex.
The authors evaluated the impact of motion artefacts on presurgical mapping of the sensorimotor cortex with functional magnetic resonance imaging (fMRI). Different mapping paradigms were compared with regard to the frequency of motion artefacts and the resulting signal increase. 94 surgical candidates with mass lesions near the central region were investigated using BOLD(1)-contrast T2(*) weighted multislice multi-echo EPI gradient echo sequences on a 1,5 T Philips Gyroscan. Three functional paradigms were performed: a) repetitive self-paced clenching of the hand to a fist (68 runs); b) repetitive finger-to-thumb opposition (46 runs); c) sensory stimulation by repetitive brushing of the palm (15 runs). Task-related haemodynamic changes were identified by statistical analysis with the Kolmogorov-Smirnov-test. MR signal increase in percent was calculated for each of the paradigms. Motion artefacts were rated on a scale from 1 to 3. Severe motion artefacts occurred in 8 hand clenching runs and in 2 finger opposition runs. Artefacts were more pronounced in hand clenching than in finger opposition. There were no motion artefacts in any of the sensory stimulation runs. Concerning the percent MR signal change there was no significant difference between hand clenching and finger opposition (T-test: p>0,5) but a highly significant difference (p<0,0001) between both motor tasks and the sensory paradigm (hand clenching: 2.68+/-0.75; finger opposition: 2.76+/-0.79; sensory stimulation: 1.72+/-0.65). Sensory stimulation causes by far less artefacts than motor paradigms but it also has to be considered less sensitive as it produces a smaller MR signal increase. Therefore in presurgical evaluation sensory stimulation should be kept in reserve for cases in whom motion artefacts are very likely to occur, i.e. patients with severe forms of paresis.


Transcriptome-based variant calling and aberrant mRNA discovery enhance diagnostic efficiency for neuromuscular diseases.
Whole-exome sequencing-based diagnosis of rare diseases typically yields 40%-50% of success rate. Precise diagnosis of the patients with neuromuscular disorders (NMDs) has been hampered by locus heterogeneity or phenotypic heterogeneity. We evaluated the utility of transcriptome sequencing as an independent approach in diagnosing NMDs. The RNA sequencing (RNA-Seq) of muscle tissues from 117 Korean patients with suspected Mendelian NMD was performed to evaluate the ability to detect pathogenic variants. Aberrant splicing and CNVs were inspected to identify additional causal genetic factors for NMD. Aberrant splicing events in Dystrophin (DMD) were investigated by using antisense oligonucleotides (ASOs). A non-negative matrix factorisation analysis of the transcriptome data followed by cell type deconvolution was performed to cluster samples by expression-based signatures and identify cluster-specific gene ontologies. Our pipeline called 38.1% of pathogenic variants exclusively from the muscle transcriptomes, demonstrating a higher diagnostic rate than that achieved via exome analysis (34.9%). The discovery of variants causing aberrant splicing allowed the application of ASOs to the patient-derived cells, providing a therapeutic approach tailored to individual patients. RNA-Seq data further enabled sample clustering by distinct gene expression profiles that corresponded to clinical parameters, conferring additional advantages over exome sequencing. The RNA-Seq-based diagnosis of NMDs achieves an increased diagnostic rate and provided pathogenic status information, which is not easily accessible through exome analysis.


View the world through a different lens: shadowing another provider.
The shadowing tool promotes understanding of other professions' roles in patient care.


[Effects of tobacco on antipsychotic treatments and their symptoms in schizophrenia].
The prevalence of cigarette smoking is significantly higher among patients with schizophrenia than in the general population. Several authors explained this excess of smoking by the self-medication hypothesis. It suggests that patients with schizophrenia smoke to reduce psychotic symptoms or antipsychotic side effects. In this study, we aimed to evaluate the prevalence of tobacco consumption in patients with schizophrenia and to test if smoking reduces psychotic and extra-pyramidal symptoms. We included 115 patients with schizophrenia (DSM IV) treated with conventional antipsychotics. We assessed psychotic symptoms with the Positive and Negative Syndrome Scale (PANSS) and extrapyramidal symptoms with the Simpson-Angus scale. Prevalence of smoking was 60% (80% in men and 22.5% in women). The majority of them started their consumption before their illness. Smokers and non-smokers had similar rates of psychotic and extrapyramidal symptoms with comparable doses of antipsychotics and anticholinergic agents which were prescribed for similar durations. In this study, patients with schizophrenia smoke a lot for reasons other than reducing psychotic or extrapyramidal symptoms.


[Cutaneous leishmaniasis in Algeria (author's transl)].
Report of 27 cases and comments on their epidemiological, clinical, immunological features and on the question of their treatment and prophylaxis.


Biosynthesis of phycobilins. Formation of the chromophore of phytochrome, phycocyanin and phycoerythrin.
Phycobiliproteins play important roles in photomorphogenesis and photosynthesis. The light-absorbing chromophores of the phycobiliproteins are linear tetrapyrroles (bilins) very similar in structure to the mammalian bile pigments. 5-Aminolaevulinate (5-ALA) is the first committed intermediate in phycobilin synthesis. The biosynthesis of 5-ALA, destined for phycobilins, occurs via the five-carbon pathway, now well established for tetrapyrrole synthesis in plants and distinct from the mammalian pathway. The phycobilins are formed by reduction of biliverdin which results from the synthesis and degradation of haem. This haem is an essential intermediate in the biosynthesis of phycobilins. Phycocyanobilin, the blue-green pigment found in certain algae and cyanobacteria, is formed from biliverdin via phytochromobilin, the chromophore of phytochrome. This leads to the likelihood that phytochromobilin is formed as an end product, or intermediate, in the synthesis of all phycobilins.


Tumor-suppressive microRNA-145 targets catenin δ-1 to regulate Wnt/β-catenin signaling in human colon cancer cells.
The constitutive activation of Wnt/β-catenin signaling plays a central role in colon cancer. MiR-145 was earlier identified as one of the microRNAs (miRNAs) down-regulated in colon cancer cells. However, the role of miR-145 in the Wnt/β-catenin signaling pathway is poorly understood. Here, we demonstrated that miR-145 played a pivotal role in the Wnt/β-catenin signaling pathway by perturbing the intracellular translocation of β-catenin in human colon cancer cells. The ectopic expression of miR-145 inhibited the growth of DLD-1 cells by disturbing β-catenin translocation into the nucleus, thereby leading to the down-regulation of LEF/TCF transcriptional target genes c-Myc and CyclinD1. We further demonstrated that miR-145 directly targeted catenin δ-1, contributing to the aberrant translocation of β-catenin through impaired nuclear shuttling with p21-activated kinase 4 (PAK4). These findings uncover a novel role of miR-145 in modulating intracellular translocation of β-catenin on Wnt/β-catenin signaling pathway.


Assessment of neutrophil chemotaxis and random migration in children and adults. Comparison between filter and agarose techniques.
Polymorphonuclear leucocyte migration was studied in 16 children and 11 normal adults, both by a filter technique and under agarose. Assays were carried out in parallel. There were no significant differences (p greater than 0.5) between adult controls and children's mean neutrophil migration coefficients within methods, but highly significant differences were found between methods (p less than 0.001) both in adult and children's samples. The observed intermethod differences are shown to be the result of increased random migration under agarose in both age groups.


Malignant fibrous histiocytoma of spermatic cord.
Malignant fibrous histiocytomas are very rare, particularly those related to urogenital organs. We report herein the third known case of this entity involving the spermatic cord. Summary of the previously reported 2 cases is given with recent follow-up. Prognosis is poor.


Cross-Sectional Study of Young Adults Diagnosed With Juvenile Fibromyalgia: Social Support and Its Impact on Functioning and Mood.
Juvenile-onset fibromyalgia (JFM) affects physical, social, and emotional functioning. Little is known about how social support and social interactions are impacted in the transition to young adulthood for patients diagnosed with JFM. Young adults (Mage = 21.6) diagnosed with JFM during adolescence (N = 94) and matched healthy controls (N = 33) completed measures of social network size and diversity, perceived social support, physical functioning, and depressive symptoms as part of a cross-sectional survey study. No difference in social network diversity was found, although JFM patients reported fewer total people within their social networks. JFM patients reported poorer emotional and tangible support and fewer positive social interactions than healthy controls. After controlling for condition and pain intensity, the level of perceived social support was a significant predictor of physical functioning and depressive symptoms, whereas social network size also contributed uniquely to physical functioning. Given the developmental importance of social support in adolescence and young adulthood, interventions should include methods of improving social support into fibromyalgia management.


RNAi-Based Functional Genomics in Hemiptera.
RNA interference (RNAi) is a powerful approach for sequence-specific gene silencing, displaying tremendous potential for functional genomics studies in hemipteran insects. Exploiting RNAi allows the biological roles of critical genes to be defined and aids the development of RNAi-based biopesticides. In this review, we provide context to the rapidly expanding field of RNAi-based functional genomics studies in hemipteran insects. We highlight the most widely used RNAi delivery strategies, including microinjection, oral ingestion and topical application. Additionally, we discuss the key variables affecting RNAi efficacy in hemipteran insects, including insect life-stage, gene selection, the presence of nucleases, and the role of core RNAi machinery. In conclusion, we summarise the application of RNAi in functional genomics studies in Hemiptera, focusing on genes involved in reproduction, behaviour, metabolism, immunity and chemical resistance across 33 species belonging to 14 families.


TIE-2/VEGF-R2 SAR and in vitro activity of C3-acyl dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole analogs.
Orally bioavailable, dual inhibitors of TIE-2/VEGF-R2 were identified by elaborating the C3/N13 SAR around a fused pyrrolodihydroindazolocarbazole scaffold. Analogs bearing a C3-thiophencarbonyl group were evaluated in enzymatic and cellular biochemical assays; two orally bioavailable analogs were further profiled in functional assays and found to inhibit microvessel growth in rat aortic explant cultures and inhibit Ang-1-stimulated chemotaxis of HUVECs.


Clinical utility of telomerase in cancer.
This review will focus on the clinical utilities of telomerase for human cancer diagnosis. Much attention has been focused on detection of telomerase activity and its essential components (hTR and hTERT) in cancer and noncancerous tissues. Expression of hTR and hTERT is upregulated in almost all human malignant tumors but not in benign or normal tissues with the exception of germline cells, proliferative stem cells, activated lymphocytes, and certain benign tumors. Thus, telomerase is a useful marker for cancer diagnosis and in some instance as a prognostic indicator of outcome. Telomerase detection in cells derived from breast fine needle aspirates, bronchial washes, and pancreatic juices show high sensitivity and specificity for cancer detection. In tissue samples, the level of telomerase activity is a useful prognostic indicator in certain adult cancers such as gastric and colon cancers and in neuroblastomas. Immunohistochemical detection of hTERT will facilitate exact diagnosis of the telomerase positive cells and expand the application of telomerase in cancer diagnosis.


Surfactant-free Synthesis of CuO with Controllable Morphologies and Enhanced Photocatalytic Property.
A green synthesis for nanoleave, nanosheet, spindle-like, rugby-like, dandelion-like and flower-like CuO nanostructures (from 2D to 3D) is successfully achieved through simply hydrothermal synthetic method without the assistance of surfactant. The morphology of CuO nanostructures can be easily tailored by adjusting the amount of ammonia and the source of copper. By designing a time varying experiment, it is verified that the flower- and dandelion-like CuO structures are synthesized by the self-assembly and Ostwald ripening mechanism. Structural and morphological evolutions are investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM) and UV-visible diffuse reflectance spectra. Additionally, the CuO nanostructures with different morphologies could serve as a potential photocatalyst on the photodecomposition of rhodamine B (RhB) aqueous solutions in the presence of H2O2 under visible light irradiation.


Mutanobactin A from the human oral pathogen Streptococcus mutans is a cross-kingdom regulator of the yeast-mycelium transition.
The recent investigation of a gene cluster encoding for a hybrid PKS-NRPS metabolite in the oral pathogen Streptococcus mutans UA159 yielded evidence that this natural product might play an important role regulating a range of stress tolerance factors. We have now characterized the major compound generated from this gene cluster, mutanobactin A, and demonstrated that this secondary metabolite is also capable of influencing the yeast-mycelium transition of Candida albicans.


Spatiotemporally resolved black carbon concentration, schoolchildren's exposure and dose in Barcelona.
At city level, personal monitoring is the best way to assess people's exposure. However, it is usually estimated from a few monitoring stations. Our aim was to determine the exposure to black carbon (BC) and BC dose for 45 schoolchildren with portable microaethalometers and to evaluate the relationship between personal monitoring and fixed stations at schools (indoor and outdoor) and in an urban background (UB) site. Personal BC concentra-tions were 20% higher than in fixed stations at schools. Linear mixed-effect models showed low R(2) between personal measurements and fixed stations at schools (R(2) ≤ 0.28), increasing to R(2) ≥ 0.70 if considering only periods when children were at schools. For the UB station, the respective R(2) were 0.18 and 0.45, indicating the importance of the distance to the monitoring station when assessing exposure. During the warm season, the fixed stations agreed better with personal measurements than during the cold one. Children spent 6% of their time on commuting but received 20% of their daily BC dose, due to co-occurrence with road traffic rush hours and the close proximity to the source. Children received 37% of their daily-integrated BC dose at school. Indoor environments (classroom and home) were responsible for the 56% BC dose.


Implementation of a peroral endoscopic myotomy program.
the aim of our study was to develop a peroral endoscopic myotomy (POEM) program in our Unit following a two-step sequence: training on animal models and supervision by an experienced endoscopist during the first human cases. a single endoscopist experienced in advanced endoscopy was trained in POEM. After observing POEM in referral centers, training was implemented on swine models (preclinical phase). Technical aspects and adverse events were prospectively recorded. A first subset of cases (group A) was compared to a second one (group B) to assess our progression. Finally, POEM was implemented in humans under the supervision of an experienced endoscopist (clinical phase). The outcomes and adverse events were prospectively recorded. during the preclinical phase, 15 POEM procedures were performed on live pigs. Severe adverse events (AE) were less frequent in group B than in group A (12 % vs 57 %, p = 0.07). After nine cases, a plateau of adverse events was reached. During the clinical phase, eleven POEM procedures were performed in patients under expert supervision. Technical and clinical (Eckardt score ≤ 3) success were 100 % and 91 %, respectively (follow-up 3-21 months). In two cases, intervention of an experienced endoscopist was required (cases 2 and 3) because of a difficult orientation at the esophagogastric junction. One mild pneumoperitoneum occurred, with no severe adverse events reported. training in animal models and supervision by an experienced endoscopist during the first cases could provide the necessary skills to perform POEM safely and effectively.


Impact of L-Arginine and L-Glutamine supplementation on growth performance and immune status in weanling pigs challenged with Escherichia coli F4.
Arginine (ARG) and Glutamine (GLN) have been reported to play significant roles in protein metabolism, immunity, and intestinal health in weanling pigs. The present study investigated the independent and interactive effect of supplementing ARG and GLN on pigs immune status and growth performance following an Escherichia coli F4 challenge. A total of 240 mixed-sex pigs (24 ± 2 d old; 7.3 ± 0.1 kg BW) were used in a 42-d experiment after selection for E. coli F4 susceptibility. The pigs were group-housed (3 pigs per pen), and pens were randomly assigned to five experimental treatments (N = 16 pens per treatment). Experimental treatments were: 1) a wheat-barley-soybean meal-based basal diet (CTRL), 2) a basal diet with 2500 mg/kg zinc oxide (ZnO), 3) a basal diet + 0.5% Glutamine (0.5% GLN), 4) basal diet + 0.5% Arginine (0.5% ARG), and 5) basal diet with 0.5% Glutamine + 0.5% Arginine (0.5% GLN + ARG). All Pigs were inoculated with E. coli F4 on days 7, 8, and 9 post-weaning. Rectal swabs were taken from each pig and plated on blood agar plates for E. coli F4 presence. Blood and fecal samples were taken to determine the acute phase response and selected fecal biomarkers for the immune response. Growth performance and fecal scores were recorded. Fecal swabs resulted in no positive pig for E. coli F4 before inoculation and 73.3% positive postinoculation. Diarrhea incidence during days 7 to 14 was significantly lower for the ZnO treatment (P < 0.05). The haptoglobin level on day 3 was lower than days 10 and 20, irrespective of treatment (P < 0.05). The albumin level was lower on day 20 compared to days 3 and 10 (P < 0.05). There was no treatment effect on albumin levels regardless of sampling day (P > 0.05). The PigMAP was lowest on day 3 and highest on day 10 (P < 0.05). We did not observe significant treatment differences (P > 0.05) in myeloperoxidase and calprotectin. Pancreatitis-associated protein was higher in the ZnO (P = 0.001) treatment than in the other treatments. Fecal IgA tended (P = 0.10) to be higher in the ZnO and 0.5% ARG treatments. There were no performance differences, except during days 0 to 7, where the ZnO treatment was lower in average daily gain and average daily feed intake (P < 0.001), while feed efficiency (G:F) FE was similar across treatments. In summary, no improved performance was observed with either ARG, glutamate, or both. The immune response results showed that the E. coli F4 challenge may have exacerbated the acute phase response; hence, the benefits of dietary treatments did not go beyond immune repair and reduction in inflammation.


Mitochondrial DNA Variations in Colombian Creole Sheep Confirm an Iberian Origin and Shed Light on the Dynamics of Introduction Events of African Genotypes.
The genetic origins and diversity of Creole sheep from five regions of Colombia were investigated based on mitochondrial DNA (mtDNA) variations across 89 sequences from five breeds: one wool Creole sheep (CL) and four hair Creole sheep, including Ethiopian (OPCE), Sudan (OPCS), Pelibuey (OPCP) and Wayúu (OPCW). A global comparison was done using 62 haplotypes from Iberian, African, Indian, Caribbean, Mexican, Caucasian and European sheep based on sequences retrieved from GenBank. This study aimed to identify the maternal origin of Colombian Creole sheep and their genetic relationships at a global level. The results showed 31 different haplotypes from Colombian Creole sheep, which can be assigned to maternal lineage B, the most common lineage found in European sheep breeds and the only one found in several Iberian breed (e.g., Churra, Spanish Merino) that most likely participated in the Creole formation. Additional analyses showed that wool and hair sheep retained a broad genetic identity despite being geographically separated. The global-level phylogenetic analysis revealed that Colombian Creole sheep belong to a distinct and defined genetic lineage that is likely the result of a founder effect with ecotypes of Iberian descent and the subsequent introduction of foreign breeds. This is consistent with historical reports on the presence of sheep in South America and, particularly, Colombia.


Acute effect of sildenafil on central hemodynamics in mechanically ventilated patients with WHO group III pulmonary hypertension and right ventricular failure necessitating administration of dobutamine.
Sildenafil decreases pulmonary vascular resistance index (PVRI), in patients with pulmonary hypertension (PH). We investigated sildenafil's effects on central hemodynamics of mechanically ventilated patients with WHO group-III PH and RV failure necessitating dobutamine administration. Prospective non-controlled study involving 12 (9 males, 59 ± 4 years old), patients with the above characteristics. All patients in phase-1 (days 1-2) received dobutamine (5 μg/kg/min IV). During phase-2 (days 3-6), sildenafil was started via nasogastric tube (80 mg/day) and dobutamine discontinuation was attempted. Patients were designated responders or non-responders based on whether dobutamine could be stopped or not. Phase-3 lasted from day 7 to day of weaning from mechanical ventilation; or if weaning failed, until day 20 following admission (end-of-study). Invasive and echocardiographic parameters were repeatedly recorded throughout the study. Significantly changed parameters (P<0.025) from baseline to phase-1, -2 and -3 (%change of mean ratios), in responders (n=7) included among others PVRI (-40%, -51%, -42%), RV stroke work index (RVSWI: 43%, 79%, 41%) and cardiac index (49%, 54%, 48%), which also differed significantly from non-responders (N=5). In phases-1 and -3 non-responders had not significant changes, in phase-2 PVRI (27%) and RVSWI (-22%) changed significantly. In contrast to non-responders, all responders were weaned from mechanical ventilation until the end-of-study (P<0.025). Sildenafil may improve central hemodynamics and RV function indices in ventilated patients with WHO group-III PH and RV failure requiring dobutamine infusion, when they respond favorably to the latter. Accordingly, an adequate RV systolic reserve may be mandatory for sildenafil to exert its actions.


The Major Histocompatibility Complex Class III Haplotype Ltab-Ncr3 Regulates Adjuvant-Induced but Not Antigen-Induced Autoimmunity.
Rheumatoid arthritis is a complex disease associated with >100 risk loci, with the strongest association from the major histocompatibility complex (MHC) region. Here, we analyzed a new genetic association in the MHC class-III region (MHC-III) using adjuvant- and antigen-induced arthritis models. In addition, we used models for multiple sclerosis for comparison and dissected the MHC-III-mediated mechanisms of importance for antibody and T-cell responses to antigens. With the use of a panel of MHC-III recombinant inbred strains, we found that the 33-kb Ltab-Ncr3 haplotype in MHC-III was linked to the induction of arthritis with incomplete Freund's adjuvant, with similar effects in arthritis induced by several oil adjuvants (hexadecane, heptadecane, squalene, arlacel). Adoptive T-cell transfer experiment showed that this arthritis-protective effect operated during the priming of T cells by controlling their arthritogenicity. Interestingly, Ltab-Ncr3 did not regulate autoimmune diseases induced with tissue-specific antigens emulsified in adjuvant oils, such as collagen-induced arthritis or experimental autoimmune encephalomyelitis. No effect on antibody or T-cell response to tissue antigens in the Ltab-Ncr3 could be demonstrated. The finding that Ltab-Ncr3 is specific in regulating adjuvant-induced arthritis but not antigen-induced autoimmunity, and with unique effects on priming of autoreactive and arthritogenic T cells, provides new insight for understanding the regulation of autoimmune diseases.


Biochemical mechanisms of cephaloridine nephrotoxicity.
Large doses of the cephalosporin antibiotic, cephaloridine, produce acute proximal tubular necrosis in humans and in laboratory animals. Cephaloridine is actively transported into the proximal tubular cell by an organic anion transport system while transport across the lumenal membrane into tubular fluid appears restricted. High intracellular concentrations of cephaloridine are attained in the proximal tubular cell which are critical to the development of nephrotoxicity. There is substantial evidence indicating that oxidative stress plays a major role in cephaloridine nephrotoxicity. Cephaloridine depletes reduced glutathione, increases oxidized glutathione and induces lipid peroxidation in renal cortical tissue. The molecular mechanisms mediating cephaloridine-induced oxidative stress are not well understood. Inhibition in gluconeogenesis is a relatively early biochemical effect of cephaloridine and is independent of lipid peroxidation. Furthermore, cephaloridine inhibits gluconeogenesis in both target (kidney) and non-target (liver) organs of cephaloridine toxicity. Since glucose is not a major fuel of proximal tubular cells, it is unlikely that cephaloridine-induced tubular necrosis is mediated by the effects of this drug on glucose synthesis.


Male-killing Wolbachia do not protect Drosophila bifasciata against viral infection.
Insect symbionts employ multiple strategies to enhance their spread through populations, and some play a dual role as both a mutualist and a reproductive manipulator. It has recently been found that this is the case for some strains of Wolbachia, which both cause cytoplasmic incompatibility and protect their hosts against viruses. Here, we carry out the first test as to whether a male-killing strain of Wolbachia also provides a direct benefit to its host by providing antiviral protection to its host Drosophila bifasciata. We infected flies with two positive sense RNA viruses known to replicate in a range of Drosophila species (Drosophila C virus and Flock House virus) and measure the rate of death in Wolbachia positive and negative host lines with the same genetic background. Both viruses caused considerable mortality to D. bifasciata flies, with Drosophila C virus killing 43% more flies than the uninfected controls and Flock House virus killing 78% more flies than the uninfected controls. However, viral induced mortality was unaffected by the presence of Wolbachia. In the first male-killing Wolbachia strain tested for antiviral effects, we found no evidence that it conferred protection against two RNA viruses. We show that although antiviral resistance is widespread across the Wolbachia phylogeny, the trait seems to have been lost or gained along some lineages. We discuss the potential mechanisms of this, and can seemingly discount protection against these viruses as a reason why this symbiont has spread through Drosophila populations.


Platelet sensitivity in vitro to adenosine-5'-diphosphate and prostacyclin and diabetic retinopathy.
Platelet sensitivity to adenosine diphosphate and prostacyclin in diabetes has been assessed using collision theory and the concept of 'sticking probability' (the probability of particle union). Twenty Type 1 (insulin-dependent) diabetic men (10 with no or minimal retinopathy and a matched group of 10 with proliferative retinopathy) and 10 age-matched nondiabetic men were studied. Platelets from the 20 diabetic patients required, on average, 37% less adenosine diphosphate to achieve a sticking probability of 0.5 (ED50) compared with platelets from the non-diabetic subjects (medians 1.50 and 0.95 mumol/l, respectively; p less than 0.01). The platelet prostacyclin response was assessed by the dissociation constant (Ki) for inhibition of adenosine diphosphate-induced aggregation. Platelets from the diabetic patients had similar prostacyclin sensitivity to those from the non-diabetic subjects (medians 0.42 and 0.42 respectively). Diabetic patients with and without retinopathy had similar platelet sensitivity to both adenosine diphosphate and prostacyclin.


[Implementing Recovery-Orientation in Psychoeducation - An Attempt].
This article explores the diverging implementation of the main principles of recovery in two group settings similar to psychoeducation. Both groups were qualitatively examined, using participant observation, and compared to each other afterwards. Both groups used various models of disease, whereby the participants' subjective experiences were favoured. Kinds of interaction and communication among participants were dependent on spatial characteristics of both group settings. Various types of knowledge were employed, structuring the relations among participants. More standardized modes of transferring knowledge, often utilized in psychoducational settings, are less compatible with such an approach.


Ventilatory Effects of Acute Intermittent Hypoxia in Conscious Dystrophic Mice.
Exposure to acute intermittent hypoxia (AIH) elicits a form of respiratory plasticity known as long-term facilitation (LTF). Interest has grown in developing AIH interventions to treat ventilatory insufficiency, with promising results in spinal cord injury and amyotrophic lateral sclerosis. Therapeutic AIH may have application in neuromuscular disorders including muscular dystrophies. We sought to establish hypoxic ventilatory responsiveness and the expression of ventilatory LTF in X-linked muscular dystrophy (mdx) mice.Experiments were performed in 15 male wild-type (BL10) and 15 male mdx mice at 4 months of age. Ventilation was assessed using whole-body plethysmography. Baseline measures of ventilation and metabolism were established. Mice were exposed to 10 successive bouts of hypoxia, each lasting 5 min, interspersed with 5-min bouts of normoxia. Measurements were taken for 60 min following termination of AIH.In mdx mice, ventilation was significantly increased 60 min post-AIH compared to baseline. However, metabolic CO2 production was also increased. Therefore, ventilatory equivalent was unaffected by AIH exposure, i.e., no ventilatory LTF manifestation. In wild-type mice, ventilation and metabolism were not affected by AIH.Eliciting ventilatory LTF is dependent on many factors and may require concomitant isocapnia or hypercapnia during AIH exposures and/or repeated daily AIH exposures, which is worthy of further pursuit.


Adjuvant chemotherapy with vinblastine and bleomycin in stage B nonseminomatous germ cell tumors of the testis.
Between 1974 and 1980, 48 lymph node dissections were done for nonseminomatous tumors. Of 23 patients with pathologic stage A disease 1 (4 per cent) suffered recurrence but is free of disease after chemotherapy and pulmonary resection. All 23 patients (100 per cent) are free of disease. Adjuvant chemotherapy with high dose vinblastine and constant infusion of bleomycin was given in 25 patients with stage stage B disease and none had maintenance chemotherapy. Of these 25 patients 2 (8 per cent) had evidence of recurrent disease after adjuvant chemotherapy and both are free of disease after further chemotherapy, which included cis-platinum. One patient died after a second primary embryonal carcinoma developed in the remaining testis 3 years after the initial tumor. Twenty-four of the 25 patients with stage B tumor (96 per cent) are free of disease 15 months to greater than 7 years after therapy.


Inborn errors of metabolism: psychosocial challenges and proposed family systems model of intervention.
Inborn errors of metabolism result in psychosocial crises that challenge individual and familial modes of functioning across the life cycle. Increased stress, mood disorders, interpersonal challenges, decreased quality of life, and grief reactions are all common for patients and their families. To effectively care for these patients, a holistic approach to their care, which incorporates their social context, is essential. Patients and their families need support as they focus on immediate practical demands, grieve over illness-related losses, and reorient future expectations. A family systems based model provides a flexible and individualized approach to care that allows for optimal psychosocial adjustment throughout the disease process.


Induction of autogamy by transfer of macronuclear karyoplasm in Paramecium tetraurelia.
Macronuclear karyoplasm was transplanted from pre-autogamous donor cells (clonal age, 22 fissions) into the macronucleus of young recipient cells (2 fissions after autogamy occurred) by means of microinjection. A reciprocal experiment was carried out by injecting karyoplasm from young clonal age donors into pre-autogamous recipients. In the case of karyoplasm transfer from pre-autogamous donors to young recipients, autogamy occurred early in 67% of injected cells, whereas reciprocal injections had no influence on the onset of autogamy, and all of the injected cells underwent autogamy. Such results indicate a distinct role of pre-autogamous cells of macronucleus in the induction of autogamy.


Cutaneous T-cell lymphoma.
Cutaneous T-cell lymphoma comprises a heterogeneous group of lymphoproliferative disorders characterized by clonal expansions of mature, post-thymic T cells that infiltrate the skin. This article discusses the staging, prognosis, and treatment of mycosis fungoides and Sézary syndrome.


Efficacy, acceptability and safety of cognitive behavioural therapies in fibromyalgia syndrome - A systematic review and meta-analysis of randomized controlled trials.
This updated systematic review aimed at evaluating the efficacy, acceptability and safety of cognitive behavioural therapies (CBTs) in fibromyalgia syndrome (FMS). Clinicaltrials.gov, Cochrane Library, MEDLINE, PsycINFO and SCOPUS were searched from September 2013 to May 2017. Randomized controlled trials (RCTs) comparing CBTs with controls were analysed. Primary outcomes were ≥50% pain relief, ≥20% improvement of health-related quality of life (HRQoL), negative mood, fatigue, disability, acceptability and safety at end of therapy and at 6 months follow-up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI). 29 RCTs with 2509 subjects were included. CBTs were superior to controls (waiting list, attention control, treatment as usual, other active non-pharmacological therapies) in pain relief of 50% or greater (RD 0.05 [95% CI 0.02-0.07] (high-quality evidence), improvement of HRQoL of 20% or greater (RD 0.13 [95% CI 0.00-0.26], (moderate quality evidence), and in reducing negative mood (SMD -0.43 [95% CI -0.62 to -0.24]) (high-quality evidence), disability (SMD -0.30 [95% CI -0.52 to -0.08]) (high-quality evidence) and fatigue (SMD - 0-27 [95% CI -0.50 to -0.03]) (high-quality evidence). There were no statistically significant differences between CBTs and controls in acceptability and safety (high-quality evidence). The update did not change the major findings of the previous review. CBTs provided a clinically relevant benefit over control interventions in reducing some key symptoms of FMS and disability at the end of treatment. This updated systematic review with meta-analysis on cognitive behavioural therapies (CBTs) including acceptance-based CBTs endorse the efficacy and tolerability of CBTs in reducing key symptoms and disability in FMS in the short- and long-term if compared to waiting list, treatment as usual, attention controls and active non-pharmacological therapies. CBTs did not differ in efficacy except superiority for coping with pain and tolerability from recommended drug therapy (pregabalin and/or duloxetine).


Multi-liposomal containers.
Small unilamellar liposomes, 40-60 nm in diameter, composed of anionic diphosphatidylglycerol (cardiolipin, CL(2-)) or phosphatidylcerine (PS(1-)) and zwitter-ionic egg yolk lecithin (EL) or dipalmitoylphosphatidylcholine (DPPC), electrostatically complex with polystyrene microspheres, ca. 100 nm in diameter, grafted by polycationic chains ("spherical polycationic brushes", SPBs). Polymer/liposome binding studies were carried out using electrophoretic mobility (EPM), dynamic light scattering (DLS), fluorescence, conductometry, differential scanning calorimetry (DSC), and cryogenic transmission electron microscopy (cryo-TEM) as the main analytical tools. By these means a remarkably detailed picture emerges of molecular events inside a membrane. The following are among the most important conclusions that arose from the experiments: (a) binding of liposomes to SPBs is accompanied by flip-flop of anionic lipids from the inner to the outer leaflet of the liposomal membrane along with lateral lipid segregation into "islands". (b) The SPB-induced structural reorganization of the liposomal membrane, together with the geometry of anionic lipid molecules, determines the maximum molar fraction of anionic lipid (a key parameter designated as ν) that ensures the structural integrity of liposomes upon complexation: ν=0.3 for liposomes with conically-shaped CL(2-) and ν=0.5 for liposomes with anionic cylindrically-shaped PS(1-). (c) The number of intact liposomes per SPB particle varies from 40 for (ν=0.1) to 13 (ν=0.5). (d) By using a mixture of liposomes with variety of encapsulated substances, multi-liposomal complexes can be prepared with a high loading capacity and a controlled ratio of the contents. (e) In order to make the mixed anionic liposomes pH-sensitive, they are additionally modified by 30 mol% of a morpholinocyclohexanol-based lipid that undergoes a conformational flip when changing pH. Being complexed with SPBs, such liposomes rapidly release their contents when the pH is reduced from 7.0 to 5.0. The results allow loaded liposomes to be concentrated within a rather small volume and, thereby, the preparation of multi-liposomal containers of promise in the drug delivery field.


Non-random effect on RNA synthesis in liver chromatin by administration of dimethylnitrosamine to mice.
The effect of dimethylnitrosamine on functional activities of liver chromatin was studied in mice. After a single dose of dimethylnitrosamine injected i.v. (25 mg/kg body wt, 45 min before sacrifice) liver nuclei were isolated and incubated with micrococcal nuclease (EC 184.108.40.206) to an acid-solubility of 2.5% of total DNA. Chromatin was fractionated into a 1,200 g pellet P1, 102,000 g pellet P2 and supernatant fraction S2. Chromatin-bound RNA polymerase I plus III activity decreased 15% in the P1 and 25% in the P2 fraction. No changes in activity were observed in the S2 fraction. Chromatin-bound RNA polymerase II activity decreased 19% in the P1, 49% in the P2 and 32% in the S2 fraction. Heparin stimulated RNA polymerase II activity decreased 10% in the P1 and 44% in the P2 fraction. Formation of initiation in nuclear lysates with RNA polymerase from Escherichia coli increased after administration of dimethylnitrosamine suggesting an increase in the number of sites available for the start of new RNA chains. The results show that limited digestion of nuclei with endonuclease cleaves chromatin regions which are more affected by dimethylnitrosamine than the total chromatin suggesting a non-random effect of the hepatotoxin on chromatin. Modifications of the DNA template by dimethylnitrosamine is indicated by the change in number of initiation complexes.


Maternal versus fetal inflammation and respiratory distress syndrome: a 10-year hospital cohort study.
To determine the impact of maternal and fetal intrauterine inflammatory responses (chorioamnionitis and umbilical vasculitis) on the development of neonatal respiratory distress syndrome (RDS) in preterm infants. The study included all infants <30 weeks' gestation born at the Royal Prince Alfred Hospital, Sydney, Australia, and admitted to neonatal intensive care from 1992 to 2001. Those without placental examination were excluded. Antenatal and perinatal data were extracted from prospectively kept hospital databases and correlated with the independent, central neonatal database. Placentae were examined prospectively using a standardised, semi-quantitative method. A diagnosis of neonatal RDS. There were 766 eligible babies and 724 (94.5%) had placental examination. The mean (SD) gestational age of the cohort was 27.1 (1.6) weeks. Antenatal maternal steroids were given to 93.6%. Histological chorioamnionitis alone was evident in 19.1% of infants, and chorioamnionitis with umbilical vasculitis in 30.2%. Regression analysis showed that increasing gestational age (adjusted odds ratio (OR) 0.72, 95% CI 0.64 to 0.81), chorioamnionitis (adjusted OR 0.49, 95% CI 0.31 to 0.78), and chorioamnionitis with umbilical vasculitis (adjusted OR 0.23, 95% CI 0.15 to 0.35) were associated with a significant reduction in RDS. Factors associated with increased odds of RDS were multiple gestation (twin or triplet pregnancies), pregnancy-induced hypertension and an Apgar score <4 at 1 minute. Maternal and fetal intrauterine inflammatory responses are both protective for RDS. The presence of chorioamnionitis with umbilical vasculitis is associated with a markedly greater reduction of RDS than chorioamnionitis alone.


Lessons learned for pandemic preparedness: A collaborative network is imperative.
The scientific community improvised to respond quickly to the SARS-CoV-2 pandemic without a template on how to work together on a global scale to understand and combat the virus. Here, we describe how we tackled impediments to success and the valuable lessons learned that prepare us for a future pandemic.


Bilateral muscle atrophy after anterior cruciate ligament reconstruction in rats: Protective effects of anti-inflammatory drug celecoxib.
Muscle atrophy after anterior cruciate ligament (ACL) reconstruction occurs bilaterally and contributes to a decrease in muscle strength. However, effective treatment strategies for ACL reconstruction-induced muscle atrophy have not been established. We examined the effects of anti-inflammatory drug on muscle atrophy after ACL reconstruction. Rats were divided into groups according to treatment received: untreated control (n = 4), arthrotomy (n = 6), ACL transection (n = 7), ACL reconstruction (n = 8), and ACL reconstruction plus anti-inflammatory drug celecoxib (CBX; 50 mg/kg/day) administration (n = 8). At one-week post-surgery, the muscle fiber cross-sectional area (CSA) in the rectus femoris (RF) and semitendinosus (ST) was measured to assess muscle atrophy. In addition, we examined joint swelling and serum C‑reactive protein (CRP) levels to assess local and systemic inflammation, respectively. Each additional procedure (i.e., arthrotomy, ACL transection, and ACL reconstruction) gradually decreased the muscle fiber CSAs in the RF and ST on both operated and contralateral sides. The degree of muscle fiber atrophy on the operated side was larger than that detected on the contralateral side. Moreover, ACL reconstruction induced joint swelling on the operated side and tended to increase serum CRP levels. CBX lessened the RF atrophy on both sides and was associated with less joint swelling and a smaller increase CRP level; however, it did not affect ST atrophy on either side. Anti-inflammatory treatments after ACL reconstruction may be effective in lessening muscle atrophy in the quadriceps, but not in the hamstrings.


[Investigations concerning the hypothalamic-hypophysial regulation of aldosterone secretion (author's transl)].
In 17 patients with retrospectively healthy adrenals we performed a LHRH-test, a TRF-test and an ACTH-test in the short modification. Additionally we determined plasma aldosterone and renine levels. Concerning the LHRH-tests and the TRF-tests we did not find any differences on the aldosterone values. Concerning the ACTH-tests in the short modification we found an increase of the aldosterone values which resembled that of the cortisol levels (increase of cortisol 104.7%, increase of aldosterone 93.3%). The renin values remained unchanged. Therefore the plasma aldosterone levels are modified in accordance with the cortisol levels by hypophysial influences.


With or Without Residual C-Peptide, Patients with Type 2 Diabetes Realize Glycemic Benefits from Real-Time Continuous Glucose Monitoring.
Real-time continuous glucose monitoring (RT-CGM) is superior to blood glucose monitoring (BGM) for adults with insulin-treated type 2 diabetes (T2D); however, the utility of C-peptide levels for predicting the magnitude of the glycemic benefits is controversial. Data were from a subset of 147 participants in the MOBILE study who were treated with basal-only insulin and who had baseline C-peptide levels ≥0.5 ng/mL. Participants were randomized to treatment with either RT-CGM (n = 100) or BGM (n = 47). Between-group differences in hemoglobin A1c (HbA1c) and time in range (TIR) changes were assessed. The between-group difference in HbA1c favored the RT-CGM group (by 0.58 percentage points, P = 0.004 at 3 months and by 0.42 percentage points, P = 0.04 at 8 months). TIR was 16% higher, and time >180 mg/dL was 16% lower, in the RT-CGM group at 8 months (P = 0.002 for each). In T2D managed with basal insulin, RT-CGM benefits occur for those with residual insulin secretory capacity. Clinical Trial Identifier: NCT03566693.


Real-time functional magnetic resonance imaging neurofeedback training of amygdala upregulation increases affective flexibility in depression.
Decreased affective flexibility is associated with depression symptoms, and it has been suggested that common interventions may target this mechanism. To explore this hypothesis, we evaluated whether real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training to increase the amygdala responses during positive memory recall resulted in both symptom improvements, as has been observed previously, and flexibility to decrease amygdala reactivity in response to a cognitive task among patients with major depressive disorder (MDD). In a double-blind, placebo-controlled, randomized clinical trial, adults with MDD received 2 sessions of rtfMRI-nf training to increase their amygdala (experimental group) or parietal (control group) responses during positive autobiographical memory recall. We evaluated signal changes in the amygdala during both the positive memory neurofeedback and a subsequent counting condition. We included 38 adults with MDD, including 16 in the experimental group and 22 in the control group. In the experimental group, amygdala activity increased (t > 2.01, df < 27, p < 0.05, d > 0.5) and depressive symptoms decreased (-8.57, 95 % confidence interval [CI] -15.12 to -2.59; t 13 = -3.06, p = 0.009, d = 1). Amygdala activity during the count condition decreased after rtfMRI-nf (-0.16, 95 % CI -0.23 to -0.09; t 396 = 4.73, p < 0.001, d = 0.48) and was correlated with decreased depression scores (r = 0.46, p = 0.01). We replicated previous results and extended them to show decreased amygdala reactivity to a cognitive task during which no neurofeedback was provided. The count condition was reported by participants as negative, but emotionality or accuracy during this condition was not assessed. These results suggest that nominally targeting unidimensional change in neural mechanisms could have implications for bidirectional control, increasing the likely reach and explanatory framework for how common depression interventions work.Trial registration: ClinicalTrials.gov NCT02709161.


Effect of surface treatments on the bond strength of soft denture lining materials to an acrylic resin denture base.
Adhesive failure between acrylic resin and resilient liner material is commonly encountered in clinical practice. The purpose of this study was to evaluate the effect of different surface treatments on the bond strength of 2 different resilient lining materials to an acrylic resin denture base. Ninety-six dumbbell-shaped specimens were fabricated from heat-polymerized acrylic resin, and 3 mm of the material was cut from the thin midsection. The specimens were divided into 6 groups according to their surface treatments: no surface treatment (control group), 36% phosphoric acid etching (acid group), erbium:yttrium-aluminum-garnet (Er:YAG) laser (laser group), airborne-particle abrasion with 50-μm Al2O3 particles (abrasion group), an acid+laser group, and an abrasion+laser group. The specimens in each group were divided into 2 subgroups according to the resilient lining material used: heat-polymerized silicone based resilient liner (Molloplast B) and autopolymerized silicone-based resilient liner (Ufi Gel P). After all of the specimens had been polymerized, they were stored in distilled water at 37°C for 1 week. A tensile bond strength test was then performed. Data were analyzed with a 2-way ANOVA, and the Sidak multiple comparison test was used to identify significant differences (α=.05). The effects of the surface treatments and resilient lining materials on the surface of the denture base resin were examined with scanning electron microscopy. The tensile bond strength was significantly different between Molloplast B and Ufi Gel P (P<.001). The specimens of the acid group had the highest tensile bond strength, whereas those of the abrasion group had the lowest tensile bond strength. The scanning electron microscopy observations showed that the application of surface treatments modified the surface of the denture base resin. Molloplast B exhibited significantly higher bond strength than Ufi Gel P. Altering the surface of the acrylic resin denture base with 36% phosphoric acid etching increased bond strength.


Studies on the parasitic helmiths of Korea: I. Trematodes of rodents.
A total of 624 rodent of six species was examined for trematodes. Five species of trematodes were considered, of which Fibricola seoulensis sp. nov. was reported as a new species. Plagiorchis muris, Echinostoma cinetorchis and Euparyphium murinum was recorded for the first time from Korea. Descriptions are included for each species considered.


Restrictions to Pharmacy Ownership and Vertical Integration in Estonia-Perception of Different Stakeholders.
From 2020, the ownership of community pharmacies in Estonia will be limited to the pharmacy profession, and the vertical integration of wholesale companies and community pharmacies will not be allowed. The aim of this study was to evaluate the perception of different stakeholders in primary healthcare toward the new regulations of the community pharmacy sector in Estonia. A qualitative electronic survey was distributed to the main stakeholders in primary healthcare and higher education institutions providing pharmacy education (n = 40) in May 2015. For data analysis, the systematic text condensation method was used. The study participants described two opposing positions regarding the development of community pharmacies in the future. Reform supporters emphasized increased professional independence and more healthcare-oriented operation of community pharmacies. Reform opponents argued against these ideas as community pharmacists do not have sufficient practical experience and finances to ensure sustainable development of the community pharmacy sector in Estonia. Based on the current perception of all respondents, the future operation of the community pharmacy sector in Estonia is unclear and there is urgent need for implementation criteria for the new regulations.


Rhizocticin A, an antifungal phosphono-oligopeptide of Bacillus subtilis ATCC 6633: biological properties.
Rhizocticin A, the main component of the antifungal, hydrophilic phosphono-oligopeptides of Bacillus subtilis ATCC 6633, was used for sensitivity testing and experiments into the molecular mechanism of the antibiotic action. Budding and filamentous fungi as well as the cultivated nematode Caenorhabditis elegans were found to be sensitive, whereas bacteria and the protozoon Paramecium caudatum were insensitive. Rhizoctonia solani was inhibited in agar dilution tests but not in diffusion tests. The antifungal effect of rhizocticin A was neutralized by a variety of amino acids and oligopeptides. Oligopeptide influence was mainly understood as transport antagonism, and it was concluded that the antibiotic enters the recipient cell via the peptide transport system. L- and D-cystine were also identified as potent, general antagonists of the oligopeptide transport. The rhizocticin-antagonism of four other amino acids was taken as a clue to the site of action. Provided that rhizocticin A is split by peptidases of the target cell into inactive L-arginine and toxic L-2-amino-5-phosphono-3-cis-pentenoic acid (L-APPA), the latter may interfere with the threonine or threonine-related metabolism.


Aspirin and the prevention of colorectal cancer.
A large body of evidence from basic science, epidemiologic observations and population-based studies demonstrates that aspirin, as well as other non-steroidal anti-inflammatory drugs, has a chemopreventive effect on several cancer types and, more specifically, in CRC. This protective effect includes prevention of adenoma recurrence and reduction of CRC incidence and mortality. Although the protective effect appears to depend on the dose and the drug, the most important factor is the duration of exposure. However, the lowest effective dose, treatment duration, specific target populations, and effects on survival have not been defined yet. More important, data on the risk-benefit profile for cancer prevention are insufficient and, accordingly, no definitive recommendation can be made at present. In this article, besides reviewing current knowledge of the mechanisms involved in aspirin-based CRC chemoprevention, we will be focused on randomized controlled studies assessing its efficacy in high-, moderate- and average-risk populations.


Computational phosphorylation network reconstruction: methods and resources.
The succession of protein activation and deactivation mediated by phosphorylation and dephosphorylation events constitutes a key mechanism of molecular information transfer in cellular systems. To deduce the details of those molecular information cascades and networks has been a central goal pursued by both experimental and computational approaches. Many computational network reconstruction methods employing an array of different statistical learning methods have been developed to infer phosphorylation networks based on different types of molecular data sets such as protein sequence, protein structure, or phosphoproteomics data. In this chapter, different computational network inference methods and resources for biological network reconstruction with a particular focus on phosphorylation networks are surveyed.


Decompressive Craniectomy in Spontaneous Intracerebral Hemorrhage: A Comparison with Standard Craniotomy Using Propensity-Matched Analysis.
Spontaneous intracerebral hemorrhage carries a poor prognosis with a 30-day mortality rate of 35%-52%. There is no standardized surgical technique for treatment of spontaneous intracerebral hemorrhage. While minimally invasive techniques are popular, there has been renewed interest in decompressive craniectomy (DC). We compared surgical and functional outcomes of standard craniotomy and DC, both with hematoma evacuation, in the surgical treatment of supratentorial spontaneous intracerebral hemorrhage. This 4-year retrospective study compared outcomes of 2 surgical techniques: standard craniotomy in group A (n = 78) and DC in group B (n = 54). To minimize bias in case selection, propensity matching was performed to match preoperative Glasgow Coma Scale score and hematoma volume (group C). Hematoma evacuation was performed in 132 patients. Mean age of patients was 53.3 years, 50.5 years, and 52.06 years in groups A, B, and C, respectively. Median preoperative Glasgow Coma Scale score was 9, 7, and 8 (P = 0.01; P = 0.45), and mean hematoma volume was 46.21 mL, 50.91 mL, and 49.90 mL. Overall mortality was 26.5%; 62.9% (n = 22) of deaths were in group A, and 37.1% (n = 13) were in group B (P = 0.69). Median modified Rankin Scale score was similar in both groups, both at discharge and at 3 months. After determining propensity scores, mortality and outcomes of matched groups remained similar. DC with hematoma evacuation does not appear to provide a significant advantage over standard craniotomy with regard to functional outcomes and mortality. DC may overcome the need for subsequent surgery in accommodating postoperative mass effect in residual bleeds and rebleeds but is associated with greater blood loss and longer operative duration.


Comparison of Clinical Efficacies of Preoperatively Initiated Naproxen Sodium-Codeine Phosphate in Combination, Diclofenac Potassium, and Benzydamine Hydrochloride for Pain, Edema, and Trismus After Extraction of Impacted Lower Third Molar: A Randomized Double-Blind Study.
The aim of this study was to compare the clinical efficacies of naproxen sodium-codeine phosphate in combination, benzydamine hydrochloride, and diclofenac potassium for pain, edema, and trismus after lower third molar extraction. Ninety healthy volunteers in whom impacted third molar extraction was indicated were randomly distributed into 3 groups. One hour before the tooth-extraction process, patients were administered one of the following drugs: naproxen sodium, 550 mg, and codeine phosphate, 30 mg, in a tablet; diclofenac potassium, 50 mg, in a coated pill; or benzydamine hydrochloride, 50 mg, in a coated pill. Pain assessment was conducted via a visual analog scale; edema assessment, by measuring the distances between predetermined facial landmarks; and trismus assessment, by measuring interincisal distance. Regarding rescue analgesics (paracetamol, 500 mg), the number and time of use by patients were recorded. Naproxen sodium-codeine phosphate was more effective for pain, edema, and trismus than diclofenac potassium and benzydamine hydrochloride (P < .05). Benzydamine hydrochloride yielded similar clinical responses to diclofenac potassium (P > .05). No drug-related side effects were observed. Naproxen sodium-codeine phosphate constitutes the drug of choice after the extraction of a patient's impacted lower third molar. Benzydamine hydrochloride has similar efficacy to diclofenac potassium, and it can be used as a nonsteroidal anti-inflammatory analgesic drug.


Position affects distribution of ventilation in the lungs of older people: an experimental study.
What is the effect of sitting and side-lying on the distribution of ventilation during tidal breathing in healthy older people? Randomised, within-participant, experimental study. Ten healthy people more than 65 years old. Tidal breathing during sitting and right side-lying. Distribution of ventilation as a percentage of total counts using Technetium-99m Technegas lung ventilation imaging. In sitting, the ratio of the distribution of ventilation to apical: middle: basal regions was 1: 3.5: 3.3 in the right lung, and 1: 2.9: 2.3 in the left lung. In right side-lying, 32% (95% CI 22 to 43) more ventilation was distributed to the right lung than to the left lung. The ratio of the distribution of ventilation to apical: middle: basal regions was 1: 2.8: 2.2 in the right lung, and 1: 2.4: 1.9 in the left lung. In both sitting and right side-lying, ventilation was distributed more to the middle than to the basal region, which may be related to age-associated changes in the respiratory system.


The non-canonical NF-κB pathway is induced by cytokines in pancreatic beta cells and contributes to cell death and proinflammatory responses in vitro.
Activation of the transcription factor nuclear factor (NF)-κB by proinflammatory cytokines plays an important role in beta cell demise in type 1 diabetes. Two main signalling pathways are known to activate NF-κB, namely the canonical and the non-canonical pathways. Up to now, studies on the role of NF-κB activation in beta cells have focused on the canonical pathway. The aim of this study was to investigate whether cytokines activate the non-canonical pathway in beta cells, how this pathway is regulated and the consequences of its activation on beta cell fate. NF-κB signalling was analysed by immunoblotting, promoter reporter assays and real-time RT-PCR, after knockdown or overexpression of key genes/proteins. INS-1E cells, FACS-purified rat beta cells and the human beta cell line EndoC-βH1 exposed to cytokines were used as models. IL-1β plus IFN-γ induced stabilisation of NF-κB-inducing kinase and increased the expression and cleavage of p100 protein, culminating in the nuclear translocation of p52, the hallmark of the non-canonical signalling. This activation relied on different crosstalks between the canonical and non-canonical pathways, some of which were beta cell specific. Importantly, cytokine-mediated activation of the non-canonical pathway controlled the expression of 'late' NF-κB-dependent genes, regulating both pro-apoptotic and inflammatory responses, which are implicated in beta cell loss in early type 1 diabetes. The atypical activation of the non-canonical NF-κB pathway by proinflammatory cytokines constitutes a novel 'feed-forward' mechanism that contributes to the particularly pro-apoptotic effect of NF-κB in beta cells.


Enhancement of artificial magnetism via resonant bianisotropy.
All-dielectric "magnetic light" nanophotonics based on high refractive index nanoparticles allows controlling magnetic component of light at nanoscale without having high dissipative losses. The artificial magnetic optical response of such nanoparticles originates from circular displacement currents excited inside those structures and strongly depends on geometry and dispersion of optical materials. Here an approach for enhancing of magnetic response via resonant bianisotropy effect is proposed and analyzed. The key mechanism of enhancement is based on electric-magnetic interaction between two electrically and magnetically resonant nanoparticles of all-dielectric dimer. It was shown that proper geometrical arrangement of the dimer in respect to the incident illumination direction allows flexible control over all vectorial components of the magnetic moment, tailoring the latter in the dynamical range of 100% and delivering enhancement up to 36% relative to performances of standalone spherical particles. The proposed approach provides pathways for designs of all-dielectric metamaterials and metasurfaces with strong magnetic responses.


Cysteine proteases of parasitic organisms.
Cysteine proteases play numerous indispensable roles in the biology of parasitic organisms. Aside from previously known general catabolic functions and protein processing, cysteine proteases may be key to parasite immunoevasion, excystment/encystment, exsheathing and cell and tissue invasion. Parasite cysteine proteases are unusually immunogenic and have been exploited as serodiagnostic markers and vaccine targets. Although host homologues exist, parasite cysteine proteases have distinct structural and biochemical properties including, pH optima and stability, the alteration in peptide loops or domain extensions, diverse substrate specificity and cellular location. The disparate nature of parasite cysteine protease compared to the host orthologous proteins has opened opportunities for chemotherapy. This review will highlight recent research on the 'papain-like' class of cysteine proteases, the most abundant family, and the newly discovered class of asparaginyl-endopeptidases. Cysteine protease classification will be re-examined in light of the diversity uncovered within parasitic organisms.


Different acetonitrile degraders and degrading genes between anaerobic ammonium oxidation and sequencing batch reactor as revealed by stable isotope probing and magnetic-nanoparticle mediated isolation.
Microbial degraders play crucial roles in wastewater treatment processes, but their use is limited as most microbes are yet unculturable. Stable isotope probing (SIP) is a cultivation-independent technique identifying functional-yet-uncultivable microbes in ambient environment, but is unsatisfactory for substrates with low assimilation rate owing to the low isotope incorporation into DNA. In this study, we used acetonitrile as the target low-assimilation chemical in many wastewater treatment plants and attempted to identify the active acetonitrile degraders in the activated sludge, via DNA-SIP and magnetic-nanoparticle mediated isolation (MMI) which is another cultivation-independent approach without the requirement of substrate labeling. The two approaches identified different active acetonitrile degraders in a 3-day short-term anaerobic ammonium oxidation (ANAMMOX). MMI enriched significantly more acetonitrile-degraders than SIP, showing the advantages in identifying the active degraders for low-assimilation substrates. Sequencing batch reactor (SBR, 30-day degradation) helped in more incorporation of 15N-labeled acetonitrile into the active degraders, thus the same acetonitrile-degraders and acetonitrile-degrading genes were identified by SIP and MMI. Different acetonitrile degraders between ANAMMOX and SBR were attributed to the distinct hydrological conditions. Our study for the first time explored the succession of acetonitrile-degraders in wastewater and identified the active acetonitrile-degraders which could be further enriched for enhancing acetonitrile degradation performance. These findings provide new insights into the acetonitrile metabolic process in wastewater treatment plants and offer suggestive conclusions for selecting appropriate treatment strategy in wastewater management.


Integrative network fusion-based multi-omics study for biomarker identification and patient classification of rheumatoid arthritis.
Cold-dampness Syndrome (RA-Cold) and Hot-dampness Syndrome (RA-Hot) are two distinct groups of rheumatoid arthritis (RA) patients with different clinical symptoms based on traditional Chinese medicine (TCM) theories and clinical empirical knowledge. However, the biological basis of the two syndromes has not been fully elucidated, which may restrict the development of personalized medicine and drug discovery for RA diagnosis and therapy. An integrative strategy combining clinical transcriptomics, phenomics, and metabolomics data based on clinical cohorts and adjuvant-induced arthritis rat models was performed to identify novel candidate biomarkers and to investigate the biological basis of RA-Cold and RA-Hot. The main clinical symptoms of RA-Cold patients are joint swelling, pain, and contracture, which may be associated with the dysregulation of T cell-mediated immunity, osteoblast differentiation, and subsequent disorders of steroid biosynthesis and phenylalanine metabolism. In contrast, the main clinical symptoms of RA-Hot patients are fever, irritability, and vertigo, which may be associated with various signals regulating angiogenesis, adrenocorticotropic hormone release, and NLRP3 inflammasome activation, leading to disorders of steroid biosynthesis, nicotinamide, and sphingolipid metabolism. IL17F, 5-HT, and IL4I1 were identified as candidate biomarkers of RA-Cold, while S1P and GLNS were identified as candidate biomarkers of RA-Hot. The current study presents the most comprehensive metabonomic and transcriptomic profiling of serum, urine, synovial fluid, and synovial tissue samples obtained from RA-Cold and RA-Hot patients and experimental animal models to date. Through the integration of multi-omics data and clinical independent validation, a list of novel candidate biomarkers of RA-Cold and RA-Hot syndromes were identified, that may be useful in improving RA diagnosis and therapy.


Reelin and mDab1 regulate the development of hippocampal connections.
We analyze in this study the participation of Reelin and mDab1 in the development of hippocampal connections. We show that mDab1 is present in growth cones and axonal tracts of developing hippocampal afferents. mdab1-deficiency produces severe alterations in the entorhino-hippocampal and commissural connections identical to those described in reeler mice, including innervation of ectopic areas, formation of abnormal patches of fiber termination and a delay in the refinement of projections. Organotypic slice cultures combining tissue from mdab1-mutant and control mice demonstrate that the abnormalities observed in the mutant entorhino-hippocampal projection are caused by mdab1-deficiency in both the projecting neurons and target hippocampal cells. Axonal afferents that innervate the hippocampus react to Reelin by reducing axonal growth, and increasing growth cone collapse and axonal branching. Altogether these results indicate that Reelin and mDab1 participate in the development and refinement of hippocampal connections by regulating axonal extension, targeting and branching.


Eligibility for vericiguat in a real-world heart failure population according to trial, guideline and label criteria: Data from the Swedish Heart Failure Registry.
We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration ≥6 months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality.


Spousal Loss and Change in Cognitive Functioning: An Examination of Temporal Patterns and Gender Differences.
The study investigates whether the disadvantaged position of men in the adverse consequences of widowhood for health and mortality also exists for changes in cognitive health. We used data of up to 1,269 men and women aged 65 years and older who participated in the Longitudinal Aging Study Amsterdam in 3-yearly assessments between 1992 and 2012 (5,123 person-observations). All were married and without cognitive impairment (Mini-Mental State Examination ≥ 24) at baseline and up to 419 lost their spouse. In fixed effects regression models, the effect of spousal loss on change in four domains of cognitive functioning was estimated independently of age-related cognitive change. For women, a robust temporary decrease was found in the second year after spousal loss in the reasoning domain, but not in global cognitive functioning, processing speed, or memory. No robust effects were found for men. Considering that only one cognitive domain was affected and effects were temporary, cognitive functioning seems rather robust to the experience of spousal loss. Despite men having often been reported to be in a disadvantaged position in other health domains, our analyses indicate no such pattern for cognitive functioning.


Polyethylene Oxide Molecular Size Determines the Severity of Atypical Thrombotic Microangiopathy in a Guinea Pig Model of Acute Intravenous Exposure.
In 2017, Opana ER was voluntarily removed from the U.S. market based on concerns that its risks outweighed its therapeutic benefits. The data that supported this conclusion were based on postmarketing evaluation that demonstrated increased intravenous abuse associated outbreaks of HIV, hepatitis C, and uniquely, a thrombotic thrombocytopenic purpura (TTP)-like syndrome. In 2017, the cause was mechanistically linked to intravenous exposure of the high-molecular weight polyethylene oxide (PEO), an excipient component of the drug product. However, it was unknown how differing PEO preparations might alter this response in vivo. Knowing the likelihood of a PEO driven atypical thrombotic microangiopathy with hemolytic uremic syndrome (TMA-HUS), this study was specifically designed with the primary objective focused on understanding the impact of PEO molecular weight on TMA-HUS in a guinea pig model of acute repeat PEO (1, 4, and 7 MDa) dosing. Results from this analysis suggest that repeated dosing with PEO 4 and 7 MDa, but not 1 MDa induced a marked intravascular hemolysis with schistocytes, mild anemia, thrombocytopenia, hemoglobinuria, and kidney injury, consistent with observations of a TMA-HUS-like syndrome. Nonetheless, observations of tissue microthrombi, complement or altered von Willebrand factor involvement were not observed, which would be consistent with a definitive TMA. Further, only 7 MDa PEO dosing was associated with marked renal hypoxia. Taken together, this study defines renal injury risk with PEO formulations >1 MDa that is driven by a robust intravascular hemolysis and potentially, tissue hypoxia.


Schizophrenia as a self-disorder due to perceptual incoherence.
The aim of this review is to describe the potential relationship between multisensory disintegration and self-disorders in schizophrenia spectrum disorders. Sensory processing impairments affecting multisensory integration have been demonstrated in schizophrenia. From a developmental perspective multisensory integration is considered to be crucial for normal self-experience. An impairment of multisensory integration is called 'perceptual incoherence'. We theorize that perceptual incoherence may evoke incoherent self-experiences including depersonalization, ambivalence, diminished sense of agency, and 'loosening of associations' between thoughts, feelings and actions that lie within the framework of 'self-disorders' as described by Sass and Parnas (2003). We postulate that subconscious attempts to restore perceptual coherence may induce hallucinations and delusions. Increased insight into mechanisms underlying 'self-disorders' may enhance our understanding of schizophrenia, improve recognition of early psychosis, and extend the range of therapeutic possibilities.


A Rare Case of Colonic Triplication with Associated Imperforate Anus in a Newborn Male.
We present a case of a newborn male with imperforate anus who was found to have colonic triplication with a high rectovesical fistula. The case is presented with a focus on surgical strategies for the management of this rare malformation.


Patient choice systems and waiting times for scheduled services.
Access to scheduled healthcare is a continuing challenge. A synthesis of the international literature was conducted to examine the potential of patient choice systems to reduce waiting times in Canada. A multitude of factors appear to influence the actions and outcomes of patients, providers, and systems. For choice systems to be effective, there must be uptake, which requires incentives and supports. Choice should be considered as but one element of a comprehensive waiting time management strategy.


Prenatal dexamethasone exposure alters effort decision making and triggers nucleus accumbens and anterior cingulate cortex functional changes in male rats.
Daily, individuals select actions based on cost-benefit to allocate resources into goal-directed actions. Different brain regions coordinate this complex decision, including the nucleus accumbens (NAc), anterior cingulate cortex (ACC), and ventral tegmental area (VTA). In utero exposure to synthetic glucocorticoids (iuGC), such as dexamethasone, triggers prominent motivation deficits but the impact of this exposure in the ACC-NAc and/or ACC-VTA circuits is unknown. Here, we show that iuGC exposure causes decreased motivation for natural rewards (food) and impaired effort-based decision-making. Importantly, reduced neuronal activation (number of c-fos+ neurons) was observed in the NAc core and ACC of iuGC rats in comparison to CTR rats after performing the effort-based decision-making task. In addition, iuGC treatment led to increased NAc and ACC basal neuronal activity. Electrophysiological recordings during optogenetic modulation of ACC terminals in the NAc revealed that the ACC-NAc circuit is dysfunctional in iuGC animals. These data suggest that iuGC animals present motivational and effort-based decision-making deficits that can be associated with the observed ACC-NAc dysfunction.


The growth factor SVH-1 regulates axon regeneration in C. elegans via the JNK MAPK cascade.
The ability of neurons to undergo regenerative growth after injury is governed by cell-intrinsic and cell-extrinsic regeneration pathways. These pathways represent potential targets for therapies to enhance regeneration. However, the signaling pathways that orchestrate axon regeneration are not well understood. In Caenorhabditis elegans, the Jun N-terminal kinase (JNK) and p38 MAP kinase (MAPK) pathways are important for axon regeneration. We found that the C. elegans SVH-1 growth factor and its receptor, SVH-2 tyrosine kinase, regulate axon regeneration. Loss of SVH-1-SVH-2 signaling resulted in a substantial defect in the ability of neurons to regenerate, whereas its activation improved regeneration. Furthermore, SVH-1-SVH-2 signaling was initiated extrinsically by a pair of sensory neurons and functioned upstream of the JNK-MAPK pathway. Thus, SVH-1-SVH-2 signaling via activation of the MAPK pathway acts to coordinate neuron regeneration response after axon injury.


Light Triggers the miRNA-Biogenetic Inconsistency for De-etiolated Seedling Survivability in Arabidopsis thaliana.
The shift of dark-grown seedlings into light causes enormous transcriptome changes followed by a dramatic developmental transition. Here, we show that microRNA (miRNA) biogenesis also undergoes regulatory changes during de-etiolation. Etiolated seedlings maintain low levels of primary miRNAs (pri-miRNAs) and miRNA processing core proteins, such as Dicer-like 1, SERRATE, and HYPONASTIC LEAVES 1, whereas during de-etiolation both pri-miRNAs and the processing components accumulate to high levels. However, the levels of most miRNAs do not notably increase in response to light. To reconcile this inconsistency, we demonstrated that an unknown suppressor decreases miRNA-processing activity and light-induced SMALL RNA DEGRADING NUCLEASE 1 shortens the half-life of several miRNAs in de-etiolated seedlings. Taken together, these data suggest a novel mechanism, miRNA-biogenetic inconsistency, which accounts for the intricacy of miRNA biogenesis during de-etiolation. This mechanism is essential for the survival of de-etiolated seedlings after long-term skotomorphogenesis and their optimal adaptation to ever-changing light conditions.


[Contribution of immunology to the differentiation of arteritis in young persons. Apropos of 2 cases].
The authors report two observations of T.A.O. placed under the heading of "Systems Affections" after the discovery of immunologic abnormalities. Vascular troubles in L.E.A.D. and generalised sclerodermis are, apart from the Raynaud Syndrom, exceptional. They oriente specially towards a T.A.O., and in absence of caracteristic symptoms, they retard the diagnosis of a connective. The reader is reminded of the characteristics of the "Buerger Affection" which must no longer be considered as unique anatomoclinic entity, due to modern immunologic and phlebologic exams.


Heterogeneous mechanisms of autocrine growth of AML blasts.
The ability of blast cells to grow autonomously and to produce autostimulatory growth factors has been investigated in 25 consecutive patients with AML. An autostimulatory index (ASI) was calculated (no. of colonies without CSF divided by no. of colonies with CSF) and patients classified into four groups: Group 1 (n = 3): non-growers; Group 2 (n = 4): CSF-dependent (ASI less than 0.1); Group 3 (n = 11): partially autonomous (ASI 0.1-0.8); and Group 4 (n = 7): fully autonomous/CSF-unresponsive (ASI greater than 0.8). In Group 3 patients colony formation and DNA synthesis were significantly (P less than 0.01) augmented by CSFs but at high cell concentrations became CSF-independent. Blast cell-conditioned medium (BCCM) from these patients exhibited potent autostimulatory activity, increasing DNA synthesis by less than or equal to 5-fold, and also stimulated CSF-dependent homologous blasts by less than or equal to 20-fold. In 5/5 this activity was neutralized by anti-GM-CSF, which also inhibited autonomous proliferation of their blast cells. Group 4 blasts also secreted GM-CSF but their BCCM possessed no autostimulatory activity, and anti GM-CSF failed to inhibit their autonomous growth. No membrane-associated CSF activity was found, however purified cytosolic fractions stimulated proliferation of CSF-dependent homologous blasts, consistent with production and secretion of CSF which is present in active form in the cytosol but does not autostimulate via membrane receptors. These results suggest that autocrine mechanisms are important in regulating blast cell proliferation, but that the mechanisms are heterogeneous.


Identification of germination gene of Bacillus megaterium.
Glucose, KNO3, proline and leucine initiate the spore germination of B. megaterium ATCC 12872, but not of B. megaterium ATCC 19213. In order to isolate the gene concerning germination of B. megaterium ATCC 12872, we constructed its gene library in plasmid vector, and introduced into B. megaterium ATCC 19213. We obtained a transformant whose spores differed from those of the wild type strain with respect to germinability. Spores of this transformant could be germinated by glucose, proline or leucine. The recombinant plasmid prepared from this transformant was found to carry 2 kilobase pairs fragment of B. megaterium ATCC 12872 DNA. This fragment may contain the gene encoding the protein which plays an important role in germination.


Evaluation of microvessels in colorectal tumors by narrow band imaging magnification.
Narrow band imaging (NBI) uses optical filters for sequential green and blue illumination and narrows the bandwidth of spectral transmittance. We determined the clinical usefulness of NBI magnification for evaluation of microvascular architecture and qualitative diagnosis of colorectal tumors. This study was a retrospective study. Department of Endoscopy, Hiroshima University, Hiroshima, Japan. A total of 189 colorectal lesions were analyzed. Each lesion was observed by NBI magnifying endoscopy and classified according to microvascular features (ie, thickness and irregularity). Microvessel thickness was classified as invisible, thin, or thick, and microvessel irregularity was classified as invisible, regular, mildly irregular, or severely irregular. NBI endoscopic images were compared with histologic findings. With respect to microvessel thickness, invisible microvessels were found significantly more often in hyperplasia lesions, and thick microvessels were found significantly more often in carcinoma with submucosal massive invasion (sm-m) (P < .01). With respect to microvessel irregularity, invisible microvessels were found significantly often in hyperplasia lesions, and severely irregular microvessels were found significantly often in sm-m lesions (P < .01). Accuracy of diagnosis of sm-m on the basis of thick and severely irregular lesions was 100%. Microvascular features determined by NBI magnification are associated with histologic grade and depth of submucosal invasion. These results indicate that NBI magnification is useful for the prediction of histologic diagnosis and selection of therapeutic strategies of colorectal tumors.


Michigan Health & Hospital Association Keystone Obstetrics: a statewide collaborative for perinatal patient safety in Michigan.
Preventable harm to mothers and infants during labor and birth is a significant patient safety and professional liability issue. A Michigan Health & Hospital Association Keystone Center for Patient Safety & Quality Obstetric Collaborative Project involved perinatal teams from 15 Michigan hospitals during an 11-month period in 2009. The purpose of the project was to promote safe care practices during labor and birth using the Comprehensive Unit-based Safety Program (CUSP). Consistent with the CUSP model, this project's components included assessing and promoting a culture of safety; interdisciplinary team building; case review; learning from defects through multiple methods of education; team and individual coaching and peer encouragement; administrative support for the establishment of a fundamental safety infrastructure; and ongoing evaluation of care processes and outcomes. Study measures included 32 components of a perinatal patient infrastructure, 6 care processes during labor and birth, and 4 neonatal outcomes. Significant improvements were found in the safety culture (Safety Attitudes Questionnaire), the perinatal patient safety infrastructure components, and all care processes. Although the project was successful, getting buy-in from all members of the clinical team in each hospital for all of the measures was challenging at times. There was initial resistance to some of the measures and their various expected aspects of care. For example, some of the clinicians were initially reluctant to adopt the recommended standardized oxytocin protocol. Peer encouragement and unit-based feedback on progress in minimizing early elective births proved useful in many hospitals. A CUSP in obstetrics can be beneficial in improving the care of mothers and infants during labor and birth.


Clinical training in Ericksonian hypnosis.
The authors place great value on the role of experiential learning in their clinical trainings on Ericksonian approaches to hypnosis. This article describes several of the principal skill-building exercises used in their training programs. These highly practical exercises are intended to facilitate: (a) developing sensory acuity, (b) developing flexibility in forming and delivering suggestions, (c) employing naturalistic methods, (d) employing reframings, and (e) embedding suggestions. A rationale and goal for each exercise are also presented in order to help create an appropriate context for its use.


Implant-supported full-arch rehabilitation with immediate loading using two different digital impression techniques: a case report with 2-year follow-up.
Immediate full-arch loading is a highly complex and technique-sensitive procedure. Digital impression techniques aim to replace conventional analog systems to carry out dental treatments in a more predictive, safer, and less time-consuming way. This case report describes a patient with a guarded periodontal prognosis, who was rehabilitated with implant-supported fixed prostheses after full-mouth extractions. Immediate full-arch loading was performed by means of two digital impression systems: photogrammetric technology with PIC dental in the maxillary arch, and MedicalFit in the mandible. Immediate provisional prostheses in acrylic resin (polymethyl methacrylate) were milled and placed within 12 hours after implant placement surgeries. Both provisional structures fitted properly providing adequate esthetics and function. After the implant osseointegration period, final digital impressions were registered, and definitive zirconia full-arch implant-supported prostheses were delivered. The 24-month follow-up did not show biologic or mechanical complications.


Medication assessment tool to detect care issues from routine data: a pilot study in primary care.
Medication assessment tools (MATs) may be implemented in routine electronic data sources in order to identify patients with opportunities for optimisation of medication therapy management (MTM) and follow-up by a multi-disciplinary team. (1) To demonstrate the use of a MAT for cardiovascular conditions (MAT CVC) as a means of profiling potential opportunities for MTM optimisation in primary care and (2) to assess the performance of MAT CVC in identifying actual opportunities for better care. Members of a pharmacotherapy discussion group, i.e. two single-handed general practitioners (GPs), three GP partners, and community pharmacists (CPs) from each of two community pharmacies, in a rural part of the Netherlands. MAT CVC comprises 21 medication assessment criteria, each of which is designed to detect a specific care issue and to check whether it is 'addressed' by provision of guideline recommended care or 'open' in the presence ('open explained') or absence ('open unexplained') of pre-specified explanations for guideline deviations. (1) Relevant data was extracted from linked GP and CP electronic records and MAT CVC assessment was conducted to profile the population of CVC patients registered with both, participating CPs and GPs, in terms of 'open unexplained' care issues. (2) A purposive sample of patients with 'open unexplained' care issues was reviewed by each patient's GP. Number and proportion of 'open unexplained' care issues per MAT CVC criterion and per patient. The number of patients with MAT CVC detected 'open unexplained' care issues to be reviewed (NNR) in order to identify one that requires changes in MTM. In 1,876 target group patients, MAT CVC identified 6,915 care issues, of which 2,770 (40.1 %) were 'open unexplained'. At population level, ten MAT CVC criteria had particularly high potential for quality improvement. At patient level, 1,277 (68.1 %) target group patients had at least one 'open unexplained' care issue. For patients with four or more 'open unexplained' care issues, the NNR was 2 (95 % CI 2-2). The study demonstrates potential ways of using MA TCVC as a key component of a collaborative MTM system. Strategies that promote documentation and sharing of explanations for deviating from guideline recommendations may enhance the utility of the approach.


Perceived effectiveness of pictorial health warnings among Mexican youth and adults: a population-level intervention with potential to reduce tobacco-related inequities.
Pictorial health warnings on cigarette packages are a prominent and effective means of communicating the risks of smoking; however, there is little research on effective types of message content and socio-demographic effects. This study tested message themes and content of pictorial warnings in Mexico. Face-to-face surveys were conducted with 544 adult smokers and 528 youth in Mexico City. Participants were randomized to view 5-7 warnings for two of 15 different health effects. Warnings for each health effect included a text-only warning and pictorial warnings with various themes: "graphic" health effects, "lived experience", symbolic images, and testimonials. Pictorial health warnings were rated as more effective than text-only warnings. Pictorial warnings featuring "graphic" depictions of disease were significantly more effective than symbolic images or experiences of human suffering. Adding testimonial information to warnings increased perceived effectiveness. Adults who were female, older, had lower education, and intended to quit smoking rated warnings as more effective, although the magnitude of these differences was modest. Few interactions were observed between socio-demographics and message theme. Graphic depictions of disease were perceived by youth and adults as the most effective warning theme. Perceptions of warnings were generally similar across socio-demographic groups.


Immune activation in HIV-infected aging women on antiretrovirals--implications for age-associated comorbidities: a cross-sectional pilot study.
Persistent immune activation and microbial translocation associated with HIV infection likely place HIV-infected aging women at high risk of developing chronic age-related diseases. We investigated immune activation and microbial translocation in HIV-infected aging women in the post-menopausal ages. Twenty-seven post-menopausal women with HIV infection receiving antiretroviral treatment with documented viral suppression and 15 HIV-negative age-matched controls were enrolled. Levels of immune activation markers (T cell immune phenotype, sCD25, sCD14, sCD163), microbial translocation (LPS) and biomarkers of cardiovascular disease and impaired cognitive function (sVCAM-1, sICAM-1 and CXCL10) were evaluated. T cell activation and exhaustion, monocyte/macrophage activation, and microbial translocation were significantly higher in HIV-infected women when compared to uninfected controls. Microbial translocation correlated with T cell and monocyte/macrophage activation. Biomarkers of cardiovascular disease and impaired cognition were elevated in women with HIV infection and correlated with immune activation. HIV-infected antiretroviral-treated aging women who achieved viral suppression are in a generalized status of immune activation and therefore are at an increased risk of age-associated end-organ diseases compared to uninfected age-matched controls.


Evaluation of health-care utilization in patients with Dravet syndrome and on adjunctive treatment with stiripentol and clobazam.
Dravet syndrome (DS) is a rare, severe childhood epilepsy syndrome that imposes a substantial burden on patients and their caregivers. This study evaluated health-care utilization over a 2-year period in patients with DS at an outpatient clinic of a German epilepsy center. Data on the course of epilepsy, anticonvulsant treatment, and direct costs were recorded using the electronic seizure diary Epivista and patients' files. We enrolled 13 patients with DS (6 females, mean age: 12.3±7.5 years) between 2007 and 2010 and evaluated them during a 1-year baseline. All patients had drug-resistant epilepsy and their seizures failed to improve with a mean number of 6.7±3.4 anticonvulsants. They had an overall mean seizure frequency of 102.1 seizures per year (median: 31, range: 3-538) with 43.2 GTCSs per year (median: 14, range: 0-228). We estimated the annual total direct costs at €6506±3974 (range: €1174-11,783) per patient with hospitalization (68.9% of total direct costs) as the major cost factor ahead of costs for anticonvulsants (24.0%). For the 1-year follow-up period, less severely affected patients were continued on conventional anticonvulsants (n=4) or switched to adjunctive treatment with stiripentol and clobazam (n=9). In the latter group, six patients (67%) were long-term responders, with between 25% and 100% seizure reduction with respect to either GTCSs or the overall seizure frequency. This reduction in seizure frequency was associated with a shift in the distribution of cost components towards higher medication costs and decreased hospitalization costs. The total direct costs increased by 42.7%, mainly due to the newly introduced stiripentol, with an annual cost of €6610. This study showed that direct costs of patients with DS were above the average European costs of drug-resistant epilepsy in children. Treatment with new anticonvulsants resulted in reduction of seizures and inpatient admissions.


[Cardiac consequences of clinical dysthyroidism. Pathophysiological, clinical, and epidemiologic data].
Thyroid hormones affect the vascular system, including the diastolic and systolic functioning of the heart. Resting heart rate increases early in hyperthyroidism (cardiac contractility expands due to improved ventricular loading and decreased systemic vascular resistance). Paradoxically, these hemodynamic alterations progressively reduce cardiac performance on effort (changes in diastolic, then systolic functioning) and finally at rest (modification in ventricular loading following tachycardia or atrial fibrillation), especially in cases of underlying heart disease (in the elderly). Hypothyroidism has an inverse hemodynamic effect and is less noisy, usually limited to relative bradycardia. The morbidity and mortality associated with hypothyroidism are apparently related to the atherogenic and prothrombotic vascular modifications that follow thyroid hormone deficiency, whereas heart failure and particularly atrial fibrillation and its thromboembolic complications are the primary consequences of hyperthyroidism. In both cases, return to normal thyroid levels corrects the cardiac abnormalities caused by the dysthyroidism. Dysthyroidism (hypo- or hyperthyroidism) occurs in 10 to 20% of the patients treated with amiodarone for arrhythmia. Because of its potential seriousness, some clinical or laboratory tests are necessary before initiating treatment, and specific clinical surveillance should be scheduled, including laboratory tests.