Considerations of germline testing in prostate cancer screening.
Prostate cancer screening remains controversial in the medical field. While screening men above 50 years can impose overdiagnosis and overtreatment, targeted screening of males with pathologic variants of genetic mutations is evolving and viewed as sensible. Identifying such patients requires genetic testing in males having family history of prostate cancer or certain ethnicity. Such strategies will likely occur as routine practice once favorable results of ongoing studies assessing genetic predisposition are released.


Mg/Ca Thermometry in Coral Skeletons
The magnesium-to-calcium (Mg/Ca) ratio of coral skeletons from Ishigaki Island, Ryukyu Islands, Japan, closely tracked sea surface temperature (SST) over an 8-year period. Measurements were made with the fast technique of inductively coupled plasma-atomic emission spectrometry. The variation of the coral Mg/Ca ratio with SST change is about four times that of the current, widely used coral strontium-to-calcium ratio. The temporal and geographic variation of the seawater Mg2+/Ca2+ ratio probably has little influence on coral Mg/Ca variation. Results indicate that the coral Mg/Ca ratio has the potential to provide fast, precise, high-resolution proxies for past tropical SSTs.


Perceptions of good medical practice in the NHS: a survey of senior health professionals.
To categorize senior health professionals' experience with poor medical practice in hospitals and in general practice, to describe perceptions which senior NHS staff have of good medical practice, and to describe how problems of poor medical practice are currently managed. A postal questionnaire survey. The questionnaire sought perceptions of good medical practice, asked participants to characterise deviations from good practice, and to describe experience with managing poor performance at the time of the introduction of the General Medical Council (GMC) performance procedures. A range of NHS settings in the UK: hospital trusts, health authorities/boards, local medical committees, community health councils. Senior health professionals involved in the management of medical professional performance. Perceptions of what constitutes good medical practice. Most respondents considered that persistent problems related to clinical practice (diagnosis, management, and outcome and prescribing) would require local management and, possibly, referral to the GMC performance procedures. Informal mechanisms, including informal discussion, education, training, and work shifting, were the most usual means of handling a doctor whose performance was poor. Many took a less serious view of deficiencies in performance on manner and attitude and communication, although consultation skills rather than technical skills comprised the greatest number of complaints about doctors. Senior NHS professionals seem reluctant to consider persistently poor consultation skills in the same critical light as they do persistently poor technical practice. These attitudes may need to change with the implementation of clinical governance and updated guidance from the GMC on what constitutes good medical practice.


L-glutamine stimulates intestinal cell proliferation and activates mitogen-activated protein kinases.
We studied the mechanisms by which L-glutamine (Gln), a major fuel for enterocytes, signals proliferation in intestinal epithelial cell lines. Gln was additive to epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) in stimulating DNA synthesis, as assessed by [3H]thymidine incorporation. Extracellular signal-regulated kinases (ERKs) p42mapk and p44mapk and Jun nuclear kinases (JNKs) phosphorylate and activate nuclear transcription factors. Proteins of the c-Jun, ATF-2, and c-Fos families aggregate to form DNA-binding homodimers or heterodimers called activating protein 1 (AP-1). In vitro assays and functional assays of phosphorylation demonstrated that Gln activates both ERKs and JNKs, resulting in a fourfold increase in AP-1-dependent gene transcription. Gln was required for EGF signaling through ERKs. Maximal stimulation of proliferation required approximately 2.5 mM Gln. c-Jun mRNA levels responded to Gln in "Gln-starved" porcine IPEC-J2 cells and in rat IEC-6 cells. Although Gln metabolism is required for the proliferative response, several Gln by-products did not stimulate [3H]thymidine incorporation, with the exception of arginine. Gln may be a unique nutrient for enterocytes, capable of dual signaling and augmenting the effects of growth factors that govern cellular proliferation and repair.


Maya blue: a clay-organic pigment?
Maya Blue, a pigment used by the Mayas in Yucatan, is remarkably stable: the color is not destroyed by hot concentrated mineral acids or by heating to about 250 degrees C. The principal constituent is the colorless mineral attapulgite. It is proposed that the pigment is an adsorption complex of attapulgite and natural indigo; a synthetic equivalent may be prepared from attapulgite and either indoxylester or indigo, or by applying the vat-dyeing technique, with reduced indigo.The low dye content of the pigment (less than 0.5 percent) indicates that the dye is absorbed only on the external surfaces of the attapulgite particles and not throughout the channels in their structures. The complex as such is not stable to acids, but the stability displayed by Maya Blue is achieved simply by heating the complex to from 75 degrees to 150 degrees C for several days. An analogous stable pigment can be prepared from sepiolite and indigo. No stable pigments could be prepared from clays with platelike structures or from zeolites.


Tumour shapes and fully automated range compensation for heavy charged particle radiotherapy.
The idea of a computer-controlled range-compensating system for heavy charged particle radiotherapy, the multibar compensator, is proposed. By stacking multiple energy-absorbing layers along the beam, each of which has structure and behaviour similar to those of a multileaf collimator, variable range compensation will be achieved. The analysis of the conventional range compensators actually used for treatment concluded that the proposed system would not seriously degrade the treatment quality for the most cases, except for tumours in the head and neck region where 1 mm precision may be required. The system will even be able to coexist with the conventional range compensators to provide either method depending on clinical situations.


CourtTime: Generating Actionable Insights into Tennis Matches Using Visual Analytics.
Tennis players and coaches of all proficiency levels seek to understand and improve their play. Summary statistics alone are inadequate to provide the insights players need to improve their games. Spatio-temporal data capturing player and ball movements is likely to provide the actionable insights needed to identify player strengths, weaknesses, and strategies. To fully utilize this spatio-temporal data, we need to integrate it with domain-relevant context meta-data. In this paper, we propose CourtTime, a novel approach to perform data-driven visual analysis of individual tennis matches. Our visual approach introduces a novel visual metaphor, namely 1-D Space-Time Charts that enable the analysis of single points at a glance based on small multiples. We also employ user-driven sorting and clustering techniques and a layout technique that aligns the last few shots in a point to facilitate shot pattern discovery. We discuss the usefulness of CourtTime via an extensive case study and report on feedback from an amateur tennis player and three tennis coaches.


Effects of a triage process conversion on the triage of high-risk presentations.
The objective was to determine effects of a modification in triage process on triage acuity distribution in general and among patients with conditions requiring time-sensitive therapy. The authors retrospectively reviewed triage acuity distributions before and after modification of their triage process that entailed conversion from the Canadian Triage and Acuity Scale (CTAS) to the Emergency Severity Index (ESI). The authors calculated the ratio of the odds of being triaged to a nonemergent level (3, 4, or 5) under ESI to the odds of being triaged as nonemergent under CTAS. The authors calculated sensitivity and specificity of triage to an emergent acuity level (1 or 2) for identifying patients with common presentations who required time-sensitive care. There were shifts from higher to lower acuity levels for all subsets, with odds ratios ranging from 2.80 (95% confidence interval [CI] = 2.75 to 2.86) for all patients to 21.39 (95% CI = 14.66 to 31.21) for patients over 55 years of age with a chief complaint of chest pain. The sensitivity of triage for identifying abdominal pain patients requiring admission to an intensive care unit (ICU) or operating room (OR) or emergency department (ED) death was 80.7% (95% CI = 73.2 to 86.5) before versus 50.8% (95% CI = 43.5 to 58.1) following the transition to ESI. Specificity under CTAS, 55.2% (95% CI = 54.0 to 56.4), was significantly lower than under ESI, 83.6% (95% CI = 82.7 to 84.4). The authors found similar effects for patients presenting with chest pain. Monitoring for changes in the sensitivity of the triage process for detecting patients with potentially time-sensitive conditions should be considered when modifying triage processes. Further work should be done to determine if the decreased sensitivity seen in this study occurs in other institutions converting to ESI, and potential causative factors should be explored.


Age-Related Changes in the Anatomy of Language Regions in Autism Spectrum Disorder.
Impairments in language and communication are core features of autism spectrum disorder (ASD). The anatomy of critical language areas has been studied in ASD with inconsistent findings. We used MRI to measure gray matter volume and asymmetry of Heschl's gyrus, planum temporale, pars triangularis, and pars opercularis in 40 children and adolescents with ASD and 40 typically developing individuals, each divided into younger (7-11 years) and older (12-19 years) cohorts. The older group had larger left planum temporale volume and stronger leftward asymmetry than the younger group, regardless of diagnosis. The pars triangularis and opercularis together were larger in ASD than controls. Correlations between frontal language areas with language and symptom severity scores were significant in younger ASD children. Results suggest similar developmental changes in planum temporale anatomy in both groups, but group differences in pars triangularis and opercularis that may be related to language abilities and autism symptom severity.


The ubiquitin-related protein RUB1 and auxin response in Arabidopsis.
The AXR1 (auxin-resistant) protein, which has features of the ubiquitin-activating enzyme E1, is required for normal response to the plant hormone auxin in Arabidopsis thaliana. ECR1 functions together with AXR1 to activate members of the RUB/NEDD8 family of ubiquitin-related proteins. Extracts from mutant seedlings lacking AXR1 did not promote formation of the RUB-ECR1 thiolester, indicating that AXR1 is the major activity in this tissue. AXR1 was localized primarily to the nucleus of dividing and elongating cells, suggesting that the targets of RUB modification are nuclear. These results indicate that auxin response depends on RUB modification of one or more nuclear proteins.


[Extramedullary anaplastic plasmacytoma].
A case of extramedullary plasmacytoma of the maxillary sinus, locally aggressive, in a 65 years old man is presented. Clinical diagnosis of adenocarcinoma was suspected but the pathological study showed an anaplastic morphology, with little plasmacytic differentiation and lack of stain with cytokeratins and epithelial membrane antigen (EMA), immunohistochemical marker of plasmatic cells, among others. Definitive diagnosis was based on light chain restriction and lack of multiple myeloma.


[Isolation from the environment of strains of microorganisms with glucose oxidase activity].
Strains of microorganisms (13) producing enzyme glucoseoxidase were isolated from various samples of soil. The ability to oxidase glucose in presence of oxygen is most expressed in representatives of genera Aureobasidium, Aspergillus, Penicillium. Media containing the KJ-starch indicator were used at primary step for isolation of microorganisms from the environment. The strain, identified as Aureobasidium pullulans (de Bary) Arnaud, isolated from soil had the greatest glucoseoxidase activity, remained active after lyophilization, grew on the medium, which contained low concentration of glucose and nitrate for candides. Use of its cells as a glucoseoxidase sensor control allowed to detect glucose in the liquids with concentration from 0.027 mM/l.


Paroxysmal nonepileptic events in infancy, childhood, and adolescence.
There are a wide variety of paroxysmal nonepileptic events (PNEEs) in children that can mimic seizures. The type of PNEEs that need to be considered in the differential diagnosis depends on the age of symptom onset and the clinical features. In infants and toddlers, conditions that are relatively common in clinical practice such as apnea, jitteriness, shuddering attacks, and breath-holding spells may not present much of a diagnostic conundrum, whereas unusual conditions such as hyperekplexia may cause concern. Similarly, although most types of migraine are easily distinguished from seizures in school-aged children, certain variants such as the "Alice in Wonderland" syndrome or basilar migraine can create diagnostic confusion. Most types of PNEE are exclusive to childhood; therefore, the pediatrician must be familiar with a variety of physiological processes and pathological entities that can raise concern in parents. The pediatrician is in the unique position of being able to reassure families and/or guide further work-up. Many of the PNEEs in young children require no treatment and resolve spontaneously. It is important to distinguish these episodes from true seizures as to avoid unnecessary testing and pharmacological treatment. This review highlights common PNEEs in children, beginning with the neonatal age group and moving upward to adolescence.


Correlation of Handheld Reflectance Confocal Microscopy With Radial Video Mosaicing for Margin Mapping of Lentigo Maligna and Lentigo Maligna Melanoma.
The management of lentigo maligna (LM) and LM melanoma (LMM) is challenging because of extensive subclinical spread and its occurrence on cosmetically sensitive areas. Reflectance confocal microscopy (RCM) improves diagnostic accuracy for LM and LMM and can be used to delineate their margins. To evaluate whether handheld RCM with radial video mosaicing (HRCM-RV) offers accurate presurgical assessment of LM and LMM margins. This prospective study included consecutive patients with biopsy-proven LM and LMM located on the head and neck area who sought consultation for surgical management from March 1, 2016, through March 31, 2017, at the Dermatology Service of the Memorial Sloan Kettering Cancer Center. Thirty-two patients underwent imaging using HRCM-RV, and 22 patients with 23 LM or LMM lesions underwent staged surgery and contributed to the analysis. Clinical lesion size and area, LM and LMM area based on HRCM-RV findings, surgical defect area estimated by HRCM-RV, and observed surgical defect area. In addition, the margins measured in millimeters estimated for tumor clearance in each quadrant based on HRCM-RV findings were calculated and compared with the surgical margins. Among the 22 patients (12 men and 10 women; mean [SD] age, 69.0 [8.6] years [range, 46-83 years]) with 23 lesions included in the final analysis, the mean (SD) surgical defect area estimated with HRCM-RV was 6.34 (4.02) cm2 and the mean (SD) area of surgical excision with clear margins was 7.74 (5.28) cm2. Overall, controlling for patient age and previous surgery, surgical margins were a mean of 0.76 mm (95% CI, 0.67-0.84 mm; P < .001) larger than the HRCM-RV estimate. Mapping of LM and LMM with HRCM-RV estimated defects that were similar to but slightly smaller than those found in staged excision. Thus, mapping of LM using HRCM-RV can help spare healthy tissue by reducing the number of biopsies needed in clinically uncertain areas and may be used to plan treatment of LM and LMM and counsel patients appropriately.


In vivo and in vitro study of radio-frequency application with a new long linear probe: implication for the maze operation.
The maze operation for atrial fibrillation is effective but highly invasive. We tested, both in vitro and in vivo, a new technique for creating long linear atrial lesions with a custom-made, 25-mm long, stainless-steel, linear probe and a corresponding 500-kHz generator for assistance in the maze operation. In the in vitro study with the isolated canine atria, the power of the delivered radio-frequency energy and the saline irrigating flow rate were changed independently, and the sizes of the lesions were measured. In the in vivo study radio-frequency energy was delivered to 4 portions (ie, the smooth and trabeculated portions of the right and left atria). The sizes of the lesions were measured, and the histologic features of the lesions were examined. Electrical isolation of the right atrial appendage from the remaining right atrium was attempted by using this linear probe. In the in vitro study the size of the lesion became larger as the delivered power was increased, although the lesion was limited when the flow rate was high. In the in vivo study the size of the lesion was equal at the 4 different sites. Histologic examinations demonstrated linear and transmural lesions, and electrophysiologic examinations revealed conduction block between the right atrial appendage and the remaining right atrium. The new original long linear probe was effective for creating transmural linear atrial lesions with the irrigation method, presenting the possibility of an intraoperative technique that mimics the maze procedure.


Discovery of new glomerular disease-relevant genes by translational profiling of podocytes in vivo.
Identifying new biomarkers and therapeutic targets for podocytopathies such as focal segmental glomerulosclerosis (FSGS) requires a detailed analysis of transcriptional changes in podocytes over the course of disease. Here we used translating ribosome affinity purification (TRAP) to isolate and profile podocyte-specific mRNA in two different models of FSGS. We expressed enhanced green fluorescent protein-tagged to ribosomal protein L10a in podocytes under the control of the collagen-1α1 promoter, enabling one-step podocyte-specific mRNA isolation over the course of disease. This TRAP protocol robustly enriched known podocyte-specific mRNAs. We crossed Col1α1-eGFP-L10a mice with the Actn4(-/-) and Actn4(+/K256E) models of FSGS and analyzed podocyte transcriptional profiles at 2, 6, and 44 weeks of age. Two upregulated podocyte genes in murine FSGS (CXCL1 and DMPK) were found to be upregulated at the protein level in biopsies from patients with FSGS, validating this approach. There was no dilution of podocyte-specific transcripts during disease. These are the first podocyte-specific RNA expression data sets during aging and in two models of FSGS. This approach identified new podocyte proteins that are upregulated in FSGS and defines novel biomarkers and therapeutic targets for human glomerular disease.


Rapamycin-induced apoptosis is p53-independent in human prostate carcinoma PC-3 cells.
We have investigated the mechanisms of rapamycin-induced growth inhibition and apoptosis in the PC-3 prostate carcinoma cell line. Rapamycin induced apoptosis as well as the expression of p21(waf1) mRNA and protein, independent of p53. Rapamycin treatment also resulted in: a decrease in cdk2 kinase activity; an increase in hypophosphorylated retinoblastoma protein (pRb); a dephosphorylation of p70 S6 kinase; and, growth-arrest in G(1)-phase of cell cycle. These data suggest that rapamycin-induced growth arrest and apoptosis occur through the p53-independent induction of p21(waf1). Since this induction occurred soon after rapamycin treatment, possibly, the early induction of p21(waf1) and G(1)-arrest are important components of the mechanism by which rapamycin induces apoptosis in PC-3 cells.


Effects of body mass index on maximal work production capacity and aerobic fitness during incremental exercise.
The aim of this study was to investigate the relationship between cardiopulmonary fitness as indicated by maximal work rate (Wmax) production and aerobic capacities (WAT), body mass index (BMI) and heart rate reserve. A total of 60 sedentary subjects (30 males, 30 females, aged 18-25 years) were enrolled in the study. Each subject performed an incremental exercise test (15 W/min) to the limit of tolerance on an electromagnetically-braked cycle ergometer. There was a negative correlation between increased BMI to Wmax capacity per kilogram body weight in male (r=-0.846, P=0.0001) and in female (r=-0.896, P=0.0001) subjects. In addition, W(AT) for each kilogram body weight also negatively correlated with increased BMI in male (r=-0.870, P=0.0001) and in females (r=-0.807, P=0.0001). The heart rate reserve correlated negatively with increasing BMI: r=-0.699, P=0.0001 (males) and r=-0.655, P=0.0001 (females). The results of the present study have suggested that, due to the inverse correlation between BMI, Wmax capacity, aerobic fitness and heart rate reserve, it may be useful to consider BMI in establishing cardiopulmonary fitness in various subjects.


Extracorporeal membrane oxygenation in children with heart disease and genetic syndromes.
Our objective was to evaluate morbidity and mortality associated with extracorporeal membrane oxygenation (ECMO) in children with genetic syndromes and heart disease. We conducted a retrospective review of all children with heart disease and genetic syndromes receiving ECMO during the period January 2000 and March 2012 at Arkansas Children's Hospital, Little Rock. The medical charts were reviewed to obtain the following variables: demographic information, medical and surgical history, laboratory and microbiological, information on organ dysfunction, and outcome characteristics. The outcome variables evaluated in this report included: hospital length of stay (LOS), survival to hospital discharge, and current survival. Outcome data were compared among critically ill children with and without syndromes. During the study period, there were 377 ECMO runs in 336 children with heart disease. Of these, 43 ECMO runs occurred in children with genetic syndromes whereas 334 ECMO runs occurred in children with no genetic abnormality. Children in the group with underlying genetic syndrome were older at the time of ECMO cannulation than the group with no syndrome. During the ECMO run, hospital LOS and mortality were similar in children with and without underlying genetic abnormality. Among genetically abnormal patients, renal insufficiency and need for dialysis were associated with mortality. In this group, 24 patients (56%) were discharged alive. However, only 10 patients are living to date in this cohort. ECMO can be used in children with heart disease and genetic syndromes with good results. The survival rate is high and the complication rate is low.


Despite overall improvement in surgical outcomes since 2000, income-related disparities persist.
Despite improvements in health care, disparities in care still exist and are widening for some health measures. This study examined postsurgical outcomes for patients from low-income areas as compared to outcomes for those from high-income areas in the United States from 2000 to 2009. We found that postsurgical outcomes improved in general, with significant decreases in nine of twelve mortality and patient safety measures and an increase in one measure. Patients from low-income areas had worse surgical outcomes than those from high-income areas for nine of twelve measures in both 2000 and 2009. The disparities in outcomes between low- and high-income groups did not change significantly for nine of the twelve measures. For the three measures that did change significantly, in only two of the cases was the change favorable for patients from low-income areas. These findings have implications for efforts to improve surgical outcomes and health policy and indicate the need for research on the cause of continued disparities in postsurgical outcomes.


Generation of infectious recombinant Adeno-associated virus in Saccharomyces cerevisiae.
The yeast Saccharomyces cerevisiae has been successfully employed to establish model systems for a number of viruses. Such model systems are powerful tools to study the virus biology and in particular for the identification and characterization of host factors playing a role in the viral infection cycle. Adeno-associated viruses (AAV) are heavily studied due to their use as gene delivery vectors. AAV relies on other helper viruses for successful replication and on host factors for several aspects of the viral life cycle. However the role of host and helper viral factors is only partially known. Production of recombinant AAV (rAAV) vectors for gene delivery applications depends on knowledge of AAV biology and the limited understanding of host and helper viral factors may be precluding efficient production, particularly in heterologous systems. Model systems in simpler eukaryotes like the yeast S. cerevisiae would be useful tools to identify and study the role of host factors in AAV biology. Here we show that expression of AAV2 viral proteins VP1, VP2, VP3, AAP, Rep78, Rep52 and an ITR-flanked DNA in yeast leads to capsid formation, DNA replication and encapsidation, resulting in formation of infectious particles. Many of the AAV characteristics observed in yeast resemble those in other systems, making it a suitable model system. Future findings in the yeast system could be translatable to other AAV host systems and aid in more efficient production of rAAV vectors.


A qualitative study of contextual factors' impact on measures to reduce surgery cancellations.
Contextual factors influence quality improvement outcomes. Understanding this influence is important when adapting and implementing interventions and translating improvements into new settings. To date, there is limited knowledge about how contextual factors influence quality improvement processes. In this study, we explore how contextual factors affected measures to reduce surgery cancellations, which are a persistent problem in healthcare. We discuss the usefulness of the theoretical framework provided by the model for understanding success in quality (MUSIQ) for this kind of research. We performed a qualitative case study at Førde Hospital, Norway, where we had previously demonstrated a reduction in surgery cancellations. We interviewed 20 clinicians and performed content analysis to explore how contextual factors affected measures to reduce cancellations of planned surgeries. We identified three common themes concerning how contextual factors influenced the change process: 1) identifying a need to change, 2) facilitating system-wide improvement, and 3) leader involvement and support. Input from patients helped identify a need to change and contributed to the consensus that change was necessary. Reducing cancellations required improving the clinical system. This improvement process was based on a strategy that emphasized the involvement of frontline clinicians in detecting and improving system problems. Clinicians shared information about their work by participating in improvement teams to develop a more complete understanding of the clinical system and its interdependencies. This new understanding allowed clinicians to detect system problems and design adequate interventions. Middle managers' participation in the improvement teams and in regular work processes was important for successfully implementing and adapting interventions. Contextual factors interacted with one another and with the interventions to facilitate changes in the clinical system, reducing surgery cancellations. The MUSIQ framework is useful for exploring how contextual factors influence the improvement process and how they influence one another. Discussing data in relation to a theoretical framework can promote greater uniformity in reporting findings, facilitating knowledge-building across studies.


Long term results of cardiac valve replacement in patients aged 75 years and older.
From June 1978 to December 1989, 158 patients over 75 years of age (mean: 78 years; range 75 to 86 years) underwent 164 valve replacements: 134 in the aortic, 18 in the mitral and 6 in double mitral and aortic positions. One hundred and seven of these valves (66%) were bioprostheses, 93 aortic and 14 mitral and 57 valves (34%) were mechanical prostheses; 47 aortic and 10 mitral. Hospital mortality (less than or equal to 30 days) was 7% (11 patients, all in NYHA class III or IV) but was higher in patients who had undergone associated procedures (9.8%; 6/61 patients) or in patients who had mitral valve replacements (11%) and in double valve replacement (16.6%). Because of a minimal delay of one year, long term follow-up information (100%) was only obtained from the first 110 patients discharged from hospital. Late mortality has been 13.6% and actuarial survival at 11 years was 71.5% +/- 5. Therefore, despite a hospital mortality of more than twice that of patients operated upon under 75 years of age (3.3%), an actuarial survival at 11 years, similar to that of patients under 75 years (77 +/- 5%) and the functional improvement obtained (95% of survivors are NYHA class I or II) certainly justify surgery in these patients. Because of the incidence of anticoagulant related hemorrhages in these patients (1.7% patient year) and since, structural deterioration of the bioprostheses was non existent in this series, a bioprosthesis appears to be the best valvular substitute in patients over 75 years of age.


Corneal epithelial opacity in dysfunctional tear syndrome.
To compare the appearance of the superficial corneal epithelium in patients with dysfunctional tear syndrome (DTS) and that of an asymptomatic control group using laser scanning confocal microscopy and to determine the correlations between confocal microscopic findings and clinical severity parameters. Prospective case-control study. Thirty-one patients with newly diagnosed DTS and 21 asymptomatic control subjects were evaluated for this study. Subjects with DTS were classified into 4 levels of clinical severity (DTS 1 through 4) based on the Delphi dry eye panel report criteria. The Heidelberg Retina Tomograph 2 Rostock Cornea Module (Heidelberg Engineering GmbH, Heidelberg, Germany) laser scanning confocal microscope was used to image the superficial corneal epithelium. Areas of single or multiple opaque superficial epithelial cells were measured as a percentage of the 400 x 400-microm(2) field area in 4 randomly selected confocal images from each eye. Spearman correlations between the confocal findings and severity of symptoms, visual acuity, and ocular surface signs were calculated. The mean area of opaque superficial corneal epithelial cells was significantly greater in DTS patients than in normal subjects (P < .0001). Significant differences were observed between the DTS severity groups and the control group (P < .001), except for the DTS 1 group. The area of opaque cells significantly increased with level of clinical severity. The confocal findings showed significant correlation with clinical severity parameters, including blurred vision symptoms (r = 0.86; P = .0001), best-corrected visual acuity (Spearman r = 0.4; P = .03), conjunctival lissamine green staining scores (Spearman r = 0.4; P = .026), corneal fluorescein staining scores (Spearman r = 0.5; P = .002), and videokeratoscopic surface regularity index (Spearman r = 0.5; P = .02). Morphologic changes in the superficial corneal epithelium of DTS patients detected by laser scanning confocal microscopy correlates with blurred vision symptoms and objective severity parameters. Objective confocal image analysis of the superficial corneal epithelium may prove useful for classifying DTS severity and for monitoring the efficacy of therapies.


Effects of the Low-Level Laser Therapy (LLLT) in the process of healing diabetic foot ulcers.
To evaluate the effects of the low-level laser therapy applying Laser on the tissue repair in ulcer carriers due to diabetes. Sixteen type II diabetic patients, ulcer carriers in the lower limbs, participated in the research from which eight were in the control group and eight were submitted to the low-level laser therapy with a pulsed wave form, visible ray, wave length of 632.8 nm, 30 mW peak power, (Laser - HTM). The application time was of 80 (4J/cm2) seconds. The application was punctual without contact (approximately 1mm of distance), the pen being held in a perpendicular position related to the wound, in equidistant points. There were 12 appointments, of which three were done weekly in alternated days. Photograph records and an application of the brief inventory of pain were done before and after 30 days of follow-up. There was a significant decrease in the size of the wound when compared to the control group (p<0.05). The pain was also reported as having an intense improvement in the treated group. The low-level laser treatment seems to be an efficient method, viable, painless and of low costs concerning the tissue repair ulcers in a diabetic foot.


Career planning courses increase career readiness of graduate and postdoctoral trainees.
Background: Given national calls for intentional career development during graduate and post-graduate scientific training, this study assessed career readiness development within the context of academic career courses. The current study evaluated the effects of academic career courses offered at two institutions that were specifically designed to increase career awareness, interest, and career-related confidence among doctoral students and postdoctoral fellows. Methods: Participants enrolled in a career course at trainees' respective academic institutions and responded to pre- and post-course surveys (n=32, n=148). The paper offers a thematic analysis of each of the two courses using an individualized learning plan career development framework and describes the results of their respective pretest-posttest evaluations which indicated increases in career readiness. Results: Though the format and content provided in each course varied, participation was associated with increases in career readiness. Participants reported increased career-awareness including a greater familiarity with different types of careers overall. Furthermore, interest in tenure track faculty careers increased in both samples, which may assuage fears that exposure to diverse career pathways could reduce interest in academic careers. Transferrable skills, including career planning and awareness also significantly increased. Course participants reported an increase in the number and type of mentors they interacted with beyond their principal faculty mentor (other faculty, professional PhDs, peers, and administrative staff). Conclusions: Findings provide supporting evidence for the benefits of implementing structured career development efforts during PhD training; even with varying content, delivery methods, and instructor type, both academic career courses led to significant gains in career awareness and readiness. Successful development and delivery of academic career courses, with a focus on career planning skills, suggest that institutions can utilize these and are an effective way to prepare PhDs for their transition from training positions into careers.


A Systematic Scoping Review of Media Campaigns to Develop a Typology to Evaluate Their Collective Impact on Promoting Healthy Hydration Behaviors and Reducing Sugary Beverage Health Risks.
Interventions to discourage sugary beverages and encourage water consumption have produced modest and unsustainable behavioral changes to reduce obesity and noncommunicable disease risks. This systematic scoping review examined media campaigns to develop a typology to support healthy hydration nonalcoholic beverage behaviors. Our three-step methodology included the following: (1) review and summarize expert-recommended healthy beverage guidelines; (2) review six English-language electronic databases guided by PRISMA to describe existing campaign types by issue, goal and underlying theory; and (3) develop a media campaign typology to support policies, systems and environments to encourage healthy hydration behaviors. Results showed no international consensus for healthy beverage guidelines, though we describe expert-recommended healthy beverage guidelines for the United States. Of 909 records identified, we included 24 articles describing distinct media campaigns and nine sources that defined models, schemes or taxonomies. The final media campaign typology included: (1) corporate advertising, marketing or entertainment; (2) corporate social responsibility, public relations/cause marketing; (3) social marketing; (4) public information, awareness, education/ health promotion; (5) media advocacy/countermarketing; and (6) political or public policy. This proof-of-concept media campaign typology can be used to evaluate their collective impact and support for a social change movement to reduce sugary beverage health risks and to encourage healthy hydration behaviors.


Short- and long-term survival in treated elderly hypertensive patients with or without diabetes: findings from the Second Australian National Blood Pressure study.
We sought to determine the incidence of newly diagnosed diabetes in treated elderly hypertensive patients and the prognostic impact of diabetes on long-term survival. The Second Australian National Blood Pressure (ANBP2) study randomized 6,083 hypertensive patients aged 65-84 years to angiotensin-converting enzyme inhibitor (ACEI) or thiazide diuretic-based therapy and followed them for a median of 4.1 years. Long-term survival was determined in 5,678 patients over an additional median of 6.9 years after ANBP2 (post-trial). After ANBP2, the cohort was classified into preexisting (7.2%), newly diagnosed (5.6%), and no diabetes (87.2%) groups. A 44% higher incidence of newly diagnosed diabetes was observed in patients randomized to thiazide diuretic compared with ACEI-based treatment. The other predictors of newly diagnosed diabetes were having a higher body mass index, having a higher random blood glucose, and living in a regional location compared to major cities (a geographical classification based on accessibility) at study entry. After completion of ANBP2, compared with those with no diabetes, the preexisting diabetes group experienced higher cardiovascular (hazards ratio (HR) = 1.65; 95% confidence interval (CI) = 1.03-2.65) and all-cause mortality (HR = 1.40; 95% CI = 1.02-1.92) when adjusted for age, sex, and treatment. A similar pattern was observed after including the post-trial period for cardiovascular (HR = 1.52; 95% CI = 1.20-1.93) and all-cause mortality (HR = 1.50; 95% CI = 1.29-1.73). However, when the newly diagnosed group was compared with the no diabetes group, no significant difference was observed in cardiovascular (HR = 0.33; 95% CI = 0.11-1.05) or all-cause mortality (HR = 0.76; 95% CI = 0.47-1.23) either during the ANBP2 trial or including post-trial follow-up (cardiovascular: HR = 0.82; 95% CI = 0.58-1.17; all-cause mortality: HR = 1.04; 95% CI = 0.85-1.27). Long-term presence of diabetes reduces survival. Compared with thiazide diuretics, ACEI-based antihypertensives may delay the development of diabetes in those at risk and thus potentially improve cardiovascular outcome in the elderly.


[Relation between alcoholism and depression based on a review of empirical studies].
The article surveys empirical studies on the relation between alcohol addiction and depression. For a better understanding and interpretation of the results of these empirical since the end of the 'sixties, the author presents first of all a brief historical abstract of the development of classification of depressive disorders and of the definition of alcoholism. In this article, the author restricts his comments to studies conducted since the end of the 'sixties, as self-rating scales or observers-rating scales or standardised interviews have been employed from that time for characterising the pattern of signs and symptoms and for diagnosis, and now widely used diagnostic schemas also became available (ICD-8, Feighner's criteria, DSM-II). For further clarification studies on genetic studies in the patients' families and on the premorbid personality of alcoholics and depressives are utilised for assessment. The results of these empirical studies are interpreted from the "diagnostic viewpoint" of the 'eighties (i.e. from the viewpoint of ICD-9 and DSM III). Suggestions for further research approach are given. The survey shows that depressive moods appear with greater frequency in patients with alcohol abuse or alcoholism who are under inpatient or outpatient treatment. However, such depressions are usually not very intensive; they will mostly subside towards the end of the treatment course. "Primary depression" and "secondary depression" are seen with an incidence rate far beyond the value expected if two diseases would merely coincide at random, in patient populations whenever alcoholism is involved. On the other hand, no increased prevalence rate for alcoholism was seen in first-degree relations of patients with "major depression" and "Bipolar I disorder", compared with a random sample of a healthy population and first-degree relations of such a random sample. To date we can say that a considerably increased incidence of alcohol abuse, but not of alcohol addiction, is definitely present in clinical populations of patients with bipolar disorders. However, because of the lack of studies which differentiate by means of operationalised criteria between manias and hypomanias and between alcohol addiction and alcohol abuse, it has not been clarified to the present time whether alcohol abuse found in these studies is mainly linked to manic/hypomanic or depressive phases, or whether the alcohol abuse is independent of these phases.(ABSTRACT TRUNCATED AT 400 WORDS)


Early metabolite changes after melatonin treatment in neonatal rats with hypoxic-ischemic brain injury studied by in-vivo1H MR spectroscopy.
Melatonin is a promising neuroprotective agent after perinatal hypoxic-ischemic (HI) brain injury. We used in-vivo 1H magnetic resonance spectroscopy to investigate effects of melatonin treatment on brain metabolism after HI. Postnatal day 7 Sprague-Dawley rats with unilateral HI brain injury were treated with either melatonin 10 mg/kg dissolved in phosphate-buffered saline (PBS) with 5% dimethyl sulfoxide (DMSO) or vehicle (5% DMSO and/or PBS) directly and at 6 hours after HI. 1H MR spectra from the thalamus in the ipsilateral and contralateral hemisphere were acquired 1 day after HI. Our results showed that injured animals had a distinct metabolic profile in the ipsilateral thalamus compared to sham with low concentrations of total creatine, choline, N-acetyl aspartate (NAA), and high concentrations of lipids. A majority of the melatonin-treated animals had a metabolic profile characterized by higher total creatine, choline, NAA and lower lipid levels than other HI animals. When comparing absolute concentrations, melatonin treatment resulted in higher glutamine levels and lower lipid concentrations compared to DMSO treatment as well as higher macromolecule levels compared to PBS treatment day 1 after HI. DMSO treated animals had lower concentrations of glucose, creatine, phosphocholine and macromolecules compared to sham animals. In conclusion, the neuroprotective effects of melatonin were reflected in a more favorable metabolic profile including reduced lipid levels that likely represents reduced cell injury. Neuroprotective effects may also be related to the influence of melatonin on glutamate/glutamine metabolism. The modulatory effects of the solvent DMSO on cerebral energy metabolism might have masked additional beneficial effects of melatonin.


Characterization of staurosporine-sensitive mutants of Saccharomyces cerevisiae: vacuolar functions affect staurosporine sensitivity.
Mutations at several loci affect the sensitivity of the yeast Saccharomyces cerevisiae to staurosporine. We report here the characterization of novel staurosporine- and temperature-sensitive mutants (stt). Cloning and integration mapping showed that the genes STT2/ STT6, STT5, STT7, STT8 and STT9 are allelic to VPS18, ERG10, GPI1, VPS34 and VPS11, respectively. The products of ERG10 and GPI1, respectively, catalyze mevalonate and glycosyl phosphatidylinositol anchor synthesis, while VPS18 and VPS11 genes belong to the class C VPS (Vacuolar Protein Sorting) genes, and the VPS34 gene is classified as a class D VPS. Therefore, staurosporine sensitivity is affected by ergosterol and glycolipid biosynthesis and by vacuolar functions. We found that other vps mutants belonging to classes C and D exhibit staurosporine sensitivity, and that they show calcium sensitivity and fail to grow on glycerol as the sole carbon source; both of the last two characteristics are shared by vacuolar H+-ATPase mutants (vma). As vma mutants were also found to show staurosporine-sensitive growth, staurosporine sensitivity is likely to be affected by acidification of the vacuole. Moreover, wild type yeast cells are more sensitive to staurosporine in alkaline media than in acidic media, suggesting that staurosporine is exported from the cytosol by H+/drug antiporters. Pleiotropic drug resistance (PDR) genes also provide some resistance to staurosporine, because deltapdr5, deltasnq2 and deltayor1 strains are more sensitive to staurosporine than the wild-type strain. This suggests that staurosporine is also exported by the ATP-binding cassette (ABC) transporters on the plasma membrane. vma mutants and vps mutants of classes C and D vps are sensitive to hygromycin B and vanadate, while ABC transporter-depleted mutants do not show such sensitivity, indicating that two systems differ in their ability to protect the cell against different types of drug.


One-step site-specific antibody fragment auto-conjugation using SNAP-tag technology.
Antibody-based diagnostic and therapeutic agents play a substantial role in medicine, especially in cancer management. A variety of chemical, genetic and enzymatic site-specific conjugation methods have been developed for equipping antibodies with effector molecules to generate homogeneous antibody conjugates with tailored properties. However, most of these methods are relatively complicated and expensive and require several reaction steps. Self-labeling proteins such as the SNAP-tag are an innovative solution for addressing these challenges. The SNAP-tag is a modified version of the human DNA repair enzyme alkylguanine-DNA alkyltransferase (AGT), which reacts specifically with O(6)-benzylguanine (BG)-modified molecules via irreversible transfer of an alkyl group to a cysteine residue. It provides a simple, controlled and robust site-specific method for labeling antibodies with different synthetic small effector molecules. Fusing a SNAP-tag to recombinant antibodies allows efficient conjugation of BG-containing substrates by autocatalytic, irreversible transfer of the alkyl group to a cysteine residue in the enzyme's active site under physiological conditions and with a 1:1 stoichiometry. This protocol describes how to generate site-specific SNAP-tag single-chain antibody fragment (scFv) conjugates with different types of BG-modified effector molecules. A specific example is included for the design and production of an scFv-photosensitizer conjugate and its characterization as an immuno-theranostic agent. This protocol includes DNA sequences encoding scFV-SNAP-tag fusion proteins and outlines strategies for expression, purification and testing of the resulting scFv-SNAP-tag-based immuno-conjugates. All experiments can be performed by a graduate-level researcher with basic molecular biology skills within an 8-week time frame.


The use of immunochromatographic rapid test for soft tissue remains identification in order to distinguish between human and non-human origin.
Clear identification of soft tissue remains as being of non-human origin may be visually difficult in some cases e.g. due to decomposition. Thus, an additional examination is required. The use of an immunochromatographic rapid tests (IRT) device can be an easy solution with the additional advantage to be used directly at the site of discovery. The use of these test devices for detecting human blood at crime scenes is a common method. However, the IRT is specific not only for blood but also for differentiation between human and non-human soft tissue remains. In the following this method is discussed and validated by means of two forensic cases and several samples of various animals.


[Demonstration of β-1,2 mannan structures expressed on the cell wall of Candida albicans yeast form but not on the hyphal form by using monoclonal antibodies].
Candida albicans is a polymorphic fungus that may be observed as both commensal and opportunistic pathogen in humans. As one of the major components of Candida cell wall structure, mannan plays an important role in the fungus-host cell interaction and in virulence. The ability to switch from yeast to hypha form of microorganism is crutial in the development of C.albicans infections. Hyphal form has different antigenic properties compared to yeast form and structural changes occur in the yeast cell wall during transition from yeast to hypha form. Although there are several factors associated with this transition process, sufficient information is not available. The aim of this study was to investigate the change of configuration in mannan structure found in C.albicans cell wall by using monoclonal antibodies. C.albicans (NIHA 207) serotype A strains were used as test strains throughout the study, together with Salmonella choleraesuis 211 and Salmonella infantis as controls with similar cell wall structures to that of C.albicans. Cultures were maintained on YPD-agar medium by incubating at 28°C for yeast forms, and on YPD-broth medium in a shaking incubator at 37°C for 3-4 hours for the growth of hyphal forms. Cells were harvested in the exponential phase, and after being washed, the mannan content from C.albicans were extracted from pellet by heating in 20 mM sodium citrate buffer for 90 minutes at 125°C. Hybridoma technique was used for the production of monoclonal antibodies. After immunizing the Balb/C mice with antigen, the splenocytes were harvested and fusion was performed between spleen cells and F0 myeloma cells. The clones grown in HAT medium were screened for the presence of antibody producing hybrid cells by ELISA method. The antibody isotypes were determined by using a commercial kit (Pierce Biotechnology, ABD). The culture supernatants which contained monoclonal antibodies were collected and purified according to the ammonium sulphate method. Sandwich ELISA and immunofluorescence (IF) methods have been used to detect the experimental reactions. In our study, highly specific class IgM murine monoclonal antibodies (mAb-2B7) against C.albicans yeast cell wall were obtained from clone 2B7. These antibodies cross-reacted with S.choleraesuis 211 and S.infantis bacteria sharing similar cell wall structure of C.albicans. The existence of mannan β-1,2 bonds on the surface of C.albicans yeast form was confirmed with a commercial monoclonal antibody (mAb-ACMK-1; Matriks Biotek(®), Turkey) specific for those bonds. Besides, mAb-ACMK-1 interacted with C.albicans yeast form and gave intense fluorescence (high positive reaction) in IF method, but no fluorescence (negative) was detected with hyphal form. This data, obtained for the first time with this study, indicates that the mannan β-1,2 bonds are either found infrequently or none in the fungal hyphal wall. Although both monoclonal antibodies recognize the mannan antigen, mAb-2B7 reacted with S.choleraesuis 211, while mAb-ACMK-1 did not, due to the difference of epitope specificity. In conclusion, monoclonal antibodies may facilitate the characterization of antigenic structures of Candida, which will lead for the identification of new determinants that may increase the sensitivity and specificity of commercial tests used for mannan detection in serum.


Molecular evaluation of acute myeloid leukemias.
Traditionally, acute myeloid leukemia (AML) has been diagnosed and classified based on the morphologic and cytochemical criteria of the French-American-British (FAB) classification system. However, more recent studies have demonstrated that the cytogenetic and molecular genetic abnormalities consistently associated with distinct forms of AML confer the most important prognostic information. Each broad category of de novo AML that arises in infants and children, young adults, and the elderly, or, AML arising secondary to antecedent myelodysplasia (MDS) or prior exposure to chemotherapy, radiotherapy, or environmental agents is characterized by distinct cytogenetic and molecular genetic abnormalities. Over the past 15 years, a number of these recurrent cytogenetic abnormalities have been cloned and characterized, yielding valuable insights into the mechanisms of leukemogenesis and providing powerful molecular tools for precise diagnosis and monitoring of minimal residual disease. As cytogenetic and molecular genetic characterization of AML cells is now considered crucial for both diagnostic and therapeutic decision-making, it is essential to have a working knowledge of the molecular basis of AML. This chapter reviews the molecular genetic features of different forms of AML and the new automated molecular technologies for residual disease assessment; the emerging molecular paradigms in this disease that are being exploited for therapeutic decision-making are presented.


Gene therapy for chronic myelogenous leukemia (CML): a retroviral vector that renders hematopoietic progenitors methotrexate-resistant and CML progenitors functionally normal and nontumorigenic in vivo.
Chronic myelogenous leukemia (CML) is a malignant disease of the human hematopoietic stem cell caused by the BCR/ABL gene rearrangement. The only curative therapy is allogeneic transplantation. Although autologous transplants may prolong survival, most patients relapse because of disease persisting in the host and in the graft. Continued administration of chemotherapy after transplant could reduce the incidence of relapse provided that the autograft can be protected by transfer of a drug-resistance gene. However, CML autografts will almost certainly contain malignant stem cells that will also be rendered drug-resistant. The presence of the BCR/ABL oncoprotein is necessary and sufficient for malignant transformation seen in CML. We thus hypothesized that transfer of a vector that combines a drug-resistance gene with anti-BCR/ABL antisense (AS) sequences may allow for posttransplant chemotherapy to decrease persistent disease while rendering inadvertently transduced CML stem and progenitor cells functionally normal. We constructed a retroviral vector, LasBD, that combines the methotrexate (MTX)-resistant tyrosine-22 dihydrofolate-reductase (tyr22-DHFR) gene and AS sequences directed at the b3a2 BCR/ABL breakpoint. b3a2 BCR/ABL containing 32D and MO7e cells were transduced with LasBD and selected in MTX for 14 days. Expression of the AS sequences reduced BCR/ABL mRNA and p210(BCR/ABL) protein levels by 6- to 10-fold in most cells. This subsequently led to the restoration of normal function of BCR/ABL cDNA+ cells: they grew significantly slower in the presence of interleukin-3 (IL-3); they underwent apoptotic cell death when cultured without IL-3; and they had restored expression and function of adhesion receptors. These effects were specific, because LasBD-containing AS sequences directed at the b3a2 BCR/ABL breakpoint did not affect p190(BCR/ABL)-containing cells. LasBD also rendered 20% to 30% of primary Ph- and Ph+ CD34(+) cells MTX-resistant and decreased BCR/ABL mRNA levels in MTX resistant Ph+ CD34(+) cells by 10-fold. Expression of the MTX-resistant DHFR gene and the AS sequences has been stable for at least 1 year in vitro and for more than 70 days in vivo. Finally, LasBD decreased tumorigenicity of 32DBCR/ABL cells in vivo by 3 to 4 logs. In conclusion, the tyr22-DHFR gene in the LasBD vector can protect normal hematopoietic cells from MTX-mediated toxicity, whereas the AS sequences in LasBD can suppress expression of the BCR/ABL gene and restore normal function of BCR/ABL cDNA-containing cells. The LasBD vector may therefore prove to be an extremely useful adjunct in autologous transplantation for CML.


Heart rate variability improves in 3-5-year-old children following a 6-month physical activity-based intervention: the Active Early Learning (AEL) cluster randomised controlled trial.
Heart rate variability (HRV) measurement provides non-invasive assessment of autonomic stability and cardiometabolic disease risk. Insufficient physical activity in early childhood may contribute to negative cardiometabolic health. The Active Early Learning (AEL) study was a 6-month randomised controlled trial investigating the effects of a physical activity-based program incorporating movement within the daily curriculum of preschool children. The current study assessed the effects of the AEL intervention on HRV as a measure of cardiac vagal control. Children aged between 3-5 years and enrolled in a preschool with an attendance of ≥15 children were eligible. Physical activity was recorded using an Actigraph wGT3x accelerometer worn at the waist of participants over 3 consecutive days. A Polar H10 chest strap measured HRV with the HF-band and RMSSD representing cardiac vagal control. After 6 months of the AEL trial, linear mixed model analyses revealed a significant intervention effect for increased HF (p = 0.044). The control group did not demonstrate changes in cardiac vagal control after the intervention ceased. Independent of age, sex, physical activity and BMI, the AEL study elicited significant improvements in the cardiac vagal control of participants who received the intervention. Findings highlight the importance of investigating HRV for assessing the cardiometabolic health in young children. ANZCTR trial registration number: ACTRN12619000638134. Novelty: The AEL curriculum improved child HRV independent of age, sex, physical activity and BMI. Heart rate and RR intervals did not demonstrate changes for the intervention and control groups. Multivariate programs for developing physical competence, confidence, knowledge and motivation may improve child health.


The Degradome database: mammalian proteases and diseases of proteolysis.
The degradome is defined as the complete set of proteases present in an organism. The recent availability of whole genomic sequences from multiple organisms has led us to predict the contents of the degradomes of several mammalian species. To ensure the fidelity of these predictions, our methods have included manual curation of individual sequences and, when necessary, direct cloning and sequencing experiments. The results of these studies in human, chimpanzee, mouse and rat have been incorporated into the Degradome database, which can be accessed through a web interface at http://degradome.uniovi.es. The annotations about each individual protease can be retrieved by browsing catalytic classes and families or by searching specific terms. This web site also provides detailed information about genetic diseases of proteolysis, a growing field of great importance for multiple users. Finally, the user can find additional information about protease structures, protease inhibitors, ancillary domains of proteases and differences between mammalian degradomes.


Mechanisms of Internalization of Maltose-Modified Poly(propyleneimine) Glycodendrimers into Leukemic Cell Lines.
Poly(propyleneimine) dendrimers of fourth generation partially modified with maltose (open shell structure, PPI-m OS) have been proposed as carriers for nucleotide anticancer drugs. The aim of this work was to provide basic insight into interactions between fluorescently labeled PPI-m dendrimer and two distinct leukemia cell models: CCRF-1301 lymphoid cell line and HL-60 myeloid cell line. We applied qualitative confocal imaging and quantitative flow cytometry, as well as trypan blue quenching and pharmacological inhibition, to investigate the course, kinetics, and molecular mechanisms of internalization of nanoparticles. CCRF-1301 cells take up glycodendrimer macromolecules via a relatively slow, adsorptive endocytosis process, which is cholesterol-dependent, clathrin- and caveolin-independent, and not followed by recycling or exocytosis. Morphological features of this phenomenon point to the involvement of aggregation-induced cell polarity changes (capping). In HL-60 cells, internalization is very fast, independent of binding to the cell surface, and proceeds from the fluid phase via a classical clathrin-dependent mechanism, ending up in an endolysosomal compartment from which it is not further released. This substantial difference in internalization rate and mechanism between two cell types has important repercussions for potential application of this class of glycodendrimers as drug delivery agents.


[Metabolic correction of dyslipidemia in patients with nonalcoholic fatty liver disease as a new therapy policy].
To study the impact of infusion therapy with the metabolic modulator remaxol on lipid metabolic parameters and target organ (liver, kidney) function in metabolic syndrome (MS). The investigation enrolled 90 patients (54 men and 36 women) with primary nonalcoholic steatohepatitis that was associated with insulin-resistance and MS; their age was 21 to 77 years. Every day the study group patients (n = 50) took as a component of combination therapy the metabolic hepatoprotective modulator remaxol intravenously in a dropwise manner in a dose of 400 ml once daily; the comparison group patients (n = 40) received ademetionine 400 mg diluted in 400 ml of isotonic sodium chloride. The duration of infusion therapy was 11 days. Infusion therapy with remaxol caused a pronounced blood lipid composition-regulating effect, by reducing the level of major atherogenic lipids (total cholesterol, triglycerides) and improving liver function and renal nitrogen-excreting and filtration function in patients with Stage IV diabetic nephropathy in the presence of MS. Therapy with the metabolic hepatoprotective modulator remaxol ensures reliable metabolic control and multifactorial correction of risk factors of organ lesions in MS: cardio-, hepato-, and nephroprotection.


Surface waves in two-photon photorefractive media.
We present the evolution equation of surface waves due to the two-photon photorefractive effect. It is shown theoretically that the surface waves can be supported by two-photon photorefractive media. The spatial frequency of photorefractive surface waves can be changed by an applied external electric field, which indicates a method for transforming the surface waves between high-frequency modes and low-frequency modes.


Spontaneous mutation in the COL6A2 gene causing Ullrich congenital muscular dystrophy type 1 in a Chinese child: A case report.
Mutations in the gene encoding type VI collagen cause Bethlem myopathy (MIM 158810) and Ullrich congenital muscular dystrophy (MIM 254090); 2 diseases previously recognized as completely independent, and have been increasingly recognized. However, collagen-related myopathy caused by intron variation in the COL6 gene is rarely reported in China. Ullrich congenital muscular dystrophy is an autosomal recessive disorder that leads to severe muscle weakness with early onset. Thus, children may never walk independently, with proximal joint contractures and significant hyperelastic distal joints, and have early respiratory failure. Therefore, timely diagnosis and treatment are important. We report a spontaneous mutation in the COL6A2 gene causing Ullrich congenital muscular dystrophy type 1 in a pediatric patient. A boy aged 4 years was unable to walk independently, could sit alone for a short time, and his motor development was delayed and had regressed after 1 year of age. He had a high palatal arch and a through palm with localized transverse lines running laterally from the palm. Electromyography showed an impaired neurogenic source, and whole-exon gene sequencing revealed a spontaneous heterozygous mutation in the COL6A2 gene (c.955-2A>G), which was determined to be a pathogenic mutation according to the American Guidelines of the College of Medical Genetics. This child has a delayed motor development, high osprey arch and a through palm with localized transverse lines running laterally from the palm, and regression of motor development after the age of 1 year. Whole exon examination showed spontaneous mutation of the COL6A2 gene; thus, the child was diagnosed with UCMD type 1. At present, there is no special treatment for this disease, and treatment is mainly symptomatic and supportive. The child underwent home massage, rehabilitation training, oral folic acid tablets, vitamins and coenzyme Q10. During the subsequent follow-up period, the patient can now sit alone for a short period of time. We report a case of spontaneous mutation in the COL6A2 gene causing Ullrich congenital muscular dystrophy type 1 in a pediatric patient, expanding the phenotypic spectrum of the disease and enriching the human gene pool.


Systematic review of prognostic factors predicting outcome in non-surgically treated patients with sciatica.
Identification of prognostic factors for surgery in patients with sciatica is important to be able to predict surgery in an early stage. Identification of prognostic factors predicting persistent pain, disability and recovery are important for better understanding of the clinical course, to inform patient and physician and support decision making. Consequently, we aimed to systematically review prognostic factors predicting outcome in non-surgically treated patients with sciatica. A search of Medline, Embase, Web of Science and Cinahl, up to March 2012 was performed for prospective cohort studies on prognostic factors for non-surgically treated sciatica. Two reviewers independently selected studies for inclusion and assessed the risk of bias. Outcomes were pain, disability, recovery and surgery. A best evidence synthesis was carried out in order to assess and summarize the data. The initial search yielded 4392 articles of which 23 articles reporting on 14 original cohorts met the inclusion criteria. High clinical, methodological and statistical heterogeneity among studies was found. Reported evidence regarding prognostic factors predicting the outcome in sciatica is limited. The majority of factors that have been evaluated, e.g., age, body mass index, smoking and sensory disturbance, showed no association with outcome. The only positive association with strong evidence was found for leg pain intensity at baseline as prognostic factor for subsequent surgery.


NFATc1 affects mouse splenic B cell function by controlling the calcineurin--NFAT signaling network.
By studying mice in which the Nfatc1 gene was inactivated in bone marrow, spleen, or germinal center B cells, we show that NFATc1 supports the proliferation and suppresses the activation-induced cell death of splenic B cells upon B cell receptor (BCR) stimulation. BCR triggering leads to expression of NFATc1/αA, a short isoform of NFATc1, in splenic B cells. NFATc1 ablation impaired Ig class switch to IgG3 induced by T cell-independent type II antigens, as well as IgG3(+) plasmablast formation. Mice bearing NFATc1(-/-) B cells harbor twofold more interleukin 10-producing B cells. NFATc1(-/-) B cells suppress the synthesis of interferon-γ by T cells in vitro, and these mice exhibit a mild clinical course of experimental autoimmune encephalomyelitis. In large part, the defective functions of NFATc1(-/-) B cells are caused by decreased BCR-induced Ca(2+) flux and calcineurin (Cn) activation. By affecting CD22, Rcan1, CnA, and NFATc1/αA expression, NFATc1 controls the Ca(2+)-dependent Cn-NFAT signaling network and, thereby, the fate of splenic B cells upon BCR stimulation.


Mechanisms of facilitation of synaptic glutamate release by nicotinic agonists in the nucleus of the solitary tract.
The nucleus of the solitary tract (NTS) is the principal integrating relay in the processing of visceral sensory information. Functional nicotinic acetylcholine receptors (nAChRs) have been found on presynaptic glutamatergic terminals in subsets of caudal NTS neurons. Activation of these receptors has been shown to enhance synaptic release of glutamate and thus may modulate autonomic sensory-motor integration and visceral reflexes. However, the mechanisms of nAChR-mediated facilitation of synaptic glutamate release in the caudal NTS remain elusive. This study uses rat horizontal brainstem slices, patch-clamp electrophysiology, and fluorescent Ca(2+) imaging to test the hypothesis that a direct Ca(2+) entrance into glutamatergic terminals through active presynaptic non-α7- or α7-nAChR-mediated ion channels is sufficient to trigger synaptic glutamate release in subsets of caudal NTS neurons. The results of this study demonstrate that, in the continuous presence of 0.3 μM tetrodotoxin, a selective blocker of voltage-activated Na(+) ion channels, facilitation of synaptic glutamate release by activation of presynaptic nAChRs (detected as an increase in the frequency of miniature excitatory postsynaptic currents) requires external Ca(2+) but does not require activation of presynaptic Ca(2+) stores and presynaptic high- and low-threshold voltage-activated Ca(2+) ion channels. Expanding the knowledge of mechanisms and pharmacology of nAChRs in the caudal NTS should benefit therapeutic approaches aimed at restoring impaired autonomic homeostasis.


[A safety suture for sclerotomy in vitrectomy (author's transl)].
A safety suture with twisted 6-0 silk material for immediate closure of a sclerotomy wound after pars plana vitrectomy is described. The needle is first carried about 5 mm intrasclerally toward the edge of the sclerotomy and, after an oblique pass across the scleral incision, another intrascleral passage of 5 mm follows on the opposite side (Fig. 1). Bimanual stretching of the safety suture (Fig. 2) by the assistant provides a watertight adaptation of the sclerotomy and facilitates the placing of about four 10-0 interrupted nylon sutures without loss of intraocular pressure. After closing the sclerotomy, the safety suture is cut close to the sclera, and the remaining end of the suture is gently pulled out of the sclera.


Performance and microbial ecology of air-cathode microbial fuel cells with layered electrode assemblies.
Microbial fuel cells (MFCs) can be built with layered electrode assemblies, where the anode, proton exchange membrane (PEM), and cathode are pressed into a single unit. We studied the performance and microbial community structure of MFCs with layered assemblies, addressing the effect of materials and oxygen crossover on the community structure. Four MFCs with layered assemblies were constructed using Nafion or Ultrex PEMs and a plain carbon cloth electrode or a cathode with an oxygen-resistant polytetrafluoroethylene diffusion layer. The MFC with Nafion PEM and cathode diffusion layer achieved the highest power density, 381 mW/m(2) (20 W/m(3)). The rates of oxygen diffusion from cathode to anode were three times higher in the MFCs with plain cathodes compared to those with diffusion-layer cathodes. Microsensor studies revealed little accumulation of oxygen within the anode cloth. However, the abundance of bacteria known to use oxygen as an electron acceptor, but not known to have exoelectrogenic activity, was greater in MFCs with plain cathodes. The MFCs with diffusion-layer cathodes had high abundance of exoelectrogenic bacteria within the genus Geobacter. This work suggests that cathode materials can significantly influence oxygen crossover and the relative abundance of exoelectrogenic bacteria on the anode, while PEM materials have little influence on anode community structure. Our results show that oxygen crossover can significantly decrease the performance of air-cathode MFCs with layered assemblies, and therefore limiting crossover may be of particular importance for these types of MFCs.


Mitochondrial myopathy of childhood associated with mitochondrial DNA depletion and a homozygous mutation (T77M) in the TK2 gene.
The mitochondrial DNA depletion syndrome is an autosomal recessive disorder of infancy or childhood characterized by decreased mitochondrial DNA copy number in affected tissues. Mutations in 2 genes involved in deoxyribonucleotide metabolism, the deoxyguanosine kinase gene (DGK) and the thymidine kinase 2 gene (TK2), have been related to this syndrome. To describe 3 siblings with the myopathic form of mitochondrial DNA depletion syndrome and a homozygous mutation in the TK2 gene. These children developed normally until 12 to 16 months of age, when they started showing difficulty walking, which rapidly progressed to severe limb weakness. They died of respiratory failure between the ages of 23 and 40 months. Histochemical and biochemical studies of respiratory chain complexes were performed in muscle biopsy specimens. The whole coding region of the TK2 gene was sequenced. Muscle biopsy showed ragged-red cytochrome-c oxidase-negative fibers. All affected siblings had markedly decreased activities of respiratory chain complexes. Southern blot analysis showed severe reduction of the mitochondrial DNA-nuclear DNA ratio in muscle biopsy specimens from all patients, indicating 80% to 90% mitochondrial DNA depletion. Sequencing of the TK2 gene showed a homozygous C-->T transition at nucleotide 228 in exon 5, which changes a threonine to a methionine at position 77 (T77M). These results document the importance of screening the TK2 gene in patients with myopathic mitochondrial DNA depletion syndrome and confirm that exon 5 is a "hot spot" for TK2 mutations.


Microcalorimetric study of adsorption and disassembling of virus-like particles on anion exchange chromatography media.
Chromatographic purification of virus-like particles (VLPs) is important to the development of modern vaccines. However, disassembly of the VLPs on the solid-liquid interface during chromatography process could be a serious problem. In this study, isothermal titration calorimetric (ITC) measurements, together with chromatography experiments, were performed on the adsorption and disassembling of multi-subunits hepatitis B virus surface antigen virus-like particles (HB-VLPs). Two gigaporous ion-exchange chromatography (IEC) media, DEAE-AP-280 nm and DEAE-POROS, were used. The application of gigaporous media with high ligand density led to significantly increased irreversible disassembling of HB-VLPs and consequently low antigen activity recovery during IEC process. To elucidate the thermodynamic mechanism of the effect of ligand density on the adsorption and conformational change of VLPs, a thermodynamic model was proposed. With this model, one can obtain the intrinsic molar enthalpy changes related to the binding of VLPs and the accompanying conformational change on the liquid-solid interface during its adsorption. This model assumes that, when intact HB-VLPs interact with the IEC media, the total adsorbed proteins contain two states, the intact formation and the disassembled formation; accordingly, the apparent adsorption enthalpy, ΔappH, which can be directly measured from ITC experiments, presents the sum of three terms: (1) the intrinsic molar enthalpy change associated to the binding of intact HB-VLPs (ΔbindHintact), (2) the intrinsic molar enthalpy change associated to the binding of HB-VLPs disassembled formation (ΔbindHdis), and (3) the enthalpy change accompanying the disassembling of HB-VLPs (ΔconfHdis). The intrinsic binding of intact HB-VLPs and the disassembled HB-VLPs to both kinds of gigaporous media (each of which has three different ligand densities), were all observed to be entropically driven as indicated by positive values of ΔbindHintact and ΔbindHdis; while the nagative ΔconfHdis values suggested a spontenous enthalpy-driven process for the forming of HB-VLPs disassembled formation at all conditions studied. As ligand density increases, ΔconfHdis became more negative, which was in agreement with the findings from chromatography experiments, that higher ligand density leads to more serious disassembling of HB-VLPs. Results from thermodynamic studies provided us insight understanding on the mechanism of adsorption and conformational change of VLPs, as well as the effect of ligand densities on the structural stability of VLPs during IEC process.


A new phylum of Archaea represented by a nanosized hyperthermophilic symbiont.
According to small subunit ribosomal RNA (ss rRNA) sequence comparisons all known Archaea belong to the phyla Crenarchaeota, Euryarchaeota, and--indicated only by environmental DNA sequences--to the 'Korarchaeota'. Here we report the cultivation of a new nanosized hyperthermophilic archaeon from a submarine hot vent. This archaeon cannot be attached to one of these groups and therefore must represent an unknown phylum which we name 'Nanoarchaeota' and species, which we name 'Nanoarchaeum equitans'. Cells of 'N. equitans' are spherical, and only about 400 nm in diameter. They grow attached to the surface of a specific archaeal host, a new member of the genus Ignicoccus. The distribution of the 'Nanoarchaeota' is so far unknown. Owing to their unusual ss rRNA sequence, members remained undetectable by commonly used ecological studies based on the polymerase chain reaction. 'N. equitans' harbours the smallest archaeal genome; it is only 0.5 megabases in size. This organism will provide insight into the evolution of thermophily, of tiny genomes and of interspecies communication.


Applying the capability, opportunity, motivation, and behavior model to identify opportunities to increase pharmacist comfort dispensing naloxone in Texas: A structural equation modeling approach.
The prevalence of opioid use and misuse in the United States contributed to 48,000 opioid related deaths in 2018. Naloxone, a potent opioid reversal agent, can be dispensed by pharmacists without a prescription, however few do so. Previous studies on naloxone dispensing have contributed to our understanding of the determinants of naloxone in community pharmacy, however, none have focused on comprehensive behavioral change. This study utilized the Capability, Opportunity, Motivation, and Behavior (COM-B) model, a behavioral change and intervention design framework, to examine community pharmacists' comfort dispensing naloxone. A 48-item questionnaire grounded in the COM-B and theoretical domains framework was developed and mailed to 1,000 community pharmacists in Texas, USA using a modified Dillman cross-sectional survey design. Confirmatory factor analysis was used to refine and establish dimensionality of the hypothesized scales and structural equation modeling was used to estimate the fit of the COM-B in explaining pharmacists' comfort dispensing naloxone. The usable response rate was 19.4%. Of surveyed pharmacists, 29.7% had ever had a patient request naloxone and 35.1% had dispensed naloxone without a prescription. Capability and opportunity explained 60% of the variance in motivation. Opportunity and motivation were the most salient predictors of comfort dispensing naloxone. Together, capability, opportunity, and motivation explained 78.1% of variance in pharmacists' comfort dispensing naloxone, indicating that the COM-B model is useful in this setting. Despite previous findings, policy interventions to increase naloxone dispensing should go beyond providing additional education to the pharmacy workforce. Rather, these results suggest that a complex intervention designed with pharmacist input that enables them to act autonomously and evaluate whether patients need naloxone may increase their comfort dispensing. Without collaboration from pharmacy and managed care corporations, dissemination efforts will continue to be limited.


The influence of relationships on the meaning making process: patients' perspectives.
The diagnosis of a chronic or life limiting illness followed by treatment often requires an adjustment to life goals and expectations. With added existential concerns, patients' struggle to redefine life meaning while also finding ways to alleviate any distress that may occur. Central to the work of many scholars, meaning making is thought to be a vital component of negotiating traumatic life events while also essential to the positive adjustment in chronic illness and healing. Information gained from science about meaning making is an important link to the medical community as it provides physicians with insight to increase patient centered care. The purpose of this qualitative study was to expand our understanding of meaning making for an individual diagnosed with a chronic or life limiting illness. Also, to explore the connection, if any, to how meaning making may lead to an outcome of psychosocial spiritual healing or exacerbate distress. The goal of this secondary data analysis was to examine the influences of meaning making to determine its impact on a patient's sense of healing. This study utilized data collected during in-person interviews using a convenience sample of 30 palliative care patients. The original study was conducted at three different locations: the National Institutes of Health Clinical Center (NIH), a large research institution in Bethesda, Maryland; Johns Hopkins Suburban Hospital, a community hospital in Bethesda, Maryland; and Mobile Medical Care (Mobile Med), a community clinic located in Rockville, Maryland. A total of 56 potential participants were approached based on convenience sampling with 30 participants enrolled (54%). The overall theme that emerged indicated a strong emphasis on meaning making through relationships, specifically an increase of meaning in family relationships, the connection to friends, and a change in compassion towards others. Further investigation is needed to explore relationships as a variable in finding meaning during life limiting illness among patients, loved ones and their physicians. It is clear that developing meaning is a central mechanism to the construct of healing.


Robust Unsupervised Arousal Rating: A Rule-Based Framework with Knowledge-Inspired Vocal Features.
Studies in classifying affect from vocal cues have produced exceptional within-corpus results, especially for arousal (activation or stress); yet cross-corpora affect recognition has only recently garnered attention. An essential requirement of many behavioral studies is affect scoring that generalizes across different social contexts and data conditions. We present a robust, unsupervised (rule-based) method for providing a scale-continuous, bounded arousal rating operating on the vocal signal. The method incorporates just three knowledge-inspired features chosen based on empirical and theoretical evidence. It constructs a speaker's baseline model for each feature separately, and then computes single-feature arousal scores. Lastly, it advantageously fuses the single-feature arousal scores into a final rating without knowledge of the true affect. The baseline data is preferably labeled as neutral, but some initial evidence is provided to suggest that no labeled data is required in certain cases. The proposed method is compared to a state-of-the-art supervised technique which employs a high-dimensional feature set. The proposed framework achieves highly-competitive performance with additional benefits. The measure is interpretable, scale-continuous as opposed to discrete, and can operate without any affective labeling. An accompanying Matlab tool is made available with the paper.


Polypharmacy, potentially inappropriate medications and associated factors among older adults with hypertension in primary care.
to identify the prevalence and associations of polypharmacy and potentially inappropriate medication use among older adults with hypertension treated in primary care. a cross-sectional study carried out with older adults with hypertension treated at a Family Health Strategy unit. Data collection included analysis of medical records, interviews and multidimensional assessment of older adults. Socio-demographic information and clinical variables were collected. Statistical analysis was performed by multiple logistic regression. polypharmacy prevalence was 38.09%, and potentially inappropriate medication (PIM), 28.57%. There was a significant association between polypharmacy and PIM use, altered sleep and ethnicity. PIM use was associated with polypharmacy, worse family functioning, and absence of a caregiver. Cognitive decline reduces the prevalence of these medications. polypharmacy and PIM use among older adults with hypertension represent a problem in this population, especially among the most vulnerable.


Loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype in non-small cell lung cancer.
The development of metastases is the main reason for cancer-related death in non-small cell lung cancer (NSCLC). The initiation of metastasis involves an increase in cell motility mediated by the loss of cell-cell adhesion caused by E-cadherin repression, in a process commonly known as epithelial-to-mesenchymal transition. A role for microRNA-200 family members in regulating epithelial-to-mesenchymal transition has recently been indicated but data about their expression in lung tumors is still unavailable. The present study investigated the expression of miR-200c in a panel of NSCLC cell lines (n = 9), and a strong inverse correlation with invasion was detected. Reintroduction of miR-200c into highly invasive/aggressive NSCLC cells induced a loss of the mesenchymal phenotype by restoring E-cadherin and reducing N-cadherin expression, and inhibited in vitro cell invasion as well as in vivo metastasis formation. Moreover, miR-200c overexpression restored the sensitivity of NCI-H1299 cells to cisplatin and cetuximab. Hypermethylation of the promoter region was found to be responsible for the loss of miR-200c in invasive cells, as evaluated by 5-aza-2'-deoxycytidine treatment, methylation-specific PCR, and bisulfite sequencing. In primary tumor specimens obtained from 69 patients with consecutively resected NSCLC, lower miR-200c expression levels were found to be associated with a poor grade of differentiation (P = 0.04), a higher propensity to lymph node metastases (P < 0.01), and with a lower E-cadherin expression (P = 0.01). These data indicate that the loss of miR-200c expression induces an aggressive, invasive, and chemoresistant phenotype, and that assessment of its expression could contribute to a better clinicopathologic definition of patients with NSCLC.


[Ciliated hepatic foregut cysts: a case report].
The ciliated hepatic foregut cysts (CHFC) are uncommon benign lesions with columnar ciliated epithelium covering a connective lapse tissue. They are solitary uniloculate cysts localized in the left lobe of the liver. The diagnosis is made occasionally during autopsy or imaging studies for not related symptoms. The Authors report a case of CHFC with a review of the literature that allowed them to find only 60 cases.


[The use of the basic drug chart at the first level of care].
This study presents the analysis of the prescriptions given 2,782 clinical encounters. These clinical encounters were directly observed and recorded by trained observers in 164 health centers of the Federal District and nine states of the Mexican Republic. It was found that 70.9 per cent of the patients received a drug prescription. Sixty per cent of the compounds prescribed did not belong to the basic list of drugs. An strong influence of advertising by medical agents was detected in the use of some poly-drugs. Some specific needs for training and continued education of the physicians in the first level of care.


Serum Cytokine Profiles in Infants with Atopic Dermatitis.
Atopic dermatitis (AD) in infancy is believed to have distinct features as compared to AD in other age groups, and little is known about cytokine production in infants with AD. We aimed to measure the serum cytokine levels of infants with atopic dermatitis and evaluate the association of new anti-inflammatory cytokines with the disease. Eighty-one infant patients with AD and 52 healthy controls were involved in this study. The serum levels of major pro- and anti-inflammatory cytokines of the T-helper (Th) subtypes, as well as more recently defined interleukins (IL-27, IL-35, and IL-37), were measured using the ELISA method. The serum levels of IL-35, IL-5, and interferon (IFN)-γ were found to be significantly higher, while the levels of transforming growth factor (TGF)-β1 and IL-13 were found to be significantly lower in patients with AD as compared to controls. There was no statistically significant correlation between serum cytokine levels and objective SCORAD index or total immunoglobulin (Ig) E levels. We did not observe prominent serum Th2 polarization in atopic infants. The immunopathogenesis of atopy onset at an early age may be more complicated than that at older ages.


The physical and mental health effects of housing homeless people: A systematic review.
Housing is a significant determinant of health and is widely accepted as a key solution to address some of the health disparities that exist among the homeless. It is estimated that 150 million people worldwide are homeless, and approximately 1.8 billion lack adequate housing. However, understanding of how housing has a positive impact on the health of the homeless remains unclear and underdeveloped. This systematic review investigates intervention studies that report on the physical and mental health effects of housing homeless persons. A search of PubMed, PsycINFO, EBSCOHost-Academic Search Complete and the Cochrane Library was conducted for peer-reviewed articles published in English from 1999 to 2020 that had a combination of at least one housing intervention and health outcome, with a homeless sample. Three previous reviews and 24 studies were included for analysis. Most of the studies (n = 20) encompassed permanent supportive housing interventions that emphasised placing homeless people with mental illness directly into affordable housing with access to support services. The primary health outcomes reported were general physical and mental health, well-being, and quality of life. Despite inconsistent findings and significant issues identified in the reviewed literature, housing (in the short term) improves some aspects of health in homeless populations with human immunodeficiency virus, anxiety and depression.


Texture classification using spectral histograms.
Based on a local spatial/frequency representation,we employ a spectral histogram as a feature statistic for texture classification. The spectral histogram consists of marginal distributions of responses of a bank of filters and encodes implicitly the local structure of images through the filtering stage and the global appearance through the histogram stage. The distance between two spectral histograms is measured using chi(2)-statistic. The spectral histogram with the associated distance measure exhibits several properties that are necessary for texture classification. A filter selection algorithm is proposed to maximize classification performance of a given dataset. Our classification experiments using natural texture images reveal that the spectral histogram representation provides a robust feature statistic for textures and generalizes well. Comparisons show that our method produces a marked improvement in classification performance. Finally we point out the relationships between existing texture features and the spectral histogram, suggesting that the latter may provide a unified texture feature.


An oxidized extracellular oxidation-reduction state increases Nox1 expression and proliferation in vascular smooth muscle cells via epidermal growth factor receptor activation.
To examine the effect of an oxidized extracellular oxidation-reduction (redox) state (E(h)) on the expression of NADPH oxidases in vascular cells. The generation of reactive oxygen species by NADPH oxidase (Nox)-based NADPH oxidases activates redox-dependent signaling pathways and contributes to the development of "oxidative stress" in vascular disease. An oxidized plasma redox state is associated with cardiovascular disease in humans; however, the cellular mechanisms by which the extracellular redox state may cause disease are not known. Aortic segments and cultured aortic smooth muscle cells were exposed to E(h) between -150 mV (reduced) and 0 mV (oxidized) by altering the concentration of cysteine and its disulfide, cystine, the predominant redox couple in plasma. A more oxidized E(h) increased the expression of Nox1 and resulted in Nox1-dependent proliferation of smooth muscle cells. Oxidized E(h) rapidly induced epidermal growth factor receptor phosphorylation via shedding of epidermal growth factor-like ligands from the plasma membrane and caused extracellular signal-regulated kinase 1/2-dependent phosphorylation of the transcription factors activating transcription factor-1 and cAMP-response element-binding protein. Inhibition of epidermal growth factor receptor or extracellular signal-regulated kinase 1/2 activation, or addition of small interference RNA to activating transcription factor-1, prevented the increase in Nox1 expression. Our results identify a novel mechanism by which extracellular oxidative stress increases expression and activity of Nox1 NADPH oxidase and contributes to vascular disease.


Incidence and Case Fatality at the County Level as Contributors to Geographic Disparities in Stroke Mortality.
Is the high stroke mortality in the Southeastern parts of the United States driven by differences in stroke incidence or case-fatality? This question remains unanswered. Differences in incidence would underscore the need for stroke prevention, while differences in case fatality would call for improved stroke care. Quartiles of US counties were defined by stroke mortality, and this gradient was related with stroke incidence and stroke case fatality in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, where 1,317 incident stroke events (of which 242 were fatal) occurred among 29,650 participants. There was a significant (p = 0.0025) gradient of fatal stroke events in REGARDS (quartile 4 vs. quartile 1 (Q4/Q1) hazard ratio 1.95, 95% CI 1.35-2.81), demonstrating the consistency of REGARDS with national mortality data. The gradient for incident stroke (fatal + nonfatal) was also significant (p = 0.0023; Q4/Q1 hazard ratio 1.29, 95% CI 1.10-1.52). The gradient for stroke case-fatality was marginally significant (p = 0.058), though the OR for Q4/Q1 (1.71, 95% CI 1.13-2.25) was large. Both stroke incidence and case-fatality in REGARDS appear to be contributing, underscoring the need for strengthening both stroke prevention and acute stroke care in order to reduce the disparity.


Markers of cellular differentiation in acute lymphoblastic leukemia.
Acute lymphoblastic leukemia (ALL) is a heterogeneous entity that can be subcategorized on the basis of morphologic aspects, immunologic markers, membrane antigens, and enzymatic content of the blast forms. Subgroups corresponding to T-cell, pre-T-cell, pre-B-cell, and non-T-, non-B-lymphocyte derivations can be defined by immunologic markers, and the biologic differences are supported by the differential expression of membrane antigens and of nuclear, lysosomal, cytoplasmic, and membrane enzymes. These studies ease the diagnosis and characterization of ALL and enhance understanding of this disease.


Cut-off score of the Mattis Dementia Rating Scale for screening dementia in Parkinson's disease.
The prevalence of dementia in Parkinson's disease (PD) is close to 30%, and its incidence is 4 to 6 times higher than in age-matched general population. PD with dementia (PDD) is mainly characterized by a predominant and progressive frontal-subcortical impairment. The Mattis Dementia Rating Scale (MDRS) is a commonly used screening test that sensitively measures the degree of frontal-subcortical defects. Although the MDRS has been validated as a screening test of cognitive dysfunction in nondemented PD patients (PD-ND), its utility for screening dementia in PD is unknown. In order to validate the MDRS for diagnosis of PDD it was prospectively administered to 92 PD patients (57 PD-ND, 35 PDD) fulfilling UK-PDSBB criteria. Dementia was diagnosed according to DSM-IV-TR and a Clinical Dementia Rating (CDR) scale score >or=1. Univariate, logistic regression, and ROC curve analysis were carried out to measure the discriminative power of MDRS in PDD. Regression analysis showed MDRS total scores to independently differentiate PD-ND from PDD (P < 0.001). Age and education did not predict the presence of dementia. ROC curve analysis showed a cut-off score of <or=123 on the MDRS total scores to yield high sensitivity (92.65%), specificity (91.4%), positive and negative predictive values (PPV 83.3%, NPV 96.4%). A brief version of the MDRS obtained by the addition of the memory, initiation/perseveration, and conceptualization subscores yielded similar discriminant properties. The MDRS has an excellent discriminant ability to diagnose dementia in PD and provides an objective measure to distinguish PD-ND from PDD.