Effect of liposome-encapsulated hemoglobin resuscitation on proteostasis in small intestinal epithelium after hemorrhagic shock.
Gut barrier dysfunction is the major trigger for multiorgan failure associated with hemorrhagic shock (HS). Although the molecular mediators responsible for this dysfunction are unclear, oxidative stress-induced disruption of proteostasis contributes to the gut pathology in HS. The objective of this study was to investigate whether resuscitation with nanoparticulate liposome-encapsulated hemoglobin (LEH) is able to restore the gut proteostatic mechanisms. Sprague-Dawley rats were recruited in four groups: control, HS, HS+LEH, and HS+saline. HS was induced by withdrawing 45% blood, and isovolemic LEH or saline was administered after 15 min of shock. The rats were euthanized at 6 h to collect plasma and ileum for measurement of the markers of oxidative stress, unfolded protein response (UPR), proteasome function, and autophagy. HS significantly increased the protein and lipid oxidation, trypsin-like proteasome activity, and plasma levels of IFNγ. These effects were prevented by LEH resuscitation. However, saline was not able to reduce protein oxidation and plasma IFNγ in hemorrhaged rats. Saline resuscitation also suppressed the markers of UPR and autophagy below the basal levels; the HS or LEH groups showed no effect on the UPR and autophagy. Histological analysis showed that LEH resuscitation significantly increased the villus height and thickness of the submucosal and muscularis layers compared with the HS and saline groups. Overall, the results showed that LEH resuscitation was effective in normalizing the indicators of proteostasis stress in ileal tissue. On the other hand, saline-resuscitated animals showed a decoupling of oxidative stress and cellular protective mechanisms.


The Relationship Between Busulfan Exposure and Achievement of Sustained Donor Myeloid Chimerism in Patients with Non-Malignant Disorders.
The overall objective of allogeneic hematopoietic cell transplantation (HCT) in patients with non-malignant conditions involves replacing a dysfunctional or absent cell or gene product for disease correction. It is unclear whether lower busulfan exposure may be sufficient in this population to facilitate durable myeloid engraftment and limit toxicity. Given that neither the ideal level of mixed myeloid chimerism for specific non-malignant diseases nor how to condition a patient to achieve stable mixed myeloid chimerism is fully known, we sought to analyze the relationships among busulfan exposure, myeloid chimerism, and outcomes in patients with non-malignant conditions receiving busulfan as a part of combination pretransplant conditioning at our institution. This was a single-center, retrospective study including pediatric patients with a variety of non-malignant disorders who underwent allogeneic HCT at the University of California San Francisco Benioff Children's Hospital from March 2007 to June 2018. The busulfan cumulative area under the curve (cAUC) was estimated using a validated population pharmacokinetic model and nonlinear mixed effects modeling. Median busulfan cAUC for all patients was 70 mg·h/L (range, 53 to 108). All of the 29 patients with a busulfan cAUC of ≥70 mg·h/L achieved long-term disease correction with full or stable mixed (>20%) myeloid chimerism, compared to 78.5% (22/28) of patients with a cAUC of <70 mg·h/L (P = .01). Overall ksurvival was evaluated up to 3 years and was identical in patients with busulfan cAUC < 70 mg·h/L and patients with busulfan cAUC ≥70 mg·h/L (96% versus 93%; P = .92). Only three patients died, at days 65, 164 and 980 days post-HCT. Severe busulfan-related toxicities and graft-versus-host-disease (GVHD) were rare, with veno-occlusive disease occurring in four patients (7%), acute respiratory distress syndrome in three patients (5%), and GVHD in five patients (9%). These results demonstrate excellent outcomes and extremely low rates of toxicity across our entire cohort. Based on the results of this study, we recommend a busulfan exposure target of 75 mg·h/L (range, 70 to 80) in all non-malignant patients receiving allogeneic HCT to ensure optimal exposure for achievement of high-level stable myeloid chimerism.


Multidrug resistance and efflux pumps: insights from molecular dynamics simulations.
Evolution of bacteria resistant to the most diverse antibiotics is posing one of the major threats to public health. Particular alarm is raised by those genetic lines that develop phenotypes simultaneously resistant to multiple drugs. Among the different mechanisms leading to multidrug resistance, multidrug efflux pumps raise particular concern. These are large macromolecular constructs localised at cell boundaries, which are able to actively bind and transport out of the cell several chemically uncorrelated substrates. In this last decade, computer modelling has proved to be a valuable tool for the investigation of multiple drug-efflux systems at the molecular level. In particular, molecular dynamics simulations unveiled several aspects of the molecular mechanisms governing the recognition and transport of drugs by these systems. Computer-aided protocols constitute a bottom-up reductionist approach that has the privilege of obtaining clean data referring intrinsically to those single parts of the efflux process explicitly taken into account. Combining computational data to the experimental determinations may therefore help in the definition of possible general criteria limiting the action of these systems against both patented and new putative antibiotic agents. Here, we review the most relevant contributions by computational scientists to the understanding of multidrug-efflux systems in the recent past. Particular care is put in the description of the dynamical features of multidrug exporters, a valuable piece of information for which computer modelling represents one of the best investigation tools available at present.


[Continuous synchronously dividing cultures of the B meningococcus serogroup].
Cultures of Neisseria meningitidis Bc5S No. 125 with continuous and synchronous cell fission have been obtained. The synchronization index is 0.59-0.63. The synthesis of protein at different periods of the synchronized cycle occurs at constant speed. The synthesis of RNA and DNA is periodical, the maximum accumulation of DNA occurring at the period prior to cell fission. The amount of polysaccharide in the whole culture and the cells is considerably greater than in the supernatant fluid. At the period of fission the content of polysaccharide per 1 billion cells decreases. The indices characterizing the increase of biomass, the synthesis of macromolecular compositions and polysaccharide, the titers of the reaction of agglutination remain unchanged during the whole period of cultivation, which is indicative of the stability of the continuous and synchronous process. The use of this process holds considerable promise for obtaining N. meningitidis synchronized cultures in large amounts, for the study of the biological properties of meningococci and for obtaining immunoprophylactic preparations.


The extent of blockade following axillary and infraclavicular approaches of brachial plexus block in uremic patients.
This study was aimed to compare the axillary approach performed through multiple injection method and vertical infraclavicular approach performed through single injection method in terms of the sensory and motor block onset, quality, and extent of blocks of brachial plexus in uremic patients who underwent arteriovenous fistula surgery. Forty patients scheduled for creation of arteriovenous fistula with axillary brachial plexus block (group AX, n = 20) or infraclavicular brachial plexus block (IC group, n = 20) were examined. The median, radial, ulnar, and musculocutaneous nerves were selectively localized by nerve stimulation. The volume of the local anesthetics was calculated based on the height of each patient, and the volume determined was prepared by mixing 2% lidocaine and 0.5% bupivacaine in equal proportions. Sensory and motor block were assessed at 3, 6, 9, 12, 15, 18, and 30th min and their durations were measured. While the adequate sensory and motor block rate with axillary approach was 100% in musculocutaneous, median, radial, ulnar and medial antebrachial cutaneous nerves, it was 65% in axillary nerve, 80% in intercostobrachial nerve and 95% in medial brachial cutaneous nerve. This rate was found to be 100% for all the nerves with infraclavicular approach. For arteriovenous fistula surgeries in uremic patients, both axillary approach performed through multiple injection method and vertical infraclavicular approach performed through single injection method can be used successfully; however, for the short performance of the procedure, infraclavicular block may be preferred. Brachial plexus block; Axillary; Infraclavicular; Uremic patients.


Molecular mechanisms of cardioprotective effects mediated by transplanted cardiac ckit+ cells through the activation of an inflammatory hypoxia-dependent reparative response.
The regenerative effects of cardiac ckit+ stem cells (ckit+CSCs) in acute myocardial infarction (MI) have been studied extensively, but how these cells exert a protective effect on cardiomyocytes is not well known. Growing evidences suggest that in adult stem cells injury triggers inflammatory signaling pathways which control tissue repair and regeneration. Aim of the present study was to determine the mechanisms underlying the cardioprotective effects of ckit+CSCs following transplantation in a murine model of MI. Following isolation and in vitro expansion, cardiac ckit+CSCs were subjected to normoxic and hypoxic conditions and assessed at different time points. These cells adapted to hypoxia as showed by the activation of HIF-1α and the expression of a number of genes, such as VEGF, GLUT1, EPO, HKII and, importantly, of alarmin receptors, such as RAGE, P2X7R, TLR2 and TLR4. Activation of these receptors determined an NFkB-dependent inflammatory and reparative gene response (IRR). Importantly, hypoxic ckit+CSCs increased the secretion of the survival growth factors IGF-1 and HGF. To verify whether activation of the IRR in a hypoxic microenvironment could exert a beneficial effect in vivo, autologous ckit+CSCs were transplanted into mouse heart following MI. Interestingly, transplantation of ckit+CSCs lowered apoptotic rates and induced autophagy in the peri-infarct area; further, it reduced hypertrophy and fibrosis and, most importantly, improved cardiac function. ckit+CSCs are able to adapt to a hypoxic environment and activate an inflammatory and reparative response that could account, at least in part, for a protective effect on stressed cardiomyocytes following transplantation in the infarcted heart.


Analysis of administrative data finds endoscopist quality measures associated with postcolonoscopy colorectal cancer.
Most quality indicators for colonoscopy measure processes; little is known about their relationship to patient outcomes. We investigated whether characteristics of endoscopists, determined from administrative data, are associated with development of postcolonoscopy colorectal cancer (PCCRC). We identified individuals diagnosed with colorectal cancer in Ontario from 2000 to 2005 using the Ontario Cancer Registry. We determined performance of colonoscopy using Ontario Health Insurance Plan data. Patients who had complete colonoscopies 7 to 36 months before diagnosis were defined as having a PCCRC. Patients who had complete colonoscopies within 6 months of diagnosis had detected cancers. We determined if endoscopist factors (volume, polypectomy and completion rate, specialization, and setting) were associated with PCCRC using logistic regression, controlling for potential covariates. In the study, 14,064 patients had a colonoscopy examination within 36 months of diagnosis; 584 (6.8%) with distal and 676 (12.4%) with proximal tumors had PCCRC. The endoscopist's specialty (nongastroenterologist/nongeneral surgeon) and setting (non-hospital-based colonoscopy) were associated with PCCRC. Those who underwent colonoscopy by an endoscopist with a high completion rate were less likely to have a PCCRC (distal: odds ratio [OR], 0.73; 95% confidence interval [CI], 0.54-0.97; P = .03; proximal: OR, 0.72; 95% CI, 0.53-0.97; P = .002). Patients with proximal cancers undergoing colonoscopy by endoscopists who performed polypectomies at high rates had a lower risk of PCCRC (OR, 0.61; 95% CI, 0.42-0.89; P < .0001). Endoscopist volume was not associated with PCCRC. Endoscopist characteristics derived from administrative data are associated with development of PCCRC and have potential use as quality indicators.


Broiler Chicken Behavior and Activity Are Affected by Novel Flooring Treatments.
The objective was to determine broiler chicken behavioral differences in response to novel flooring treatments. Broilers (n = 182) were housed in 14 pens (a random subset from a larger-scale study including 42 pens), with 13 birds/pen. One of seven flooring treatments were randomly allocated to 14 pens (2 pens per treatment). The flooring treatments (provided from day 1 {1} or day 29 {29}) included regularly replaced shavings (POS), a mat with 1% povidone-iodine solution (MAT), and the iodine mat placed on a partially slatted floor (SLAT). In addition, a negative control treatment was included with birds kept on used litter from day 1 (NEG). Behavior was recorded in weeks 1, 2, 5, and 6. In week 5, treatments affected the behavioral repertoire (p ≤ 0.035). Birds in POS-1 showed more locomoting, preening and activity overall compared to MAT and/or SLAT treatments. Birds in POS-29 showed more drinking, foraging, preening and overall activity than birds in MAT and/or SLAT treatments. In week 6, birds in the POS-1 treatment spent more time foraging compared to birds in all MAT and SLAT treatments (p ≤ 0.030). In addition, birds in the POS-1 treatment spent more time preening than birds in the MAT-1 treatment (p = 0.046). Our results indicate that access to partially slatted flooring and/or disinfectant mats does not benefit broiler chicken welfare in terms of their ability to express highly motivated behaviors. Access to clean, regularly replaced litter is beneficial for broiler chicken welfare in terms of their ability to express their normal behavioral repertoire.


Empowering self-direction in return to work of employees with low and high levels of education: A qualitative comparative study.
Dutch legislation encourages active participation of employees in their return-to-work (RTW) process. Empowering leadership may support employees' self-direction in this process (i.e. by allowing and enabling their involvement in decision-making). Building upon a previous study, we aimed to study (1) how representatives of a university, i.e. an employer for employees with high levels of education (EH), manage RTW, (2) the similarities and differences between the RTW management of employers (or representatives thereof) of employees with low (EL) and high levels of education, and (3) the degree to which the employers' roles resemble empowering leadership. Qualitative methodology was applied. A thematic analysis of interview transcripts (rq1) was followed by a comparison of themes (rq2) and pattern matching (rq3). (1) EH tend to engage in dialogue and accommodate their employees as much as possible. (2) EL and EH showed several similarities, such as aiming to meet legal requirements on RTW management. Compared to EL, EH tend to focus more on facilitating employees. (3) Empowering leadership seems to be more common among EH. Compared to employees with low levels of education, those with high levels of education may be granted more opportunity to self-direct their RTW. The study results provide starting points for employers for employees with both low and high levels of education who aim to enable employees' self-direction in RTW, and help them to develop empowering leadership styles.


[Effect of myocardial infarct on the cholinoreactivity of the heart atria and on their acetylcholine content].
The effect of left ventricular experimental infarction (caused by left coronary artery ligation) on the isolated right atrium contractile function and acetylcholine content in both atria was studied in male Wistar rats. It was shown that a 24-hour infarction induced an increase in atrial chronotropic response to acetylcholine, which proved an increase in the pacemaker cholinoreactivity. Atrial inotropic response to acetylcholine characterizing the contractile myocardium cholinoreactivity remained unchanged. At the same time atrial endogenous acetylcholine content decreased fourfold. An increase in pacemaker cholinoreactivity was not accompanied by changes in its adrenoreactivity; those changes increased the pacemaker sensitivity to cholinergic influences which could help elucidate the ectopic excitation foci, thus promoting the onset of arrhythmia.


Incomplete lineage sorting and ancient admixture, and speciation without morphological change in ghost-worm cryptic species.
Morphologically similar species, that is cryptic species, may be similar or quasi-similar owing to the deceleration of morphological evolution and stasis. While the factors underlying the deceleration of morphological evolution or stasis in cryptic species remain unknown, decades of research in the field of paleontology on punctuated equilibrium have originated clear hypotheses. Species are expected to remain morphologically identical in scenarios of shared genetic variation, such as hybridization and incomplete lineage sorting, or in scenarios where bottlenecks reduce genetic variation and constrain the evolution of morphology. Here, focusing on three morphologically similar Stygocapitella species, we employ a whole-genome amplification method (WGA) coupled with double-digestion restriction-site associated DNA sequencing (ddRAD) to reconstruct the evolutionary history of the species complex. We explore population structure, use population-level statistics to determine the degree of connectivity between populations and species, and determine the most likely demographic scenarios which generally reject for recent hybridization. We find that the combination of WGA and ddRAD allowed us to obtain genomic-level data from microscopic eukaryotes (∼1 millimetre) opening up opportunities for those working with population genomics and phylogenomics in such taxa. The three species share genetic variance, likely from incomplete lineage sorting and ancient admixture. We speculate that the degree of shared variation might underlie morphological similarity in the Atlantic species complex.


[Administration of oral vitaprost for prevention of exacerbations of chronic abacterial prostatitis].
Active substance of vitaprost is a complex of water-soluble biologically active peptides isolated from bovine prostate. The prostatic extract has an organotropic action in relation to the prostate. As all peptide bioregulators, prostatic extract has antiaggregant and anticoagulant properties, enhances synthesis of antihistamine and antiserotonine antibodies, improves microcirculation in the prostatic gland. This accounts for its ability to reduce edema in prostatic inflammation. This clinical trial demonstrated that vitaprost tablets decreases twice probability of chronic prostatitis exacerbation, of development of secondary exacerbations. A prophylactic intake of vitaprost relieves symptoms of chronic prostatitis, first of all pain (discomfort), improvement of quality of life by NIH-CPSI, including exacerbation and significantly reduces size of the prostate. Vitaprost tablets can be effectively used prophylactively in chronic prostatitis for reducing probability of the disease exacerbations and their severity.


Identification and characterization of the promoter region of Kaposi's sarcoma-associated herpesvirus ORF11.
Open reading frame 11 (ORF11) of Kaposi's sarcoma-associated herpesvirus belongs to a herpesviral homologous protein family that is conserved among members of the gamma-herpesvirus subfamily. Little is known about the function of ORF11 and how this viral gene is regulated in KSHV life cycle. In this study, we have characterized the major transcript of the ORF11 gene, which is located adjacent and in the opposite orientation to a well-characterized viral IL-6 gene. Northern blot analysis revealed that the ORF11 gene is lytic viral gene with delayed-early expression kinetics. We have determined the 5' and 3' untranslated region of the unspliced ORF11 transcript and identified both the transcription start site and the transcription termination site. Core promoter region, representing ORF11 promoter activity, was mapped to a 160nt fragment 5' most proximal to the transcription start site. A functional TATA box was identified in the core promoter region. We also found that the characterized ORF11 gene promoter region is not responsive to Rta, the KSHV lytic switch protein. Our data help to elucidate transcription regulation of the KSHV ORF11 gene and to understand the biology of ORF11 in KSHV life cycle.


Drug-resistance in multiple myeloma and non-Hodgkin's lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy.
The B-cell neoplasms, multiple myeloma and non-Hodgkin's lymphoma, frequently become drug resistant, despite initial responses to chemotherapeutic drugs. Tumor cells from eight patients with clinically drug-refractory disease were evaluated by immuno-histochemical staining for monoclonal immunoglobulin (Ig) expression, nuclear proliferation antigen, P-glycoprotein (P-gly) expression, and other cellular antigens. P-gly was detected on tumor cells from six of eight patients with drug-resistant disease. Of the six patients with P-gly-positive tumors, five patients had advanced multiple myeloma and one had a drug-refractory non-Hodgkin's lymphoma. Cellular RNA analysis confirmed the over-expression of P-gly. In an effort to overcome drug resistance, a pilot study evaluated possible verapamil enhancement of chemotherapy in these eight patients. All patients had developed progressive disease while receiving a regimen containing vincristine and doxorubicin, and seven of eight patients had previously received continuous infusion vincristine and doxorubicin plus oral dexamethasone (VAD). At the time of progressive disease, continuous infusion verapamil was added to the VAD regimen. Three of the eight patients who were refractory to vincristine and doxorubicin alone responded when verapamil was added to VAD. The three patients who responded had P-gly-positive tumors. Verapamil increased the intracellular accumulation of doxorubicin and vincristine in vitro for both a P-gly-positive myeloma cell line and tumor cells from two patients with end-stage myeloma which over-expressed P-gly. The dose-limiting side effect associated with the addition of verapamil to chemotherapy was temporary impairment of cardiac function, manifest as hypotension and cardiac arrhythmia. We conclude that P-gly expression occurs in drug-refractory B-cell neoplasms and may contribute to the development of clinical drug resistance. However, other factors, such as the proliferative activity of the tumor, may also play a role in determining response to chemotherapy. The administration of verapamil along with VAD chemotherapy may partially circumvent drug resistance in patients whose tumors over-express P-gly.


Three-Dimensional Pharyngeal Airway Changes After 2-Jaw Orthognathic Surgery With Segmentation in Dento-Skeletal Class III Patients.
To investigate short- and long-term three-dimensional changes of pharyngeal airway morphology and hyoid bone position in dento-skeletal class III deformity patients after 2-jaw orthognathic surgery with segmentation. A retrospective analysis has been performed on patients with dento-skeletal class III deformity who had undergone orthognathic 2-jaw surgery with segmentations, presenting both pre- and post-surgical cone-beam computed tomographys. Three-dimensional skeletal movements, pharyngeal airway changes and hyoid bone position were measured and correlated. The mean short term postsurgical review period for all included 47 patients was 5.8 ± 2.2 months. Thirteen patients among them provided a mean long term period of 26.4 ± 3.4 months. The mean postsurgical maxillary movement was 2.29 ± 2.49 mm in vertical, 2.02 ± 3.45 mm in horizontal direction, respectively, while the mandibular movement was 6.49 ± 4.58 mm in vertical, and -5.85 ± 6.13 mm in horizontal direction. In short-term, the vertical length of nasopharynx was found to be reduced (P = 0.005) but increased for the oropharynx (P < 0.001). Furthermore, the oropharyngeal minimum cross-sectional area has decreased significantly (P = 0.013). The hyoid bone moved posterosuperiorly, however, with only its horizontal movement found to be significant (P = 0.043). No significant result was detected in long-term analyses, neither in postsurgical pharyngeal airway changes nor the hyoid bone movement. There were no significant differences in pharyngeal airway measurements (P > 0.05) detected between patients with and without genioplasty advancement. Two-jaw orthognathic surgery in dento-skeletal class III patients led to a statistically non-significant reduction of the post-surgical airway volume in both short- and long-term. Although the post-surgical oropharyneal minimum cross-sectional area was decreased significantly in the short term, this finding did not persist in the long term.


[Activity of enzymes of glycolysis and gluconeogenesis in primary hepatomas induced by diethylnitrosamine].
Activities of the key enzymes of glycolysis and gluconeogenesis were studied in soluble fraction of primary hepatoma, induced by diethyl nitrosamine (DENA) in rats and mice of C3HA strain. Histological structure of the tumors studied showed that they belonged mainly to highly differentiated hepatocellular adenomas. Liver tissue of the animals which were not treated with DENA, was used as a control. The hexokinase activity was increased about 2-fold in the rat hepatomas and 3-fold--in the mice hepatomas. In primary hepatomas the glucokinase activity was unaltered or slightly decreased; the fructokinase activity was distinctly decreased (in several cases down to zero). The activity of key enzymes of gluconeogenesis--glucose-6-phosphatase and fructose-1,6-diphosphatase--was distinctly decreased, especially the activity of the former enzyme, which constituted in hepatomas about 1/6 of the activity found in liver tissue.


The Effect of Aromatherapy Application on Cognitive Functions and Daytime Sleepiness in Older Adults Living in a Nursing Home.
Changes in the aging process affect the duration and quality of sleep. Not having a quality night's sleep leads to a reduction in daytime wakefulness in older adults. We examined the effect of aromatherapy on the cognitive functions and daytime sleepiness of older adults living in a nursing home. The research was a pretest and posttest design, which was conducted without a control group. The sample included 39 elders. A rosemary-lemon oil mixture was smelled by elders in the mornings for a week. After a 1-week washout period, lavender oils were smelled in the evenings for a week. After application of the rosemary-lemon oil mixture, the mean score of participants' daytime sleepiness was lower, but that decline was not statistically meaningful (P > .050). After the same application, the mean score of the participants' cognitive functions was significantly lower (P < .001). After application of lavender oil, the scores were significantly lower (P < .001). Lower scores on the scales used indicate lower sleepiness. The results showed that the 2 applications can be used to improve cognitive functions in older adults; in addition, lavender oil has an advantage in reducing daytime sleepiness.


Periodontal disease progression in type II non-insulin-dependent diabetes mellitus patients (NIDDM). Part I--Probing pocket depth and clinical attachment.
Periodontal disease progression of 30 type II diabetic patients (NIDDM) and 30 patients in whom diabetes was not detected was evaluated. Age ranged from 30 to 77 years. To determine the periodontal condition, probing pocket depth and periodontal attachment loss were measured; to determine the metabolic control of the patients, glycosylated hemoglobin and fasting glucose were measured. At the end of the study, the diabetic group was divided into three subgroups, according to the metabolic state of the patients: controlled patients, moderately controlled patients, and poorly controlled patients. Comparing the diabetic and the control groups as a whole, there was no statistically significant difference in probing pocket depth, but significance (P < 0.01) was observed for attachment loss. When diabetic patients were divided into subgroups, significant differences were observed between the poorly controlled and the control groups (P < 0.01) for both the probing pocket depth and periodontal attachment. The glycosylated hemoglobin test was more reliable than the fasting glucose analysis.


The gap between estimated incidence of end-stage renal disease and use of therapy.
Relatively few data exist on the burden of end-stage renal disease (ESRD) and use of renal replacement therapy (RRT)-a life-saving therapy-in developing regions. No study has quantified the proportion of patients who develop ESRD but are unable to access RRT. We performed a comprehensive literature search to estimate use and annual initiation of RRT worldwide, and present these estimates according to World Bank regions. We also present estimates of survival and of etiology of diseases in patients undergoing RRT. Using data on prevalence of diabetes and hypertension, we modeled the incidence of ESRD related to these risk factors in order to quantify the gap between ESRD and use of RRT in developing regions. We find that 1.9 million patients are undergoing RRT worldwide, with continued use and annual initiation at 316 and 73 per million population respectively. RRT use correlates directly (Pearson's r = 0.94) with regional income. Hemodialysis remains the dominant form of RRT but there is wide regional variation in its use. With the exception of the Latin American and Caribbean region, it appears that initiation of RRT in developing regions is restricted to fewer than a quarter of patients projected to develop ESRD. This results in at least 1.2 million premature deaths each year due to lack of access to RRT as a result of diabetes and elevated blood pressure and as many as 3.2 million premature deaths due to all causes of ESRD. Thus, the majority of patients projected to reach ESRD due to diabetes or hypertension in developing regions are unable to access RRT; this gap will increase with rising prevalence of these risk factors worldwide.


Headache: What to ask, how to examine, and which scales to use. Recommendations of the Spanish Society of Neurology's Headache Study Group.
Headache is the most common neurological complaint at the different levels of the healthcare system, and clinical history and physical examination are essential in the diagnosis and treatment of these patients. With the objective of unifying the care given to patients with headache, the Spanish Society of Neurology's Headache Study Group (GECSEN) has decided to establish a series of consensus recommendations to improve and guarantee adequate care in primary care, emergency services, and neurology departments. With the aim of creating a practical document, the recommendations follow the dynamics of a medical consultation: clinical history, physical examination, and scales quantifying headache impact and disability. In addition, we provide recommendations for follow-up and managing patients' expectations of the treatment. With this tool, we aim to improve the care given to patients with headache in order to guarantee adequate, homogeneous care across Spain.


Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism.
Defects in genes mediating thyroid hormone biosynthesis result in dyshormonogenic congenital hypothyroidism (CH). Here, we report homozygous truncating mutations in SLC26A7 in 6 unrelated families with goitrous CH and show that goitrous hypothyroidism also occurs in Slc26a7-null mice. In both species, the gene is expressed predominantly in the thyroid gland, and loss of function is associated with impaired availability of iodine for thyroid hormone synthesis, partially corrected in mice by iodine supplementation. SLC26A7 is a member of the same transporter family as SLC26A4 (pendrin), an anion exchanger with affinity for iodide and chloride (among others), whose gene mutations cause congenital deafness and dyshormonogenic goiter. However, in contrast to pendrin, SLC26A7 does not mediate cellular iodide efflux and hearing in affected individuals is normal. We delineate a hitherto unrecognized role for SLC26A7 in thyroid hormone biosynthesis, for which the mechanism remains unclear.


From Doctor to Nurse Triage in the Danish Out-of-Hours Primary Care Service: Simulated Effects on Costs.
Introduction. General practitioners (GP) answer calls to the Danish out-of-hours primary care service (OOH) in Denmark, and this is a subject of discussions about quality and cost-effectiveness. The aim of this study was to estimate changes in fee costs if nurses substituted the GPs. Methods. We applied experiences from The Netherlands on nurse performance in the OOH triage concerning the number of calls per hour. Using the 2011 number of calls in one region, we examined three hypothetical scenarios with nurse triage and calculated the differences in fee costs. Results. A new organisation with 97 employed nurses would be needed. Fewer telephone consultations may result in an increase of face-to-face contacts, resulting in an increase of 23.6% in costs fees. Under optimal circumstances (e.g., a lower demand for OOH services, a high telephone termination rate, and unchanged GP fees) the costs could be reduced by 26.2% though excluding administrative costs of a new organisation. Conclusion. Substituting GPs with nurses in OOH primary care may increase the cost in fees compared to a model with only GPs. Further research is needed involving more influencing factors, such as costs due to nurse training and running the organisation.


In vivo bioluminescent imaging (BLI): noninvasive visualization and interrogation of biological processes in living animals.
In vivo bioluminescent imaging (BLI) is increasingly being utilized as a method for modern biological research. This process, which involves the noninvasive interrogation of living animals using light emitted from luciferase-expressing bioreporter cells, has been applied to study a wide range of biomolecular functions such as gene function, drug discovery and development, cellular trafficking, protein-protein interactions, and especially tumorigenesis, cancer treatment, and disease progression. This article will review the various bioreporter/biosensor integrations of BLI and discuss how BLI is being applied towards a new visual understanding of biological processes within the living organism.


Overlap and Differences in Migraine and Idiopathic Intracranial Hypertension.
Migraine and idiopathic intracranial hypertension (IIH) are increasingly encountered but remain enigmatic. This review compares the similarities and differences of the diagnostic criteria, pathophysiology, and risk factors for chronic migraine and IIH. While migraine and IIH are distinct diseases, both conditions are frequently found concurrently and may share a link. Increased intracranial pressure (ICP) in those with or without pre-existing migraine may present with migraine-like headaches and contribute to migraine chronification. Increased intracranial pressure may be a coincidental occurrence in patients with migraine and normalization of pressure does not always translate to headache improvement. Limited information is available regarding the standard of treatment for patients with chronic migraine and IIH without papilledema. There continues to be controversy over the normal range of cerebral spinal fluid (CSF) values. Recognizing the concurrence of both conditions advances our understanding of headache pathology and demonstrates a striking need for more research.


Kidney Injury in Critically Ill Patients with COVID-19 - From Pathophysiological Mechanisms to a Personalized Therapeutic Model.
Acute kidney injury is a common complication of COVID-19, frequently fuelled by a complex interplay of factors. These include tubular injury and three primary drivers of cardiocirculatory instability: heart-lung interaction abnormalities, myocardial damage, and disturbances in fluid balance. Further complicating this dynamic, renal vulnerability to a "second-hit" injury, like a SARS-CoV-2 infection, is heightened by advanced age, chronic kidney disease, cardiovascular diseases, and diabetes mellitus. Moreover, the influence of chronic treatment protocols, which may constrain the compensatory intrarenal hemodynamic mechanisms, warrants equal consideration. COVID-19-associated acute kidney injury not only escalates mortality rates but also significantly affects long-term kidney function recovery, particularly in severe instances. Thus, the imperative lies in developing and applying therapeutic strategies capable of warding off acute kidney injury and decelerating the transition into chronic kidney disease after an acute event. This narrative review aims to proffer a flexible diagnostic and therapeutic strategy that recognizes the multi-faceted nature of COVID-19-associated acute kidney injury in critically ill patients and underlines the crucial role of a tailored, overarching hemodynamic and respiratory framework in managing this complex clinical condition.


Predictors of Proximal Interphalangeal Joint Flexion Contracture After Homodigital Island Flap.
To identify independent predictors of postoperative proximal interphalangeal (PIP) joint contracture after direct-flow homodigital island flap transfer. Forty-four fingertip amputations in 39 patients treated with oblique triangular flaps were evaluated at a minimum of 1 year after surgery. Five variables were examined: patient age, injured finger, mechanism of injury, flap advancement distance, and time required for wound healing. Univariate and multivariate linear regression analyses were performed to identify the extent to which these variables affected the flexion contracture of the PIP joint. The average reduction in the passive extension angle of the PIP joint was 16° at final follow-up. Univariate analysis indicated significant correlations of PIP joint flexion contracture with age, injured finger, and time for wound healing, but no significant correlation with the distance the flap was advanced. Multivariate analysis indicated that the age and duration of wound healing were independent predictors of the flexion contracture of the PIP joint. Elderly people and cases with delayed wound healing are at risk for postoperative PIP joint contracture after homodigital flap transfer. Intervention with early hand therapy and orthotics may be useful in elderly patients with delayed wound healing. Prognostic II.


Stimulation of granulopoiesis by high-dose recombinant human granulocyte colony-stimulating factor in children with aplastic anemia and very severe neutropenia.
We investigated the efficacy and safety of high-dose recombinant human granulocyte colony-stimulating factor (rhG-CSF) in treating 10 children with severe aplastic anemia and fewer than 0.05 x 10(9)/L neutrophils. Doses of rhG-CSF ranging from 400 to 2,000 micrograms/m2/d were administered as a 30-minute intravenous infusion daily for 4 weeks. In 6 of the 10 children, treatment increased the neutrophil count by 10-fold to greater than 60-fold (range, 0.21 to 1.8 x 10(9)/L). Bacterial or fungal infections that were present at study entry resolved in all 6 responders, who are still alive with a median survival of more than 27 months (range, 15 to 54 months) since the initiation of treatment. Three of 4 nonresponders died of infection, whereas 1 nonresponder received a bone marrow transplant and is alive. No serious toxicity was attributable to rhG-CSF. It was well tolerated at doses up to 2,000 micrograms/m2/d and effectively stimulated granulopoiesis. This agent thus offers promise as adjuvant treatment for severe infections in children with aplastic anemia and very severe neutropenia.


"I Cry. I Simply Cry." An Ethnography of a Lymphedema Summer Camp.
Background: The aim of this study was to explore how self-management is taught, learnt, and experienced during a 3-day educational Lymphedema Camp for parents of children with lymphedema. Methods: Participants (professionals, parents, and children) were observed during camp activities and interviewed informally and formally in focus groups. The embodied nature of the experience expressed by professionals, parents, and researchers became the analytical focus for understanding the felt tensions in the teaching and learning of self-management to families. Findings: The affective sensibilities associated with the uncertainties involved in teaching and learning self-management skills were palpable given that: young people are now expected to take up strict time-consuming self-management regimens (often via the support of a parent) where "evidence-based" outcomes are uncertain or may not match the outcomes wanted by a young person (varying in age and therefore ability or willingness to engage); or where there are tensions within the family; and the variety of different professionals involved means that techniques varied but where these professionals also lacked the necessary skills training to guide them in how to teach self-management. An analytical focus on the distress, doubt, fear, loneliness, guilt, and moralism felt by professionals, parents, and the researchers supports us to identify the character of the problems associated with performing best practice care guidance where there is a lack of practical support or resources for how self-management in this population should be achieved. Conclusion: To avoid these issues more training and research are needed on "how" to self-manage and stop victim-blaming that generates tensions and drives a wedge between the carer and the cared-for. When systemic problems get located with individuals (professionals, parents, or children), this directs our attention and understanding away from systems of care that lack coordination, may be under-resourced, and where effective training is absent.


Person Re-Identification With Metric Learning Using Privileged Information.
Despite the promising progress made in recent years, person re-identification remains a challenging task due to complex variations in human appearances from different camera views. This paper presents a logistic discriminant metric learning method for this challenging problem. Different with most existing metric learning algorithms, it exploits both original data and auxiliary data during training, which is motivated by the new machine learning paradigm-learning using privileged information. Such privileged information is a kind of auxiliary knowledge, which is only available during training. Our goal is to learn an optimal distance function by constructing a locally adaptive decision rule with the help of privileged information. We jointly learn two distance metrics by minimizing the empirical loss penalizing the difference between the distance in the original space and that in the privileged space. In our setting, the distance in the privileged space functions as a local decision threshold, which guides the decision making in the original space like a teacher. The metric learned from the original space is used to compute the distance between a probe image and a gallery image during testing. In addition, we extend the proposed approach to a multi-view setting which is able to explore the complementation of multiple feature representations. In the multi-view setting, multiple metrics corresponding to different original features are jointly learned, guided by the same privileged information. Besides, an effective iterative optimization scheme is introduced to simultaneously optimize the metrics and the assigned metric weights. Experiment results on several widely-used data sets demonstrate that the proposed approach is superior to global decision threshold-based methods and outperforms most state-of-the-art results.


[Indications for radiotherapy in the superior vena cava syndrome].
The effect of radiotherapy upon the superior vena cava syndrome is studied. The treatment is never curative and the patients survive between 3 and 13 months, but it is useful in 80 per 100 of the cases to alleviate the edema and dyspnea that are always grave.


Gene transcription studies of Candida albicans following infection of HEp2 epithelial cells.
Previously we observed that infection of HEp2 epithelial cells with Candida albicans results in HEp2 cell actin rearrangement as well as reduced membrane ruffling and motility and that supernatants of a C. albicans culture (Candida metabolite) caused the same changes. In this study, we used microarray analysis to determine changes in gene transcription of C. albicans following infection of HEp2 cells compared to control cultures grown in the absence of HEp2 cells. We observed 201 genes whose regulation was increased at least 2-fold following a 3 h incubation with HEp2 cells as well as 87 genes that are down-regulated. Among the up-regulated genes were ALS2 and ALS5 both of which encode proteins that provide an adherence function for C. albicans. To confirm the changes in ALS transcription, we measured by RT-PCR ALS1-9 at 1 h intervals for a total of 4 h. After 1 h of infection, several of the ALS genes were up-regulated compared to C. albicans grown alone. At 2-4 h, an increase in most of the ALS genes was observed in both infected and control cultures. ALS7 transcription was observed only at 3-4 h, but transcription was similar in both infected and control cultures. By RT-PCR, ALS2 and 5, similar to the microarray data, were significantly increased in infected cells at 3 h. Our results show that gene transcription following the adherence of C. albicans to HEp2 cells includes the up-regulation of genes encoding members of a family of known host recognition adhesins that may be critical to successful colonization and invasion of the organism.


[Bipolar disorder: evolution of the concept and current controversies].
The author reviews the evolution of the concept of bipolar disorder as an ongoing process. Its roots can be found in the work of Araeteus of Capadocia, who assumed that melancholia and mania were two forms of the same disease. The modern understanding of bipolar disorder began in France, through the work of Falret (1851) and Baillarger (1854). The pivotal concepts of Emil Kraepelin changed the basis of psychiatric nosology, and Kraepelin's unitary concept of manic-depressive insanity was largely accepted. Kraepelin and Weigandt's ideas on mixed states were the cornerstone of this unitary concept. After Kraepelin, however, the ideas of Kleist and Leonhard, in Germany, as well as the work of Angst, Perris and Winokur, emphasized the distinction between unipolar and bipolar forms of depression. More recently, the emphasis has shifted again to the bipolar spectrum, which, in its mild forms, expanded to the limits of normal temperament. In concluding, the author summarizes the polemic aspects concerning the nosology of bipolar disorder and its boundaries in comparison with those of with schizophrenia, schizoaffective disorders and cycloid psychosis.


Psychological and Physiological Stress in Hens With Bone Damage.
Abnormalities in bone development in humans and non-humans can lead to impaired physical and psychological health; however, evidence is lacking regarding the role of individual psychosocial factors in the development of poor bone conditions. Addressing this lack of knowledge, we used low-productive laying hens (n = 93) and assessed behavioral responses to an open-field test [at 17, 18, 29, 33 weeks of age (wa)], an aerial predator test (at 39 wa), and a social reinstatement test (at 42 wa). Bone condition was assessed using a palpation technique on five occasions (at 16, 29, 33, 45, 58 wa), with half of the hens experiencing damage (deviations, fractures, or both) at 29 wa and all hens by 58 wa. Corticosterone (CORT) concentration in feathers (at 16, 33, 58 wa) and body weight (at 23, 47, 58 wa) were also investigated. We hypothesized that lighter birds (at 23 wa) with higher CORT (at 16 wa) and open field-induced fear collected before the onset of lay (at 17 and 18 wa) are associated with a worse bone condition when in lay. We also hypothesized that those birds with more damage at the peak of laying (at 29 wa) would be lighter at 47 and 58 wa and more fearful by showing higher open field-induced (at 29 and 33 wa) and predator-induced fear responses, however, acting less socially toward conspecifics. These hens were also expected to have higher CORT (at 33 and 58 wa). Our results show no association between open-field fear level and fear behavior, CORT concentration, or body weight on the one hand (all measured before starting to lay) and bone damage at 29 wa on the other. When in lay, bone damage was associated with more pecking and less crossing zones when faced with an open-field situation at 29 wa and improved sociality at 42 wa. This study provides the first evidence of a relationship of bone health with fear, sociality, and stress response. When in poor bone condition, our hens had enhanced psychological stress measured by fear behavior reactivity but not physiological stress measured as feather CORT concentration.


Dose-dependent effects of transcranial alternating current stimulation on spike timing in awake nonhuman primates.
Weak extracellular electric fields can influence spike timing in neural networks. Approaches to noninvasively impose these fields on the brain have high therapeutic potential in neurology and psychiatry. Transcranial alternating current stimulation (TACS) is hypothesized to affect spike timing and cause neural entrainment. However, the conditions under which these effects occur in vivo are unknown. Here, we recorded single-unit activity in the neocortex in awake nonhuman primates during TACS and found dose-dependent neural entrainment to the stimulation waveform. Cluster analysis of changes in interspike intervals identified two main types of neural responses to TACS-increased burstiness and phase entrainment. Our results uncover key mechanisms of TACS and show that the stimulation affects spike timing in the awake primate brain at intensities feasible in humans. Thus, novel TACS protocols tailored to ongoing brain activity may be a tool to normalize spike timing in maladaptive brain networks and neurological disease.


Evidence of learning walks related to scorpion home burrow navigation.
The navigation by chemo-textural familiarity hypothesis (NCFH) suggests that scorpions use their midventral pectines to gather chemical and textural information near their burrows and use this information as they subsequently return home. For NCFH to be viable, animals must somehow acquire home-directed 'tastes' of the substrate, such as through path integration (PI) and/or learning walks. We conducted laboratory behavioral trials using desert grassland scorpions (Paruroctonus utahensis). Animals reliably formed burrows in small mounds of sand we provided in the middle of circular, sand-lined behavioral arenas. We processed overnight infrared video recordings with a MATLAB script that tracked animal movements at 1-2 s intervals. In all, we analyzed the movements of 23 animals, representing nearly 1500 h of video recording. We found that once animals established their home burrows, they immediately made one to several short, looping excursions away from and back to their burrows before walking greater distances. We also observed similar excursions when animals made burrows in level sand in the middle of the arena (i.e. no mound provided). These putative learning walks, together with recently reported PI in scorpions, may provide the crucial home-directed information requisite for NCFH.


A practical and comprehensive immunohistochemical approach to the diagnosis of superficial soft tissue tumors.
Soft tissue tumors include neoplasms of specific and unknown lineages, and, therefore, lineage markers of smooth muscle, skeletal muscle, endothelial, epithelial and Schwann cells have proven useful in everyday practice. However, groups of tumors remain that are defined essentially on grounds of histology; others can be defined by molecular genetic studies. The complex distribution patterns of many antigens and loss of some differentiation antigens in malignant tumors often necessitate the use of panels of antibodies. Optimally such panels should address all significant differential diagnostic alternatives. There is little doubt that numerous new differentiation markers will appear in the future. The evaluation of tumor proliferation, apoptosis, and cell cycle control will give new information related to tumor biology and prognosis.


Rapid identification of thrombocytopenia-associated multiple organ failure using red blood cell parameters and a volume/hemoglobin concentration cytogram.
Thrombocytopenia-associated multiple organ failure (TAMOF) has a high mortality rate when not treated, and early detection of TAMOF is very important diagnostically and therapeutically. We describe herein our experience of early detection of TAMOF, using an automated hematology analyzer. From 498,390 inpatients, we selected 12 patients suspected of having peripheral schistocytosis, based on the results of red blood cell (RBC) parameters and a volume/hemoglobin concentration (V/HC) cytogram. We promptly evaluated whether the individual patients had clinical manifestations and laboratory findings were consistent with TAMOF. Plasma exchanges were then performed for each patient. All 12 patients had TAMOF. The mean values of RBC parameters were significantly higher in all of the patients than with the reference range, however, 3 patients had % RBC fragments within the reference range. The mean value of ADAMTS-13 activity was slightly lower in patients compared with the reference range. Of the 12 patients, remission was obtained in 9 patients (75%) within 4 to 5 weeks using plasma exchanges. Three patients died. An increased percentage of microcytic hyperchromic cells with anisocytosis and anisochromia indicated the presence of schistocytes, making it an excellent screening marker for TAMOF. Identification of TAMOF with RBC parameters and a V/HC cytogram is a facile and rapid method along with an automated hematology analyzer already in use for routine complete blood cell counting test.


Association Between Improvement in Baseline Mood and Long-Term Use of a Mindfulness and Meditation App: Observational Study.
The use of smartphone apps to monitor and deliver health care guidance and interventions has received considerable attention recently, particularly with regard to behavioral disorders, stress relief, negative emotional state, and poor mood in general. Unfortunately, there is little research investigating the long-term and repeated effects of apps meant to impact mood and emotional state. We aimed to investigate the effects of both immediate point-of-intervention and long-term use (ie, at least 10 engagements) of a guided meditation and mindfulness smartphone app on users' emotional states. Data were collected from users of a mobile phone app developed by the company Stop, Breathe & Think (SBT) for achieving emotional wellness. To explore the long-term effects, we assessed changes in the users' basal emotional state before they completed an activity (eg, a guided meditation). We also assessed the immediate effects of the app on users' emotional states from preactivity to postactivity. The SBT app collects information on the emotional state of the user before and after engagement in one or several mediation and mindfulness activities. These activities are recommended and provided by the app based on user input. We considered data on over 120,000 users of the app who collectively engaged in over 5.5 million sessions with the app during an approximate 2-year period. We focused our analysis on users who had at least 10 engagements with the app over an average of 6 months. We explored the changes in the emotional well-being of individuals with different emotional states at the time of their initial engagement with the app using mixed-effects models. In the process, we compared 2 different methods of classifying emotional states: (1) an expert-defined a priori mood classification and (2) an empirically driven cluster-based classification. We found that among long-term users of the app, there was an association between the length of use and a positive change in basal emotional state (4% positive mood increase on a 2-point scale every 10 sessions). We also found that individuals who were anxious or depressed tended to have a favorable long-term emotional transition (eg, from a sad emotional state to a happier emotional state) after using the app for an extended period (the odds ratio for achieving a positive emotional state was 3.2 and 6.2 for anxious and depressed individuals, respectively, compared with users with fewer sessions). Our analyses provide evidence for an association between both immediate and long-term use of an app providing guided meditations and improvements in the emotional state.


Acute pseudomonas mastoiditis in children.
Five children with acute pseudomonas mastoiditis were treated and followed up in our medical center during a period of three years. The main clinical features of the disease include predilection for young male infants, a high rate of local aggressiveness, prolonged hospitalization for repeated surgical procedures, and the need for several courses of intravenous specific antimicrobial therapy. Although correctly diagnosed and promptly treated, these patients may be destined to chronic ear disorders.


Dietary interventions for functional abdominal pain disorders in children: a systematic review and meta-analysis.
Functional abdominal pain disorders (FAPDs) are common among children and are associated with decreased quality of life and school attendance. Several dietary interventions have been suggested to improve symptoms of FAPDs. This systematic review assessed the efficacy and safety of dietary interventions for pediatric FAPDs. Electronic databases were searched (inception-October 2021). Systematic reviews or RCTs were included if children (4-18 years) with FAPDs were treated with dietary interventions and compared to placebo, no diet or any other diet. Data extraction and assessment of quality of evidence based on GRADE system was independently performed by two review authors. Outcomes were treatment success, pain intensity and frequency, and withdrawal due to adverse events. Twelve articles were included, representing data of 819 pediatric FAPD patients. Trials investigating fibers, FODMAP diet, fructans, fructose-restricted diet, prebiotic (inulin), serum-derived bovine immunoglobulin, and vitamin D supplementation were included. We found very low-certainty evidence that the use of fibers leads to higher treatment success (NNT = 5). Based on current evidence, the use of fibers can be discussed in daily practice. High-quality intervention trials are highly needed to investigate if other dietary interventions are effective in the treatment of pediatric FAPD.


Cellular and molecular mechanisms involved in the establishment of HIV-1 latency.
Latently infected cells represent the major barrier to either a sterilizing or a functional HIV-1 cure. Multiple approaches to reactivation and depletion of the latent reservoir have been attempted clinically, but full depletion of this compartment remains a long-term goal. Compared to the mechanisms involved in the maintenance of HIV-1 latency and the pathways leading to viral reactivation, less is known about the establishment of latent infection. This review focuses on how HIV-1 latency is established at the cellular and molecular levels. We first discuss how latent infection can be established following infection of an activated CD4 T-cell that undergoes a transition to a resting memory state and also how direct infection of a resting CD4 T-cell can lead to latency. Various animal, primary cell, and cell line models also provide insights into this process and are discussed with respect to the routes of infection that result in latency. A number of molecular mechanisms that are active at both transcriptional and post-transcriptional levels have been associated with HIV-1 latency. Many, but not all of these, help to drive the establishment of latent infection, and we review the evidence in favor of or against each mechanism specifically with regard to the establishment of latency. We also discuss the role of immediate silent integration of viral DNA versus silencing of initially active infections. Finally, we discuss potential approaches aimed at limiting the establishment of latent infection.


Implementation strategy for introducing a clinical skills examination to the Korean Oriental Medicine Licensing Examination: a mixed-method modified Delphi study
This study investigated the validity of introducing a clinical skills examination (CSE) to the Korean Oriental Medicine Licensing Examination through a mixed-method modified Delphi study A 3-round Delphi study was conducted between September and November 2022. The expert panel comprised 21 oriental medicine education experts who were officially recommended by relevant institutions and organizations. The questionnaires included potential content for the CSE and a detailed implementation strategy. Subcommittees were formed to discuss concerns around the introduction of the CSE, which were collected as open-ended questions. In this study, a 66.7% or greater agreement rate was defined as achieving a consensus. The expert panel's evaluation of the proposed clinical presentations and basic clinical skills suggested their priorities. Of the 10 items investigated for building a detailed implementation strategy for the introduction of the CSE to the Korean Oriental Medicine Licensing Examination, a consensus was achieved on 9. However, the agreement rate on the timing of the introduction of the CSE was low. Concerns around 4 clinical topics were discussed in the subcommittees, and potential solutions were proposed. This study offers preliminary data and raises some concerns that can be used as a reference while discussing the introduction of the CSE to the Korean Oriental Medicine Licensing Examination.


Proposed treatment strategy for cavernous sinus meningiomas: a prospective study.
To establish a safe and effective treatment strategy for cavernous sinus (CS) meningiomas, we prospectively analyzed the outcome of a treatment protocol combining surgery and radiosurgery during the past 7 years. Tumors confined to the CS and distant from the optic apparatus and the brainstem were treated with radiosurgery alone. Tumors attached to or compressing the optic apparatus and brainstem and that were larger than 3 cm in mean diameter, extended into the multiple cranial fossae, and were suspected of being malignant were treated with combined nonradical microsurgery and radiosurgery. In accordance with this treatment protocol, 40 patients aged 26 to 72 years (median, 51 yr) with primary (n = 27) or recurrent (n = 13) CS meningiomas (volume range, 0.9-39.3 cm(3); median volume, 5.4 cm(3)) were treated with combined surgery and radiosurgery (n = 23) or radiosurgery alone (n = 17). During radiosurgery, 12 to 18 Gy (median, 16 Gy) was delivered to the tumor margin. The follow-up period ranged from 14 to 79 months (median, 47 mo). The actuarial tumor control rate was 94.1% at 5 years. The improvement of cranial nerve function was significantly frequent in patients with primary CS meningiomas (P < 0.05). Permanent cranial nerve dysfunction was significantly frequent in patients with tumors compressing the brainstem or smaller than 10 cm(3) (P < 0.05). All 36 patients with a pretreatment Karnofsky Performance Scale score of 90 or more maintained the same range after treatment. Proper combination of microsurgery and radiosurgery for CS meningiomas provides excellent growth control with favorable functional state. Outcomes were better when this protocol was adopted at the initial diagnosis for patients with smaller tumors that did not compress the brainstem.


Temperature, not LuxS, mediates AI-2 formation in hydrothermal habitats.
Quorum sensing provides the basis for coordinating community-wide, microbial behaviors in many mesophilic bacteria. However, little attention has been directed toward the possibility that such phenomena occur in extremely thermal microbial environments. Despite the absence of luxS in hyperthermophile genomes, autoinducer-2 (AI-2), a boronated furanone and proposed 'universal' interspecies mesophilic bacterial communication signal, could be formed by Thermotoga maritima and Pyrococcus furiosus through a combination of biotic and abiotic reaction steps. AI-2 did not, however, induce any detectable quorum-sensing phenotypes in these organisms, although transcriptome-based evidence of an AI-2-induced stress response was observed in T. maritima. The significance, if any, of AI-2 in hydrothermal habitats is not yet clear. Nevertheless, these results show the importance of considering environmental factors, in this case high temperatures, as abiotic causative agents of biochemical and microbiological phenomena.


The treatment of locally advanced head and neck cancer with misonidazole, hyperbaric oxygen and irradiation: an interim report.
Thirty-one patients with advanced inoperable squamous carcinoma of the mouth were treated in a pilot study with misonidazole (2.0 gm/m2) with each of six fractions of 6.0 Gy in hyperbaric oxygen at 3 ATA. The one and two year disease free survival was 48 and 26%, respectively. A prospective randomized trial is now being conducted comparing this regimen with 63.0 Gy in 30 fractions in 38 days in air. One hundred-fourteen patients have been entered; 91 are available for analysis at six months or more. The preliminary results at 6 and 12 months favor the combination of sensitizers. There is no added toxicity.


Percutaneous dilational tracheostomy technique and experience.
A technique for percutaneous insertion of an adult tracheostomy tube in the Intensive Care Unit is described. Experience with twenty-one insertions over an eight-month period is reviewed. No major complication was noted at insertion, during cannulation or after removal in any patient. We have found the percutaneous dilational technique to be an effective and safe procedure which can be used routinely for elective tracheostomy in intubated adult patients.


Substance use and sexual risk behavior in HIV-positive men who have sex with men: an episode-level analysis.
Men who have sex with men (MSM) make up nearly half of all people living with HIV in the United States. The prevalence of the epidemic in this population makes it vitally important to understand the transmission of the infection and to develop methods to prevent its spread. The current study uses longitudinal diary methods to examine relationships between substance use and unprotected anal intercourse in a sample of 158 HIV-positive, mostly ethnic minority MSM. Results indicate that both general substance use and use of specific drugs (i.e., inhalants, cocaine, crack, and club drugs) have a substantial impact on the sexual risk behavior of this population.


Mouse VH7183 recombination signal sequences mediate recombination more frequently than those of VHJ558.
Mouse VH gene segments are conventionally classified into 13 families on the basis of sequence similarity. The 7183 family lies close to the 3' end of the locus and is preferentially used in BALB/c mice; J558, the largest family, lies close to the 5' end of the VH stretch and is preferentially used in C57BL/6 mice. To investigate whether differential effectiveness of the RSSs in the two families might contribute to the overusage of 7183 in the primary repertoire of BALB/c, we constructed recombination substrates in which the recombination signal sequences (RSSs) of VH segments 7183 and J558 compete with each other for a single RSS, DFL16.1, after transfection into two transformed cell lines derived from C57BL/6 and two cell lines from BALB/c mice. In both strains, the 7183 RSS was found to be preferentially used (83%). Thus, the 7183 RSS mediates recombination more frequently than does that of J558, and this preference must thereby influence the primary repertoire, but the strain difference cannot be accounted for by a difference in the RSSs.


Formulation strategies for drug delivery of tacrolimus: An overview.
Tacrolimus (FK 506) is a potent macrolide lactone immunosuppressive agent used for prophylaxis of organ rejection after transplantation and graft-versus-host disease after bone marrow transplantation in patients. Moreover, tacrolimus is a drug of choice in the treatment of atopic dermatitis for decreasing side effects associated with the use of topical corticosteroids. In spite of its success in ensuring graft survival, therapeutic use of tacrolimus is complicated due to its narrow therapeutic index (between 5 and 15 ng/ml). Tacrolimus has a large inter-/intra-patient variability in pharmacokinetics profile and a poor oral bioavailability because of its poor solubility, P-gp efflux, marked pre-systemic metabolism by CYP3A in the enterocytes and liver first pass effect. Several formulation approaches such as oily solution, solid dispersions, complexation with cyclodextrins, liposomes etc., have been investigated to improve oral delivery of FK 506. In this review, we have discussed various formulation approaches that have been undertaken by various researchers to solve the problems related to the drug delivery of tacrolimus.


Dormitory of Physical and Engineering Sciences: Sleeping Beauties May Be Sleeping Innovations.
A 'Sleeping Beauty in Science' is a publication that goes unnoticed ('sleeps') for a long time and then, almost suddenly, attracts a lot of attention ('is awakened by a prince'). The aim of this paper is to present a general methodology to investigate (1) important properties of Sleeping Beauties such as the time-dependent distribution, author characteristics, journals and fields, and (2) the cognitive environment of Sleeping Beauties. We are particularly interested to find out to what extent Sleeping Beauties are application-oriented and thus are potential Sleeping Innovations. In this study we focus primarily on physics (including materials science and astrophysics) and present first results for chemistry and for engineering & computer science. We find that more than half of the SBs are application-oriented. To study the cognitive environments of Sleeping Beauties we develop a new approach in which the cognitive environment of the SBs is analyzed, based on the mapping of Sleeping Beauties using their citation links and conceptual relations, particularly co-citation mapping. In this way we investigate the research themes in which the SBs are 'used' and possible causes of why the premature work in the SBs becomes topical, i.e., the trigger of the awakening of the SBs. This approach is tested with a blue skies SB and an application-oriented SB. We think that the mapping procedures discussed in this paper are not only important for bibliometric analyses. They also provide researchers with useful, interactive tools to discover both relevant older work as well as new developments, for instance in themes related to Sleeping Beauties that are also Sleeping Innovations.


European Heart Rhythm Association Summit report 2014.
Across Europe, the role of the welfare state is constantly being questioned and even eroded. At the same time, funding sources for post-graduate medical education and training are under attack as regulators review the working relationships between physicians and industry. Both of these issues have profound consequences for cardiologists and their patients, and were, therefore, chosen as the themes of the European Heart Rhythm Association (EHRA) 2014 Spring Summit held at Heart House, Sophia Antipolis, 25-26 March 2014. The meeting noted that some of the changes are already affecting patient care standards and that this is exacerbated by a reduction in research and education programmes. The principle conclusion was that EHRA must find better means of engagement with the authorities across Europe to ensure that its views are considered and that ethical patient care is preserved. Participants were particularly alarmed by the example from Sweden in which future healthcare planning appears to exclude the views of physicians, although this is not yet the case in other countries. The demand for greater transparency in relationships between physicians and industry was also discussed. Although intended to eliminate corruption, concern was expressed that such moves would cause long-term damage to education and research, threatening the future of congresses, whose role in these areas appears underestimated by the authorities.


Embrained drives to perform extraordinary roles predict schizotypal traits in the general population.
Some personal drives correspond to extraordinary social roles. Given that behavioral strategies associated with such drives may conflict with those associated with ordinary roles, they could cause behavioral disorganization. To test whether they do so independent of the factors responsible for full-blown schizotypy and schizophrenia, these drives were assessed in the general population. Two hundred and nine healthy volunteers were individually presented with hundreds of names of social roles in experimental psychology conditions. The task of the participant was to decide whether or not (s)he would consider performing the role at any moment of his/her life. Schizotypal traits were measured with the schizotypal personality questionnaire (SPQ), and delusion-like ideations were assessed by the Peters et al. Delusion Inventory. Demographics and social desirability were controlled for. Participants accepting a greater percentage of extraordinary roles had higher SPQ scores. Among the three factors of the SPQ, disorganization was the one best predicted by those percentages. This correlation (r=0.40, P=7.2E-09) was significantly greater (Fisher Z-transform, P=0.003) than the correlation between the percentages of ordinary roles accepted and the SPQ scores (r=0.145, P=0.044). Reaction times revealed no suboptimal cognitive functioning in high accepters of extraordinary roles and further strengthened the drive hypothesis. Their acceptances of roles were done faster and their rejections took longer than those of low accepters (P=5E-12). Culturally embrained drives to do extraordinary roles could thus be an independent factor of the symptoms measured in the normality to schizophrenia continuum.


Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer.
Colorectal cancer (CRC) is one of the most common and recurrent types of cancer, with high mortality rates. Several clinical trials and meta-analyses have determined that the use of pharmacological inhibitors of cyclooxygenase 2 (COX-2), the enzyme that catalyses the rate-limiting step in the synthesis of prostaglandins (PG) from arachidonic acid, can reduce the incidence of CRC as well as the risk of recurrence of this disease, when used together with commonly used chemotherapeutic agents. These observations suggest that inhibition of COX-2 may be useful in the treatment of CRC, although the current drugs targeting COX-2 are not widely used since they increase the risk of health complications. To overcome this difficulty, a possibility is to identify genes regulated by COX-2 activity that could give an advantage to the cells to form tumors and/or metastasize. The modulation of those genes as effectors of COX-2 may cancel the beneficial effects of COX-2 in tumor transformation and metastasis. A review of the available databases and literature and our own data have identified some interesting molecules induced by prostaglandins or COX-2 that have been also described to play a role in colon cancer, being thus potential pharmacological targets in colon cancer. Among those mPGES-1, DUSP4, and 10, Programmed cell death 4, Trop2, and many from the TGFβ and p53 pathways have been identified as genes upregulated in response to COX-2 overexpression or PGs in colon carcinoma lines and overexpressed in colon tumor tissue. Here, we review the available evidence of the potential roles of those molecules in colon cancer in the context of PG/COX signaling pathways that could be critical mediators of some of the tumor growth and metastasis advantage induced by COX-2. At the end, this may allow defining new therapeutic targets/drugs against CRC that could act specifically against tumor cells and would be effective in the prevention and treatment of CRC, lacking the unwanted side effects of COX-2 pharmacological inhibitors, providing alternative approaches in colon cancer.


Selection between pinching-type and supramolecular polymer-type complexes by alpha-cyclodextrin-beta-cyclodextrin hetero-dimer and hetero-cinnamamide guest dimers.
Novel supramolecular complexes have been prepared from an alpha-cyclodextrin-beta-cyclodextrin hetero-dimer (alpha-CD-beta-CD hetero-dimer) and hetero-cinnamamide guest dimers, G-t-Boc and G-NH2, having adamantyl groups in aqueous solutions. On addition of the competitive guest, the supramolecular structure formed by a mixture of the alpha-CD-beta-CD hetero-dimer and G-t-Boc was found to be different from that of a mixture of the alpha-CD-beta-CD hetero-dimer and G-NH2 by the 1H NMR spectroscopy, the ROESY NMR spectroscopy, and the circular dichroism spectroscopy. The size of the supramolecular complex from the mixture of the alpha-CD-beta-CD hetero-dimer and G-NH2 is larger than that from the mixture of the alpha-CD-beta-CD hetero-dimer and G-t-Boc, which was proved by the pulse field gradient spin-echo NMR and the atomic force microscopy. These results suggest that the mixture of the alpha-CD-beta-CD hetero-dimer and G-t-Boc formed a pinching-type complex, and the mixture of the alpha-CD-beta-CD hetero-dimer and G-NH2 formed a supramolecular polymer-type complex.


Patients' attitudes toward electronic health information exchange: qualitative study.
In many countries, there has been substantial progress in establishing the electronic transmission of patients' health information between health care providers, but little is known about how best to engage patients in the process. We explored patients' views about sharing of electronic health information and their preferences for learning about and participating in this process. Patients in one Massachusetts community in the northeastern United States were recruited to participate in focus-group discussions. Prior to discussion, participants completed a written questionnaire that captured their reactions to draft educational materials and a consent form. The discussion moderator and two physicians analyzed the moderator's detailed notes from each session and participants' written comments, using an immersion-crystallization approach. Three dominant themes emerged: (1) concerns about privacy and security, (2) the potential benefit to a person's health, and (3) the desire for more information about the consent process. On the pre-discussion questionnaire, 55 out of 62 participants (88%) indicated that they would provide consent for their information to be shared electronically among their health care providers, given the materials they had reviewed. Patients are enthusiastic about electronic health information exchange, recognizing its capacity to improve the quality and safety of health care; however, they are also concerned about its potential to result in breached privacy and misuse of health data. As the exchange of electronic health information becomes more widespread, policy makers will need to ensure that patients have access to concise educational materials and opportunities to engage in conversations about the risks and benefits of participation.


A comparative analysis of novel fluorescent proteins as reporters for gene transfer studies.
We evaluated novel fluorescent proteins (FPs) as reporters for gene transfer in animals and cells with the aim to develop more-sensitive assays for vector development and the optimization of gene transfer strategies in gene therapy. Adeno-associated virus serotype 5 vectors carrying an expression cassette with a chicken beta-actin promoter encoding the green FPs ZsGreen1, AcGFP1, hMGFP (with and without intron), and EGFP and the red FPs DsRed2 and TurboRFP were administered to mice at identical doses for each organ to target liver, lung, and muscle. Despite the fact that all FPs were expressed from an identical vector backbone, the observed number of fluorescent cells and fluorescence intensities varied between, but was consistent within, each combination of a specific protein and organ. The highest number of fluorescent cells was observed in liver with EGFP and in lung with ZsGreen1 and EGFP. In muscle, AcGFP1 and ZsGreen1 produced the most-intense fluorescence in fibers. In contrast, in culture cells, ZsGreen1 showed substantially stronger fluorescence than all other proteins. Our data demonstrate that each FP has tissue-specific expression profiles that need to be taken into consideration when comparing the performance of vectors in different organs.


Simian retrovirus serogroup 2 constitutive transport element recognizes the ribosomal L10-like protein and translocon gamma subunit-like protein in a yeast three-hybrid assay.
The simian retrovirus (SRV) serogroup 2 genome contains a constitutive transport element (CTE) within its 3' intergenic region (IR) that mediates the nuclear export of unspliced SRV RNA. In a previous report [Virology 264 (1999) 37], CTE RNA-protein complexes were detected using UV-crosslinking/sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). To identify these CTE-interacting cellular proteins, we utilized yeast three-hybrid interaction approaches using the complete IR as bait, modified to eliminate transcriptional termination signals recognized by RNA polymerase III, and identified several interactive clones from a Hela cell cDNA activation domain (AD) library. UV-crosslinking of RNA-protein complexes, using Hela cell extracts and the modified IR bait, were conducted prior to library screening, to verify appropriate interaction of CTE RNA-protein complexes. Over one million recombinants were screened, and our yeast hybrid results indicate that the CTE interacts with several molecules involved in cellular translational and translocation machinery, including the ribosomal L10-like protein and the tranlocon protein gamma subunit-like protein. UV-crosslinking/immunoblot assays have verified the interaction of the CTE region with molecules immunologically reactive to antibodies recognizing the ribosomal L10-like protein.


[Nucleotide sequence of cDNA of glicinin A3 subunits: variability of different species detected by comparative analysis].
Several cDNA cloned which code for subfamily A3 subunits (A3B4 and A5A4B3) of soybean storage protein glycinin were analysed by means of restriction mapping and hybrid - selection. The comparison of A3B4 and A5A4B3 subunits cDNA sequences reveals the 90% homology. The nucleotide sequences obtained in the process of this work were compared with those reported about elsewhere, in order to study the interaspecific variability of homologous but not identical storage protein genes of subfamily A3 glycinin subunit. Nucleotide replacements were found to occur 6 times more frequently in A3B4 subunit gene, as compared to A5A4B3 subunit gene (48 replacements against 8).


Preoperative injection of carbon nanoparticles is beneficial to the patients with thyroid papillary carcinoma: From a prospective study of 102 cases.
More surgeons had noticed the importance of carbon nanoparticles (CNs) in protection of parathyroid grand in the surgery of thyroidectomy and central lymph lode dissection, but paid less attention to the injection time. The purpose of this study was to investigate whether preoperative injection of CNs can improve the dissection of lymph nodes (LNs) and protect parathyroid grand (PG) for the patients with papillary thyroid carcinoma (TC). A total of 102 consecutive patients were enrolled into this study from August 2016 to June 2017. All the patients were divided randomly into preoperative group and intraoperative group by the injecting time of the CNs. We compared the patients who had CNs injected into thyroid gland 1 month before surgery with a control group of patients who had CNs injected during the operation. The primary endpoints were operative time, numbers of total LN and metastatic LN, ratio of PG auto-transplantation, parathyroid hormone (PTH) level, and postoperative complications. We identify 206 PGs and 162 PGs in the preoperative and intraoperative group, respectively, (P = .000) and there was low ratio of auto-transplantation in the preoperative group compared with the intraoperative group (39.3% vs 50.62%, P = .003). We also found that the PTH level in the preoperative group was higher than that of preoperative group (2.60 ± 1.00 vs 2.19 ± 0.72, P = .021), and the operation time in the preoperative group was less than the intraoperative group (60.17 ± 6.28 vs 80.94 ± 7.12, P = .000). Meanwhile pathological results revealed 3 PGs of accidental removal occurred in the preoperative group, whereas 9 PGs of accidental removal occurred in the intraoperative group (P = .039). Also there was no difference in the numbers of total and metastatic LN in the 2 groups (P > .05). Preoperative injection of CNs was safe, and can help protect PG and reduce the difficulty of operation.


Wegener's granulomatosis: a challenging disease for otorhinolaryngologists.
Diagnosis of Wegener's granulomatosis (WG) can be delayed because of its aspecific presenting symptoms. Detection of serum circulating antineutrophil cytoplasm antibodies (c-ANCAs), in combination with histology, permits one to identify WG at an early stage and to implement stage-adapted therapy. c-ANCA levels may also help to evaluate the response to medical therapy. Recently, the quality of life of WG patients has been improved by administering cotrimoxazole in order to prevent infections and recurrent diseases during the remission period.WG is of special significance to the otorhinolaryngologist because it is often initially limited to the upper respiratory tract before becoming systemic. The aim of this paper was to describe a series of WG patients and underline the difficulties involved in diagnosing and treating this challenging disease. This was a prospective study in 23 consecutive patients with head and neck manifestations of WG (17 systemic, 6 limited). Diagnosis was performed by means of both c-ANCAs detection using indirect immunofluorescence and histology in biopsy specimens. Treatment consisted of daily cyclophosphamide (CYC; 2 mg/kg/day) and glucocorticoids (prednisone; 1 mg/kg/day). If an improvement or toxic events occurred, CYC was discontinued and methotrexate was started. If, during remission of the disease, low serum c-ANCAs levels were detected, CYC was suspended and cotrimoxazole (1 g/day) was introduced. Serum c-ANCAs detection was positive for all patients. Biopsy was diagnostic from the beginning in 19/23 cases. The six patients with limited WG did not show a progression to systemic disease. Only 3 patients with a diagnosis of delayed systemic WG died, whereas 19/23 patients were alive with good control of relapses.


Distribution of Initiation Times Reveals Mechanisms of Transcriptional Regulation in Single Cells.
Transcription is the dominant point of control of gene expression. Biochemical studies have revealed key molecular components of transcription and their interactions, but the dynamics of transcription initiation in cells is still poorly understood. This state of affairs is being remedied with experiments that observe transcriptional dynamics in single cells using fluorescent reporters. Quantitative information about transcription initiation dynamics can also be extracted from experiments that use electron micrographs of RNA polymerases caught in the act of transcribing a gene (Miller spreads). Inspired by these data, we analyze a general stochastic model of transcription initiation and elongation and compute the distribution of transcription initiation times. We show that different mechanisms of initiation leave distinct signatures in the distribution of initiation times that can be compared to experiments. We analyze published data from micrographs of RNA polymerases transcribing ribosomal RNA genes in Escherichia coli and compare the observed distributions of interpolymerase distances with the predictions from previously hypothesized mechanisms for the regulation of these genes. Our analysis demonstrates the potential of measuring the distribution of time intervals between initiation events as a probe for dissecting mechanisms of transcription initiation in live cells.


Globus Symptoms in Patients Undergoing Thyroidectomy: Relationships with Psychogenic Factors, Thyroid Disease, and Surgical Procedure.
The number of patients who need thyroid surgery has increased worldwide in recent decades. Patients with thyroid disease experience globus pharyngeus as a result of direct compression and edema of the surrounding organs. Thyroid surgery is needed to improve these symptoms or as treatment for thyroid cancer. After thyroid surgery, globus symptoms may become worse and may affect the daily life of the patient for a long time. Psychogenic problems have also been thought to cause the globus sensation. A prospective analysis of globus symptoms and psychogenic factors following thyroidectomy was performed. Patients scheduled to undergo thyroid surgery between February and September 2016 completed the foreign-body sensation in the throat score (FBST; range 0-8.2) and the self-rating depression scale (SDS; range 0-100) preoperatively and three days, one month, three months, six months, and 12 months postoperatively. Long-term follow-up was completed in 616 patients (491 females). A total of 365 patients had thyroid cancer, 169 had benign tumors, and 82 had diffuse goiters with Graves' disease. The percentage of patients who complained about neck discomfort (FBST >2) was 29.4% before surgery. A preoperative high FBST showed a significant direct correlation with a high SDS, but thyroid volume did not. A postoperative high FBST was seen in 75.3% of patients at two days and 78.9% at one month after surgery, and it then gradually decreased to 49.3% at 12 months after surgery. At three days after the operation, the median FBST was significantly higher in patients who had total thyroidectomy with lateral neck dissection or total thyroidectomy only compared to those who had lobectomy only (p < 0.05). These differences were still present 12 months after surgery. A higher preoperative SDS score was also identified as an independent predictor for a high FBST at 12 months after surgery, but not at one or three months postoperatively, on multivariate analyses. Preoperative globus symptoms appear directly related to psychological factors. The area of the surgical procedure and preoperative psychological factors were related to persistent neck discomfort.


Stem cell research in Brazil: the production of a new field of science.
Based on a review of the literature published in the early twenty-first century by Brazilian researchers, the article offers an overview of stem cell research in Brazil. Three central topics were detected in these papers: (1) the funding of stem cell research in Brazil; (2) preclinical and clinical trials in Brazil; and (3) social anthropological analysis focused on ethical and legal matters. Our review identifies controversial questions in the construction of this scientific field, especially issues involving the media as a disseminator of values and of certain social representations, where new kinds of hope figure large. Within this climate of uncertainty, we find patients and their families energized by the promises of the "medicine of the future."


Effect of static stretching of quadriceps and hamstring muscles on knee joint position sense.
To evaluate if a stretch regimen consisting of three 30 second stretches would alter joint position sense (JPS). A blinded, randomised, cross over design with a washout time of 24 hours was used with 20 healthy volunteers. JPS was estimated from the ability to reproduce the same position in one knee (target versus estimated angle) expressed as the difference between target and estimated angle (constant error, CE). Measurements were repeated three times in a sitting and a prone position on the dominant leg measured before and immediately after the static stretch. The static stretch consisted of a 30 second stretch followed by a 30 second pause, repeated three times. At baseline, the mean (SD) CE was -2.71 (3.57) degrees in the sitting position. No difference (p = 0.99) in CE between stretching and control was observed (0.00; 95% confidence interval -0.98 to 0.99). At baseline, the CE was -3.28 (4.81) degrees in the prone position. No difference (p = 0.89) in CE between stretching and control was observed (0.12; 95% confidence interval -1.52 to 1.76). A static stretch regimen had no effect on JPS in healthy volunteers.


Relationship Between Pneumonia and Dysphagia in Patients With Multiple System Atrophy.
Dysphagia is one of the most clinically significant disabilities in patients with multiple system atrophy (MSA), because it can cause aspiration pneumonia, which is potentially fatal. In this study, the Neuromuscular disease Swallowing Status Scale (NdSSS), which was developed to evaluate dysphagia in patients with neuromuscular diseases, was used to evaluate patients with MSA. In addition, correlation between a history of pneumonia and swallowing function was evaluated. Study 1: Reliability, concurrent validity, and responsiveness of the NdSSS in patients with MSA. In 81 patients for whom evaluation items could be collected, the NdSSS was tested for its interrater and intrarater reliability using weighted kappa statistics. Concurrent validity was assessed by correlating the NdSSS with existing scales (Functional Oral Intake Scale (FOIS), Functional Intake LEVEL Scale (FILS), and the unified MSA rating scale (UMSARS)) using Spearman's rank correlation coefficients. Sixty-three patients were evaluated by videofluorographic (VF) swallowing examination. To evaluate concurrent validity, Spearman's rank correlation coefficients were calculated between the NdSSS and VF swallowing assessments. Additionally, scale responsiveness was determined using the standardized response mean (SRM) in 23 patients who could be followed up to assess their long-term course. Study 2: Cross-sectional survey of swallowing function and history of pneumonia. Data regarding history of pneumonia, UMSARS, NdSSS, age, sex, MSA subtype, and disease duration were retrospectively obtained from the medical records of 113 patients with MSA. Differences in these parameters and NdSSS stage between those with and without a history of pneumonia were examined using the Mann-Whitney test or chi-squared test. Furthermore, clinical factors related to a history of pneumonia were examined by binomial logistic regression analysis. The NdSSS showed satisfactory reliability, concurrent validity, and responsiveness. A history of pneumonia was related to the severity of MSA, age, MSA subtype, and NdSSS stage. Binomial logistic regression analysis showed that NdSSS stage (odds ratio (OR), 0.490; 95% confidence interval (CI), 0.301-0.797, p = 0.001) and MSA subtype (OR, 4.031; 95% CI, 1.225-13.269, p = 0.021) were significantly associated with a history of pneumonia. In patients with MSA, the NdSSS has sufficient reliability, concurrent validity, and responsiveness for assessing dysphagia. Patients with a history of pneumonia have more severe dysphagia. We found that the pneumonia risk was related to NdSSS stage and MSA-p (predominantly parkinsonism). Meticulous care to prevent aspiration is needed from early stages of the disease.


Challenges in luting fibre posts: Adhesion to the post and to the dentine.
To investigate the relationship between physicochemical interactions of resin luting cements with dentine and retention of fibre posts in root canals. Retention of fibre posts (RelyX Fiber Post) was assessed by the pull-out method. The diffusion zone of the cements and their chemical interaction with dentine were estimated by micro-Raman spectroscopy. Resin luting cements employing etch-and-rinse (Rely X Ultimate and Variolink II), self-etch (Rely X Ultimate and Panavia F2.0), or self-adhesive (RelyX Unicem 2) modes were investigated. Data were analyzed by analysis of variance followed by Tukey HSD tests. The retention of the fibre posts decreased in the following order: RelyX Ultimate, etch-and-rinse mode>RelyX Unicem 2≥RelyX Ultimate, self-etch mode≥Panavia F2.0≥Variolink II (p<0.05). One of the etch-and-rinse mode cements presented the deepest diffusion zone, while the other, along with the self-adhesive cement, produced the shallowest zone. Cements used in the self-etch mode showed intermediary diffusion into dentine (p<0.05). All resin luting cements showed some degree of chemical interaction with dentine, the highest recorded for RelyX Ultimate used in the etch-and-rinse mode and the lowest for Panavia F2.0 (p<0.05). The retention of fibre posts in the root canal could be attributed neither to the mode of interaction of the luting cements with dentine nor to their ability to diffuse into dentine. Chemical interaction between the resin luting cement and the dentine paired with adequate post pretreatment contribute positively to the retention of fibre posts.