Overview of cancer vaccines: considerations for development.
Cancer immunotherapy has seen a tremendous number of failures and only few recent regulatory successes. This is a review dedicated to determine major regulatory and developmental issues around cancer immunotherapeutics. A three pillar approach should be used in setting a development path: discovery platforms and sufficient pool of validated tumor antigens, product development strategy enabling to bring the product closer to the patient and clinical development strategy accounting for competitive landscape, treatment paradigm, technical and commercial risks. Regulatory framework existing around cancer vaccines in the EU, US, Japan and some developing countries is outlined. In addition, the review covers some specific issues on the design and conduct of clinical trials with cancer vaccines.


Incidence and characteristics of non-accidental burns in children: A systematic review.
The estimated incidence of non-accidental burns varies between 1-25% in children. Distinguishing non-accidental burns from accidental burns can be very complicated but is of utmost importance for prevention of future injuries. Several studies concerning non-accidental burns have been published, however a clear overview is lacking. To conduct a systematic review of the existing literature to identify the incidence and characteristics of burns due to intentional causes and neglect. The protocol of this systematic review was prospectively registered in an international database (PROSPERO, National Institute for Health Research, York, United Kingdom). We searched literature in electronic databases published from 1948 until July 2018 written in English, Dutch, German and French. Two researchers screened, selected and graded the included articles, using standard methodology. We included primary studies of confirmed non-accidental burns in children. We excluded literature reviews, case-reports and unpublished data. We extracted data regarding demographics, burn characteristics, Child Protective Services (CPS) referral information and parent/household characteristics. 825 studies were screened, 17 were included. The incidence of non-accidental burns was pooled out of 10 studies and is 9.7%. Indicators raising a very high suspicion of intentional burns are deep partial thickness and full thickness burns, burns to the posterior trunk and burns caused by hot tap water. Indicators raising a high to moderate suspicion of an intentional cause are burns to buttocks, genital and legs, a younger age of the child, additional injuries such as cutaneous injuries/bruises and fractures. More commonly caused by accidents are burns to head, neck, anterior trunk, upper extremities and feet. Little data are available regarding burns as a result of neglect. Quality of studies was often low to moderate mostly due to a high heterogeneity. This review is mainly based on retrospective studies. From this review of the literature, the incidence of non-accidental burns in children was 9.7%. Indicators raising a very high suspicion of intentional burns are: location at the posterior trunk, deep partial thickness and full thickness burns and burns caused by hot tap water.


Coordination geometry of lead carboxylates - spectroscopic and crystallographic evidence.
Despite their versatility, only a few single-crystal X-ray structures of lead carboxylates exist, due to difficulties with solubility. In particular, the structures of long-chain metal carboxylates have not been reported. The lone electron pair in Pb(ii) can be stereochemically active or inactive, leading to two types of coordination geometries commonly referred to as hemidirected and holodirected structures, respectively. We report (13)C and (207)Pb solid-state NMR and infrared spectra for a series of lead carboxylates, ranging from lead hexanoate (C6) to lead hexadecanoate (C18). The lead carboxylates based on consistent NMR parameters can be divided in two groups, shorter-chain (C6, C7, and C8) and longer-chain (C9, C10, C11, C12, C14, C16, and C18) carboxylates. This dichotomy suggests two modes of packing in these solids, one for the short-chain lead carboxylates and one for long-chain lead carboxylates. The consistency of the (13)C and (207)Pb NMR parameters, as well as the IR data, in each group suggests that each motif represents a structure characteristic of each subgroup. We also report the single-crystal X-ray diffraction structure of lead nonanoate (C9), the first single-crystal structure to have been reported for the longer-chain subgroup. Taken together the evidence suggests that the coordination geometry of C6-C8 lead carboxylates is hemidirected, and that of C9-C14, C16 and C18 lead carboxylates is holodirected.


[Conservative treatment of chronic diseases of lower limb veins: major risks of poor patient compliance].
Presented herein are the results of the Russian part of the International Research Programme 'VEIN ACT' aimed at studying approaches to conservative treatment of chronic vein diseases in the Russian Federation, assessing its efficacy and safety, as well as monitoring the patient compliance. Also discussed are the regimen and results of conservative therapy, depending on patients' gender, age and body mass index, as well as the level of adherence to various methods of treatment in the cohorts concerned. High efficacy of conservative therapy in all patients was confirmed. However, the regimen of drug therapy needs to be adjusted depending on the disease severity, especially in patients of a more advanced age and those with obesity. The lowest patient compliance was observed in relation to compression treatment. The existing situation may be improved by be means of appropriate recommendations and a possible decrease of the level and degree of compression. This should of course be done carefully and attentively, with obligatorily taking into consideration the patients' age and body mass index.


Six3 promotes the formation of ectopic optic vesicle-like structures in mouse embryos.
A few years ago, three novel murine homeobox genes closely related to the Drosophila sine oculis (so) gene (Six1-3) were isolated and were all included in the Six/so gene family. Because of its early expression in the developing eye field, Six3 was initially thought to be the functional ortholog of the Drosophila so gene. This hypothesis was further supported by the demonstration that ectopic Six3 expression in medaka fish (Oryzias latipes) promotes the formation of ectopic lens and retina tissue. Here, we show that similar to Drosophila, where the eyeless/Pax6 gene regulates the eye-specific expression of so, Six3 expression in the murine lens placodal ectoderm is also controlled by Pax6. We also show that ectopic Six3 expression promotes the formation of ectopic optic vesicle-like structures in the hindbrain-midbrain region of developing mouse embryos.


Trends in the prevalence, risk and pregnancy outcome of multiple births with congenital anomaly: a registry-based study in 14 European countries 1984-2007.
To assess the public health consequences of the rise in multiple births with respect to congenital anomalies. Descriptive epidemiological analysis of data from population-based congenital anomaly registries. Fourteen European countries. A total of 5.4 million births 1984-2007, of which 3% were multiple births. Cases of congenital anomaly included live births, fetal deaths from 20 weeks of gestation and terminations of pregnancy for fetal anomaly. Prevalence rates per 10,000 births and relative risk of congenital anomaly in multiple versus singleton births (1984-2007); proportion prenatally diagnosed, proportion by pregnancy outcome (2000-07). Proportion of pairs where both co-twins were cases. Prevalence of congenital anomalies from multiple births increased from 5.9 (1984-87) to 10.7 per 10,000 births (2004-07). Relative risk of nonchromosomal anomaly in multiple births was 1.35 (95% CI 1.31-1.39), increasing over time, and of chromosomal anomalies was 0.72 (95% CI 0.65-0.80), decreasing over time. In 11.4% of affected twin pairs both babies had congenital anomalies (2000-07). The prenatal diagnosis rate was similar for multiple and singleton pregnancies. Cases from multiple pregnancies were less likely to be terminations of pregnancy for fetal anomaly, odds ratio 0.41 (95% CI 0.35-0.48) and more likely to be stillbirths and neonatal deaths. The increase in babies who are both from a multiple pregnancy and affected by a congenital anomaly has implications for prenatal and postnatal service provision. The contribution of assisted reproductive technologies to the increase in risk needs further research. The deficit of chromosomal anomalies among multiple births has relevance for prenatal risk counselling.


Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings.
Fifty-three patients underwent laser cordectomy for T1 glottic squamous cell carcinoma between January 1980 and December 1989--sixteen after having undergone unsuccessful radiation and thirty-seven who had no previous treatment. There was a 51% five-year cure rate in the irradiated group vs. 62% in the nonirradiated group. Extension of tumor to the anterior commissure resulted in a higher failure rate. Patients experienced an overall 5-year cure rate of 98% after surgical or radiation salvage of unsuccessful laser cordectomies. Six patients had preoperative and postoperative videostrobolaryngoscopy. The most common postoperative problem with voice was a breathiness that did not resolve in any of the patients. All patients had absent or moderately reduced amplitude and mucosal wave patterns and imcomplete glottic closure proportional to the amount of cordal tissue removed. Despite it seemingly poor results in carefully selected patients, laser cordectomy is still indicated without compromising the ultimate oncologic results. Advantages over radiation therapy or conservation laryngeal surgery include a short treatment time, requiring only an outpatient surgical procedure at the time of the initial diagnostic and/or staging laryngoscopy, and the avoidance of potential radiation side effects or surgical complications. However, patients should be advised the possibility of persistent postoperative breathy dysphonia, in addition to the possibility of further treatment to effect a long-term cure.


Exohedral functionalization vs. core expansion of siliconoids with Group 9 metals: catalytic activity in alkene isomerization.
Taking advantage of pendant tetrylene side-arms, stable unsaturated Si6 silicon clusters (siliconoids) with the benzpolarene motif (the energetic counterpart of benzene in silicon chemistry) are successfully employed as ligands towards Group 9 metals. The pronounced σ-donating properties of the tetrylene moieties allow for sequential oxidative addition and reductive elimination events without complete dissociation of the ligand at any stage. In this manner, either covalently linked or core-expanded metallasiliconoids are obtained. [Rh(CO)2Cl]2 inserts into an endohedral Si-Si bond of the silylene-functionalized hexasilabenzpolarene leading to an unprecedented coordination sphere of the Rh centre with five silicon atoms in the initial product, which is subsequentially converted to a simpler derivative under reconstruction of the Si6 benzpolarene motif. In the case of [Ir(cod)Cl]2 (cod = 1,5-cyclooctadiene) a similar Si-Si insertion leads to the contraction of the Si6 cluster core with concomitant transfer of a chlorine atom to a silicon vertex generating an exohedral chlorosilyl group. Metallasiliconoids are employed in the isomerization of terminal alkenes to 2-alkenes as a catalytic benchmark reaction, which proceeds with competitive selectivities and reaction rates in the case of iridium complexes.


Mapping national, regional and local prevalence of hypertension and diabetes in Ethiopia using geospatial analysis.
This study aimed to map the national, regional and local prevalence of hypertension and diabetes in Ethiopia. Nationwide cross-sectional survey in Ethiopia combined with georeferenced ecological level data from publicly available sources. 9801 participants aged between 15 and 69 years. Prevalence of hypertension and diabetes were collected using the WHO's STEPS survey approach. Bayesian model-based geostatistical techniques were used to estimate hypertension and diabetes prevalence at national, regional and pixel levels (1×1 km2) with corresponding 95% credible intervals (95% CrIs). The national prevalence was 19.2% (95% CI: 18.4 to 20.0) for hypertension and 2.8% (95% CI: 2.4 to 3.1) for diabetes. Substantial variation was observed in the prevalence of these diseases at subnational levels, with the highest prevalence of hypertension observed in Addis Ababa (30.6%) and diabetes in Somali region (8.7%). Spatial overlap of high hypertension and diabetes prevalence was observed in some regions such as the Southern Nations, Nationalities and People's region and Addis Ababa. Population density (number of people/km2) was positively associated with the prevalence of hypertension (β: 0.015; 95% CrI: 0.003-0.027) and diabetes (β: 0.046; 95% CrI: 0.020-0.069); whereas altitude in kilometres was negatively associated with the prevalence of diabetes (β: -0.374; 95% CrI: -0.711 to -0.044). Spatial clustering of hypertension and diabetes was observed at subnational and local levels in Ethiopia, which was significantly associated with population density and altitude. The variation at the subnational level illustrates the need to include environmental drivers in future NCDs burden estimation. Thus, targeted and integrated interventions in high-risk areas might reduce the burden of hypertension and diabetes in Ethiopia.


From healing the whole person: an argument for therapeutic touch as a complement to traditional medical practice.
The growing popularity and use of therapeutic touch (TT) is an issue that has generated controversy and concern within the medical community. While anecdotal and traditional scientific evidence suggest that TT would be an advantageous addition for clinics and hospitals to include in their armamentarium of complementary interventions within the realm of traditional medicine, TT has not become widely available in the U.S. One reason for the lack of availability may be the dearth of conclusive scientific support for TT's efficacy and, therefore, its inclusion in clinic and hospital treatment planning would give it the appearance of legitimate practice, which it may not yet deserve. Whether or not deserved, if TT were added to hospital and clinic treatment protocols without substantial scientific support, it would be thought to have the implicit support of the scientific community, at which point the question of its efficacy would be moot in the minds of many people; thus patients would utilize it, because they believe it works rather than because it works. Since TT has not yet been scientifically proven as per Western standards, leaders of the health care community are likely wary of lending support to TT at this time. If TT can be found to be a scientifically sound therapeutic technique, then it will be more readily accepted in the health care community. This paper reviews TT.


A Review of Sensing Systems and Their Need for Environmental Water Monitoring.
Water is a valuable natural resource and is needed to sustain human life. Water pollution significantly jeopardizes clean drinking water supplies, it is hazardous to human health, and it inhibits economic development. Well-designed sensors that can continuously monitor water quality during transport and identify contaminants in the watershed help effectively control pollution and thereby manage water resources. However, the commercially available sensors are expensive and require frequent maintenance. These limitations often make these sensors inadequate for continuous water monitoring applications. This review evaluates many sensors based on colorimetric, electrochemical, and optical sensors. Sensors suitable for estimating the amount of dissolved oxygen, nitrates, chlorine, and phosphates are presented. A review of recently developed high quality sensors for measuring the previously mentioned components of water is also presented. Future directions in this area of developing high quality sensors for water monitoring are discussed.


Derivation and characterization of replicate high- and low-alcohol preferring lines of mice and a high-drinking crossed HAP line.
Selectively breeding lines of mice and rats to differ in alcohol intake has proven useful for defining which traits correlate with high alcohol drinking behavior, as well as for creating animal models of alcoholism. This study reports the derivation of two novel sets of selected lines, High Alcohol Preferring (HAP) and Low Alcohol Preferring (LAP) replicate 2 and 3 lines. Mice were mass-selected using the same procedure as in the replicate 1 lines: using HS/Ibg as a progenitor, mice were selected for differences in 2-bottle choice intake of 10% alcohol during a 4-week testing period. In addition, another high-drinking line, the crossed HAP (cHAP) line was selectively bred from a progenitors that were a cross of replicate 1 (S27) × replicate 2 (S21) HAP lines. All lines were characterized for saccharin intake. Overall, the response to selection of the HAP and LAP replicate 2 and 3 lines was quite similar. As anticipated, following selection, the cHAP line drank more than either parent HAP line (consuming 26.0 g/kg per day of alcohol by S11), suggesting that this method of crossing replicate lines and selecting from that cross captures more alleles than any single selected line, as well as producing a line with exceptionally high voluntary alcohol intake. As expected, saccharin consumption was highly associated with alcohol consumption; data from 7 lines (HAP 1, 2, and 3, LAP 1, 2, and 3, and cHAP) indicated a genetic correlation between 10% alcohol and 0.32% saccharin intake of 0.91. Overall, these findings show the practicality of developing replicate lines divergent in alcohol preference, and validate a novel procedure for generating very high-drinking mouse populations.


The lived experience of multiple sclerosis: Patient insights to guide general practitioner care.
Multiple sclerosis (MS) is a neurodegenerative disease with symptoms that are varied and unpredictable, and although there are effective medications to treat some forms of MS, there is no cure. For many, an MS diagnosis means decades living with a chronic illness and disability. Providing medical and support care to people with MS can be a long and complex partnership between the patient and the general practitioner (GP). The aim of this article is to provide knowledge of the lived experience of MS and the factors leading to a reduced quality of life. Often alongside the considerable threats to physical health and neurological function that MS poses, there are also significant mental health burdens. This article uses lived experience to outline some of the crucial trigger points where support from the GP, and the wider general practice team, can have a significant impact on a positive path forward for the patient.


The Transcriptional Factor PPARαb Positively Regulates Elovl5 Elongase in Golden Pompano Trachinotus ovatus (Linnaeus 1758).
The nuclear peroxisome proliferator-activated receptors (PPARs) regulate the transcription of elongases of very long-chain fatty acids (Elovl), which are involved in polyunsaturated fatty acid (PUFA) biosynthesis in mammals. In the present study, we first characterized the function of Elovl5 elongase in Trachinotus ovatus. The functional study showed that ToElovl5 displayed high elongation activity toward C18 and C20 PUFA. To investigate whether PPARαb was a regulator of Elovl5, we also reported the sequence of T. ovatus PPARαb (ToPPARαb). The open reading frame (ORF) sequence encoded 469 amino acids possessing four typical characteristic domains, including an N-terminal hypervariable region, a DNA-binding domain (DBD), a flexible hinge domain and a ligand-binding domain (LBD). Thirdly, promoter activity experiments showed that the region from PGL3-basic-Elovl5-5 (-146 bp to +459 bp) was defined as the core promoter by progressive deletion mutation of Elovl5. Moreover, PPARαb overexpression led to a clear time-dependent enhancement of ToElovl5 promoter expression in HEK 293T cells. Fourth, the agonist of PPARαb prominently increased PPARαb and Elovl5 expression, while PPARαb depletion by RNAi or an inhibitor was correlated with a significant reduction of Elovl5 transcription in T. ovatus caudal fin cells (TOCF). In conclusion, the present study provides the first evidence of the positive regulation of Elovl5 transcription by PPARαb and contributes to a better understanding of the transcriptional mechanism of PPARαb in fish.


Positive results of endocervical curettage as an indication for conization of the cervix.
At University Hospital of Jacksonville (Fla) during the years 1981 through 1984, 37 patients had conization of the uterine cervix for the sole indication of dysplastic cells found on endocervical curettage. Eighteen of the 37 (48.7%) were found to have a more dysplastic lesion than that diagnosed by colposcopic biopsy. In two of the 37 (5.4%) a previously undiagnosed invasive cancer was found. We conclude that dysplastic cells found on endocervical curettage must be further evaluated with cold conization of the cervix.


The Taylor Family Institute at Washington University: Novel Treatments in Psychiatry.
Efforts to develop more effective treatments for psychiatric illnesses will require innovative approaches that address changes in brain networks underlying cognition, emotion and motivation, cardinal symptoms that cut across all psychiatric disorders. This effort will include new molecular entities that modulate neuronal excitability, synapses, cellular stress and inflammation. Other opportunities will come from repurposing existing treatments. This overview highlights current and future goals in treatment development in the Taylor Family Institute for Innovative Psychiatric Research at Washington University.


Effects of Tai Chi Exercise on glucose control, neuropathy scores, balance, and quality of life in patients with type 2 diabetes and neuropathy.
The aim of this study was to determine the effects of Tai Chi exercise on glucose control, neuropathy scores, balance, and quality of life in patients with type 2 diabetes and neuropathy. A pretest-posttest design with a nonequivalent control group was utilized to recruit 59 diabetic patients with neuropathy from an outpatient clinic of a university hospital. A standardized Tai Chi for diabetes program was provided, which comprised 1 hour of Tai Chi per session, twice a week for 12 weeks. Outcome variables were fasting blood glucose and glycosylated hemoglobin for glucose control, the Semmes-Weinstein 10-g monofilament examination scores and total symptom scores for neuropathy, single leg stance for balance, and the Korean version of the SF-36v2 for quality of life. Thirty-nine patients completed the posttest measures after the 12-week Tai Chi intervention, giving a 34% dropout rate. The mean age of the participants was 64 years, and they had been diagnosed with type 2 diabetes for more than 12 years. The status was significantly better for the participants in the Tai Chi group (n=20) than for their control (i.e., nonintervention) counterparts (n=19) in terms of total symptom scores, glucose control, balance, and quality of life. Tai Chi improved glucose control, balance, neuropathic symptoms, and some dimensions of quality of life in diabetic patients with neuropathy. Further studies with larger samples and long-term follow-up are needed to confirm the effects of Tai Chi on the management of diabetic neuropathy, which may have an impact on fall prevention in this population.


Doing the right thing and getting it right: professional perspectives in social work on supporting parents from gender diverse communities.
Despite significant shifts in legislative, political, cultural and social contexts, which have improved our understanding of diverse gender identities and family life, this remains under-explored within social work and social care. Trans and non-binary (TNB) parenting experiences are marginalized within mainstream professional practice and action is required to address these inequalities. This study explored the practices and meaning of 'parenting' and 'caring' for care professionals in families with parents with diverse gender identities in the UK. It aimed to capture a snapshot of the current state of practice knowledge and perceived practice challenges. A qualitative study design involving thematic analysis from detailed consultation with twenty-five relevant stakeholders in the proxy roles identified from a systematic review on what is known about trans parenting from the research evidence. The complexity of systems for supporting families creates barriers to change, with a lack of training and development in the knowledge and skills of the workforce. Intersecting these themes was a strong values framework and examples of best practice provided, which social workers can use to navigate, understand, and support TNB parents and their experiences, particularly at an individual level, as a means to effect change. Focusing on human rights, tailoring work to the specific needs of individuals and families, and affirming the diversity of family life requires professionals to take active responsibility and be more accountable in educating themselves and others on these rights. Professionals also need to reach out to the TNB community to include them in improving services as well as being active in their own organizations to ensure these are inclusive and responsive.


Endometriosis. The case for early, aggressive treatment.
While the debate rages on regarding how metabolic and immunologic changes fit into the pathophysiology of endometriosis, the clinician must nonetheless make decisions regarding treatment. This article examines the relevant literature, with particular emphasis on immunologic aspects, nonclassic, early and deep disease as well as data on progression, recurrence and effects of treatment, to propose innovations in the management of early-stage disease. All symptomatic early-stage disease should be treated aggressively--even after conservative surgical resection of all apparent endometriosis, adjunct medical treatment in the form of a gonadotropin-releasing hormone agonist should be strongly considered.


Network and State Specificity in Connectivity-Based Predictions of Individual Behavior.
Predicting individual behavior from brain functional connectivity (FC) patterns can contribute to our understanding of human brain functioning. This may apply in particular if predictions are based on features derived from circumscribed, a priori defined functional networks, which improves interpretability. Furthermore, some evidence suggests that task-based FC data may yield more successful predictions of behavior than resting-state FC data. Here, we comprehensively examined to what extent the correspondence of functional network priors and task states with behavioral target domains influences the predictability of individual performance in cognitive, social, and affective tasks. To this end, we used data from the Human Connectome Project for large-scale out-of-sample predictions of individual abilities in working memory (WM), theory-of-mind cognition (SOCIAL), and emotion processing (EMO) from FC of corresponding and non-corresponding states (WM/SOCIAL/EMO/resting-state) and networks (WM/SOCIAL/EMO/whole-brain connectome). Using root mean squared error and coefficient of determination to evaluate model fit revealed that predictive performance was rather poor overall. Predictions from whole-brain FC were slightly better than those from FC in task-specific networks, and a slight benefit of predictions based on FC from task versus resting state was observed for performance in the WM domain. Beyond that, we did not find any significant effects of a correspondence of network, task state, and performance domains. Together, these results suggest that multivariate FC patterns during both task and resting states contain rather little information on individual performance levels, calling for a reconsideration of how the brain mediates individual differences in mental abilities.


The inner membrane protein YhdP modulates the rate of anterograde phospholipid flow in Escherichia coli.
The outer membrane (OM) of Gram-negative bacteria is a selective permeability barrier that allows uptake of nutrients while simultaneously protecting the cell from harmful compounds. The basic pathways and molecular machinery responsible for transporting lipopolysaccharides (LPS), lipoproteins, and β-barrel proteins to the OM have been identified, but very little is known about phospholipid (PL) transport. To identify genes capable of affecting PL transport, we screened for genetic interactions with mlaA*, a mutant in which anterograde PL transport causes the inner membrane (IM) to shrink and eventually rupture; characterization of mlaA*-mediated lysis suggested that PL transport can occur via a high-flux diffusive flow mechanism. We found that YhdP, an IM protein involved in maintaining the OM permeability barrier, modulates the rate of PL transport during mlaA*-mediated lysis. Deletion of yhdP from mlaA* reduced the rate of IM transport to the OM by 50%, slowing shrinkage of the IM and delaying lysis. As a result, the weakened OM of ∆yhdP cells was further compromised and ruptured before the IM during mlaA*-mediated death. These findings demonstrate the existence of a high-flux diffusive pathway for PL flow in Escherichia coli that is modulated by YhdP.


Family physicians supporting patients with palliative care needs within the patient medical home in the community: an appreciative inquiry study.
Canadians want to live and die in their home communities. Unfortunately, Canada has the highest proportion of deaths in acute care facilities as compared with other developed nations. This study aims to identify the essential components required to best support patients and families with palliative care needs in their communities to inform system changes and empower family physicians (FPs) in providing community-based palliative care for patients. Appreciative inquiry (AI) methodology with individual interviews. Interview transcripts were analysed iteratively for emerging themes and used to develop 'possibility statements' to frame discussion in subsequent focus groups. A conceptual framework emerged to describe the 'destiny' state as per AI methods. FPs, palliative home care providers, patients and bereaved caregivers were recruited in the urban and surrounding rural health authority zones of Calgary, AB, Canada. 9 females and 9 males FPs (range of practice years 2-42) in interviews; 8 bereaved caregivers, 1 patient, 26 palliative home care team members in focus groups. Interviews and focus groups were recorded digitally and transcribed with consent. The identified themes that transcended all three groups created the foundation for the conceptual framework. Enhanced communication and fostering team relationships between all care providers with the focus on the patient and caregivers was the cornerstone concept. The FP/patient relationship must be protected and encouraged by all care providers, while more system flexibility is needed to respond more effectively to patients. These concepts must exist in the context that patients and caregivers need more education regarding the benefits of palliative care, while increasing public discourse about mortality. Key areas were identified for how the patient's team can work together effectively to improve the patient and caregiver palliative care journey in the community with the cornerstone element of building on the trusting FP-patient longitudinal relationship.


Xenogeneic monoclonal antibodies to cell surface antigens of equine lymphocytes.
Monoclonal antibodies to equine lymphocyte antigens were produced, using normal peripheral blood lymphocytes as the immunogen and standard hybridoma techniques. Antibody producing hybridomas were detected by a solid-phase enzyme-linked immunosorbent assay. Antibodies produced by 6 cloned hybrids were characterized further by microlymphocytotoxicity, indirect immunofluorescence, and agglutination assays on peripheral blood lymphocytes, platelets, and erythrocytes. Reaction patterns on leukocytes indicated that these antibodies may recognize at least 3 different cell-surface antigens: (1) an antigen present on most peripheral blood lymphocytes and on platelets, (2) an antigen present on most peripheral blood lymphocytes, but absent from platelets, and (3) an antigen expressed by a major subpopulation of lymphocytes and also present on platelets. This last antigen is polymorphic and is expressed on the lymphocytes of approximately 75% of horses. The distribution of this polymorphic antigen did not correlate with the antigen distribution of any of the defined antigens of the equine major histocompatibility system. None of the 6 monoclonal antibodies reacted with antigens expressed on erythrocytes. These results indicate that monoclonal antibodies may be useful for the identification and characterization of various leukocyte antigens in the horse.


Cold-water immersion (cryotherapy) for preventing and treating muscle soreness after exercise.
Many strategies are in use with the intention of preventing or minimising delayed onset muscle soreness and fatigue after exercise. Cold-water immersion, in water temperatures of less than 15°C, is currently one of the most popular interventional strategies used after exercise. To determine the effects of cold-water immersion in the management of muscle soreness after exercise. In February 2010, we searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library (2010, Issue 1), MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health (CINAHL), British Nursing Index and archive (BNI), and the Physiotherapy Evidence Database (PEDro). We also searched the reference lists of articles, handsearched journals and conference proceedings and contacted experts.In November 2011, we updated the searches of CENTRAL (2011, Issue 4), MEDLINE (up to November Week 3 2011), EMBASE (to 2011 Week 46) and CINAHL (to 28 November 2011) to check for more recent publications. Randomised and quasi-randomised trials comparing the effect of using cold-water immersion after exercise with: passive intervention (rest/no intervention), contrast immersion, warm-water immersion, active recovery, compression, or a different duration/dosage of cold-water immersion. Primary outcomes were pain (muscle soreness) or tenderness (pain on palpation), and subjective recovery (return to previous activities without signs or symptoms). Three authors independently evaluated study quality and extracted data. Some of the data were obtained following author correspondence or extracted from graphs in the trial reports. Where possible, data were pooled using the fixed-effect model. Seventeen small trials were included, involving a total of 366 participants. Study quality was low. The temperature, duration and frequency of cold-water immersion varied between the different trials as did the exercises and settings. The majority of studies failed to report active surveillance of pre-defined adverse events.Fourteen studies compared cold-water immersion with passive intervention. Pooled results for muscle soreness showed statistically significant effects in favour of cold-water immersion after exercise at 24 hour (standardised mean difference (SMD) -0.55, 95% CI -0.84 to -0.27; 10 trials), 48 hour (SMD -0.66, 95% CI -0.97 to -0.35; 8 trials), 72 hour (SMD -0.93; 95% CI -1.36 to -0.51; 4 trials) and 96 hour (SMD -0.58; 95% CI -1.00 to -0.16; 5 trials) follow-ups. These results were heterogeneous. Exploratory subgroup analyses showed that studies using cross-over designs or running based exercises showed significantly larger effects in favour of cold-water immersion. Pooled results from two studies found cold-water immersion groups had significantly lower ratings of fatigue (MD -1.70; 95% CI -2.49 to -0.90; 10 units scale, best to worst), and potentially improved ratings of physical recovery (MD 0.97; 95% CI -0.10 to 2.05; 10 units scale, worst to best) immediately after the end of cold-water immersion.Five studies compared cold-water with contrast immersion. Pooled data for pain showed no evidence of differences between the two groups at four follow-up times (immediately, 24, 48 and 72 hours after treatment). Similar findings for pooled analyses at 24, 48 and 72 hour follow-ups applied to the four studies comparing cold-water with warm-water immersion. Single trials only compared cold-water immersion with respectively active recovery, compression and a second dose of cold-water immersion at 24 hours. There was some evidence that cold-water immersion reduces delayed onset muscle soreness after exercise compared with passive interventions involving rest or no intervention. There was insufficient evidence to conclude on other outcomes or for other comparisons. The majority of trials did not undertake active surveillance of pre-defined adverse events. High quality, well reported research in this area is required.


Synthesis/degradation ratio mass spectrometry for measuring relative dynamic protein turnover.
One of the major unanswered questions in quantitative proteomics is that of dynamic protein turnover in the cell. Here we present a new approach to quantitative proteomics that measures the relative dynamic turnover of proteins in cellular systems. In this approach, termed synthesis/degradation ratio mass spectrometry, stable isotope labeling is employed to calculate a relative synthesis/degradation ratio that reflects the relative rate at which 13C is incorporated into individual proteins in the cell. This synthesis/degradation ratio calculation is based on a Poisson distribution model that is designed to support high-throughput analysis. Protein separation and analysis is accomplished by utilizing one-dimensional SDS-PAGE gel electrophoresis followed by cutting the gel into a series of bands for in-gel digestion. The resulting peptide mixtures are analyzed via solid-phase MALDI LC-MS and LC-MS/MS using a tandem time-of-flight mass spectrometer. A portion of the soluble protein fraction from an E. coli K-12 strain was analyzed with synthesis/degradation ratios varying from approximately 0.1 to 4.4 for a variety of different proteins. Unlike other quantitative techniques, synthesis/degradation ratio mass spectrometry requires only a single cell culture to obtain useful biological information about the processes occurring inside a cell. This technique is highly amenable to shotgun proteomics-based approaches and thus should allow relative turnover measurements for whole proteomes in the future.


Compensatory kidney growth in estrogen receptor-alpha null mice.
Females are relatively protected in many progressive kidney diseases. Processes of kidney scarring and growth are intricately linked, and female kidneys are smaller than male kidneys. To better understand links between sex, growth, and the kidney, we examined compensatory kidney growth (CKG) after uninephrectomy (Unx) in wild-type and estrogen receptor-alpha null mice (ERKO). Mice (10 wk old) underwent Unx or sham procedure, with removal of all remaining kidney(s) 48 h later. Studies included kidney weight, renal content of protein, DNA, and insulin-like growth factor-I (IGF-I), serum IGF-I, mean glomerular area, and immunostaining for proliferating cell nuclear antigen (PCNA). Sham Unx produced no differences between left and right kidneys. Unx altered kidney weight, glomerular area, DNA content, IGF-I content, and PCNA regardless of sex or genotype. Females showed greater increases in kidney weight (26 vs. 19%) and glomerular area (73 vs. 51%) than males. Differences in kidney weight were restricted to wild-type females (32% increase); ERKO females showed an increase in kidney weight similar to males (19%). Genotype did not influence glomerular growth in this model. Both male and female mice exhibit hyperplastic growth 48 h after Unx, with more pronounced enlargement in females. Lack of estrogen receptor-alpha is associated with reduced CKG in females, probably via suppression of proliferation. ERKO mice did not demonstrate any alterations in compensatory glomerular enlargement. Kidney IGF-I content doubled after Unx, regardless of sex or genotype, implicating other mechanisms with regard to these findings.


Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery: A multicenter cohort analysis from the FRANCOGYN study group.
The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery. Data from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival. The median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16-3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01-2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC. In this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.


The Molecular Basis of Acinetobacter baumannii Cadmium Toxicity and Resistance.
Acinetobacter species are ubiquitous Gram-negative bacteria that can be found in water, in soil, and as commensals of the human skin. The successful inhabitation of Acinetobacter species in diverse environments is primarily attributable to the expression of an arsenal of stress resistance determinants, which includes an extensive repertoire of metal ion efflux systems. Metal ion homeostasis in the hospital pathogen Acinetobacter baumannii contributes to pathogenesis; however, insights into its metal ion transporters for environmental persistence are lacking. Here, we studied the impact of cadmium stress on A. baumannii. Our functional genomics and independent mutant analyses revealed a primary role for CzcE, a member of the cation diffusion facilitator (CDF) superfamily, in resisting cadmium stress. We also show that the CzcCBA heavy metal efflux system contributes to cadmium efflux. Collectively, these systems provide A. baumannii with a comprehensive cadmium translocation pathway from the cytoplasm to the periplasm and subsequently the extracellular space. Furthermore, analysis of the A. baumannii metallome under cadmium stress showed zinc depletion, as well as copper enrichment, both of which are likely to influence cellular fitness. Overall, this work provides new knowledge on the role of a broad arsenal of membrane transporters in A. baumannii metal ion homeostasis. IMPORTANCE Cadmium toxicity is a widespread problem, yet the interaction of this heavy metal with biological systems is poorly understood. Some microbes have evolved traits to proactively counteract cadmium toxicity, including Acinetobacter baumannii, which is notorious for persisting in harsh environments. Here, we show that A. baumannii utilizes a dedicated cadmium efflux protein in concert with a system that is primarily attuned to zinc efflux to efficiently overcome cadmium stress. The molecular characterization of A. baumannii under cadmium stress revealed how active cadmium efflux plays a key role in preventing the dysregulation of bacterial metal ion homeostasis, which appeared to be a primary means by which cadmium exerts toxicity upon the bacterium.


Integrating management of physician groups and hospitals.
This chapter discusses the management challenges facing hospitals as they enter into formal organizational and economic linkages with physician organizations. Managing physician organizations does not simply mean controlling physicians through employment arrangements, but rather providing an organizational structure through which physicians can work together and with the hospital toward a common goal of creating a high-quality, cost-effective system of patient care. Integration of the management approaches required to run hospitals and physician groups successfully represents a significant challenge. Meeting this challenge is key to creating an organization that will be able to truly manage care.


[Cerebral metastases of gynecological origin].
A few cases of brain metastasis from gynecological cancer have been reported. This tumor usually dissaminates via the blood stream, normally through surface implantation or lymphatic spread. We report four cases of brain metastases from gynecological cancer (2 from ovarian cancer and 2 from endometrial cancer). Several months later, three patients developed brain metastases without any other location elsewhere. For the other patient, brain metastasis was the first sign of her malignant disease. In brain metastases from gynecological cancer, treatment should consist in surgical resection, radiation therapy and chemotherapy.


Decreasing photobleaching by silver island films: application to muscle.
Recently it has become possible to study interactions between proteins at the level of single molecules. This requires collecting data from an extremely small volume, small enough to contain one molecule-typically of the order of attoliters (10(-18) L). Collection of data from such a small volume with sufficiently high signal-to-noise ratio requires that the rate of photon detection per molecule be high. This calls for a large illuminating light flux, which in turn leads to rapid photobleaching of the fluorophores that are labeling the proteins. To decrease photobleaching, we measured fluorescence from a sample placed on coverslips coated with silver island films (SIF). SIF reduce photobleaching because they enhance fluorescence brightness and significantly decrease fluorescence lifetime. Increase in the brightness effectively decreases photobleaching because illumination can be attenuated to obtain the same fluorescence intensity. Decrease of lifetime decreases photobleaching because short lifetime minimizes the probability of oxygen attack while the fluorophore is in the excited state. The decrease of photobleaching was demonstrated in skeletal muscle. Myofibrils were labeled lightly with rhodamine-phalloidin, placed on coverslips coated with SIF, illuminated by total internal reflection, and observed through a confocal aperture. We show that SIF causes the intensity of phalloidin fluorescence to increase 4-5 fold and its fluorescence lifetime to decrease on average 23-fold. As a consequence, the rate of photobleaching of four or five molecules of actin of a myofibril on Olympus coverslips coated with SIF decreased at least 30-fold in comparison with photobleaching on an uncoated coverslip. Significant decrease of photobleaching makes the measurement of signal from a single cross-bridge of contracting muscle feasible.


Human masseter muscle fibers from the elderly express less neonatal Myosin than those of young adults.
In contrast to limb muscles where neonatal myosin (MyHC-neo) is present only shortly after birth, adult masseter muscles contain a substantial portion of MyHC-neo, which is coexpressed with mature MyHC isoforms. Changes in the numerical and area proportion of muscle fibers containing MyHC-neo in masseter muscle with aging could be expected, based on previously reported findings that (i) developmental MyHC-containing muscle fibers exhibit lower shortening velocities compared to fibers with exclusively fast MyHC isoforms and (ii) transformation toward faster phenotype occurs in elderly compared to young masseter muscle. In this study, we detected MyHC isoforms in the anterior superficial part of the human masseter muscle in a sufficiently large sample of young, middle-aged, and elderly subjects to reveal age-related changes in the coexpression of MyHC-neo with adult MyHC isoforms. MyHC isoforms were visualized with immunoperoxidase method and the results were presented by (i) the area proportion of fibers containing particular MyHC isoforms and (ii) the numerical proportion of fiber types defined by MyHC-1, -2a, -2x, and -neonatal isoform expression from a successive transverse sections. We found a lower numerical and area proportion of fibers expressing MyHC-neo as well as a lower area proportion of fibers containing MyHC-1 in elderly than in young subjects. We conclude that the diminished expression of MyHC-neo with age could point to a lower regeneration capacity of masseter muscle in the elderly.


The regulation of AβPP expression by RNA-binding proteins.
Amyloid β-protein precursor (AβPP) is cleaved by β- and γ-secretases to liberate amyloid beta (Aβ), the predominant protein found in the senile plaques associated with Alzheimer's disease (AD) and Down syndrome (Masters et al., 1985). Intense investigation by the scientific community has centered on understanding the molecular pathways that underlie the production and accumulation of Aβ Therapeutics that reduce the levels of this tenacious, plaque-promoting peptide may reduce the ongoing neural dysfunction and neuronal degeneration that occurs so profoundly in AD. AβPP and Aβ production are highly complex and involve still to be elucidated combinations of transcriptional, post-transcriptional, translational and post-translational events that mediate the production, processing and clearance of these proteins. Research in our laboratory for the past two decades has focused on the role of RNA binding proteins (RBPs) in mediating the post-transcriptional as well as translational regulation of APP messenger RNA (mRNA). This review article summarizes our findings, as well as those from other laboratories, describing the identification of regulatory RBPs, where and under what conditions they interact with APP mRNA and how those interactions control AβPP and Aβ synthesis.


Preferential growth of mammary tumors in intact mammary fatpads.
Four transplantable tumors, three (66, 410, and 168cl) isolated from a spontaneously occurring strain BALB/cfC3H mammary tumor and one (D2) arising from a BALB/c hyperplastic alveolar nodule were found to grow better in mammary fatpads than at s.c. sites. Furthermore, tumor growth was better (p less than 0.05) in intact mammary glands than in cleared mammary fatpads for the D2, 410, and 66 tumors (168cl was not tested). The role of immunity in these differences was investigated using the highly immunogenic 410 tumors. Tumor 410 induced equally effective immunity to subsequent challenge whether it was implanted s.c. or in intact fatpads. Furthermore, in immunized animals, Tumor 410 was rejected equally well when the challenge site was intact fatpad as when s.c. Similarly, Tumor 410 induced immunity after implantation into cleared fatpads and, in immunized animals, was rejected when the challenge site was the cleared fatpad. We thus found no evidence that the mammary fatpad is immunologically privileged, as compared to the s.c. site, with respect to tumor transplantation antigens.


Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation.
Partial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset of many diseases of aging. However, the delivery of transgenes and potential risk of teratoma formation present challenges for in vivo applications. Recent advances include the use of cocktails of compounds to reprogram somatic cells, but the characteristics and mechanisms of partial cellular reprogramming by chemicals remain unclear. Here, we report a multi-omics characterization of partial chemical reprogramming in fibroblasts from young and aged mice. We measured the effects of partial chemical reprogramming on the epigenome, transcriptome, proteome, phosphoproteome, and metabolome. At the transcriptome, proteome, and phosphoproteome levels, we saw widescale changes induced by this treatment, with the most notable signature being an upregulation of mitochondrial oxidative phosphorylation. Furthermore, at the metabolome level, we observed a reduction in the accumulation of aging-related metabolites. Using both transcriptomic and epigenetic clock-based analyses, we show that partial chemical reprogramming reduces the biological age of mouse fibroblasts. We demonstrate that these changes have functional impacts, as evidenced by changes in cellular respiration and mitochondrial membrane potential. Taken together, these results illuminate the potential for chemical reprogramming reagents to rejuvenate aged biological systems and warrant further investigation into adapting these approaches for in vivo age reversal.


[Biological aspects of Bemisia tabaci (Genn.) B biotype (Hemiptera: Aleyrodidae) on six bean genotypes].
The silverleaf whitefly is one of the most harmful pests that attack bean crops, mainly for extracting large quantities of phloem sap and transmitting the bean golden mosaic virus. Resistant germoplasm plants can be an important method for controlling this pest. The biological aspects of Bemisia tabaci B biotype on bean (Phaseolus vulgaris) genotypes were evaluated. The tests were conducted under laboratory conditions, with the following genotypes: Arc 1, Arc 3s, Arc 5s, G13028, G11056 and Porrillo 70. The bean plants in a stage IV-1 were infested during one day with silverleaf whiteflies. Afterwards the eggs and nymphs were observed until adult emergence. Longevity and fecundity of emerged insects were also evaluated. The longest development time occurred for nymphs fed on Arc 3s genotype (26.5 days), following by G11056 (25.9 days) and G13028 (25.3 days). The development period was 5.5 days longer in Arc 3s when compared with Porrillo 70. Also, the wild genotypes Arc 3s and G11056 showed higher mortality rates (94.7% and 83.1%, respectively), which may suggest antibiosis and/or feeding nonpreference resistance type. For this reason, although longevity and fecundity were not influenced when the whitefly fed on resistant genotypes (Arc 3s, G11056, G13028 and Arc 5s), those genotypes can be used for bean breeding program towards B. tabaci B biotype.


Occult thyroid carcinoma: a rare case report and review of literature.
Occult thyroid carcinoma is very common in the clinic and is generally divided into four groups. Here, we proposed two types of occult thyroid carcinoma as the fifth group. The first type was locoregional lymph node metastases from thyroid carcinoma, and the second type was distant organ metastases from thyroid carcinoma. The unique aspect of the fifth group was that the primary carcinoma of the fifth group was not finally found by pathological examination. To better understand the fifth group, we reported a typical case. Furthermore, we discussed the diagnostic criteria and procedures and the management of the fifth group of occult thyroid carcinoma.


The Effect of the Crow Hop on Elbow Stress During an Interval Throwing Program.
Postoperative rehabilitation protocols after ulnar collateral ligament (UCL) reconstruction typically involve a structured interval throwing program. In an effort to minimize torque placed on the UCL, athletes are often instructed to throw with a crow hop, even at short throwing distances. However, the effect of the crow hop on medial elbow stress is unknown. The purpose was to determine whether elbow stress differs with and without a crow hop across the throwing distances of a typical interval throwing program. We hypothesized that crow hop throws would generate lower torque on the elbow than standing throws at each distance of the interval throwing program. Controlled laboratory study. Healthy high school and collegiate pitchers and position players were recruited from the surrounding area. Each player was outfitted with a wearable athletic sleeve and device that recorded elbow torque (Newton-meters), arm slot (degrees), arm speed (revolutions per minute), and shoulder rotation (degrees). Ball velocity (miles per hour) was measured using a radar gun. Players were instructed to perform 3 crow hop throws and 3 standing throws at distances of 30, 45, 60, 90, 120, 150, and 180 feet. A repeated measures analysis of variance was used to compare ball velocity, elbow torque, arm slot, arm speed, and shoulder rotation between crow hop and standing throws at each throwing distance. Twenty athletes participated in this study (average age, 17.8 years; range, 15-25 years). The average medial elbow torque increased at each distance for both crow hop and standing throws at distances of 30, 45, 60, and 90 feet (P < .05), after which there were no significant increases in elbow torque (P > .05). The average torque was higher for crow hop throws than standing throws at distances of 30 feet (13.9 N·m vs 12.0 N·m; P = .002), 45 feet (21.8 N·m vs 19.3 N·m; P = .005), and 60 feet (28.0 N·m vs 24.5 N·m; P = .02). Crow hop throws generated greater medial elbow torque than standing throws at distances up to 60 feet; however, there were no differences in elbow torque at distances greater than 60 feet between the 2 throw types. For both crow hop and standing throws, elbow stress increased at each distance interval up to 90 feet before plateauing at distances greater than 90 feet. The crow hop throwing technique does not reduce medial elbow stress during a simulated interval throwing program, and it may actually increase torque at shorter throwing distances. The results of our study indicate that it would be prudent for players to initially perform standing throws at shorter distances and only later be allowed to employ a natural crow hop at greater distances to minimize torque placed on the medial elbow during UCL rehabilitation protocols.


The tooth wear evaluation system: a modular clinical guideline for the diagnosis and management planning of worn dentitions.
Tooth wear is a multifactorial condition, leading to the loss of dental hard tissues, viz. enamel and dentine. Tooth wear can be divided into the subtypes mechanical wear (attrition and abrasion) and chemical wear (erosion). Because of its multifactorial aetiology, tooth wear can manifest itself in many different representations, and therefore, it can be difficult to diagnose and manage the condition. A systematic approach is a sine qua non. In the below-described tooth wear evaluation system (TWES), all necessary tools for a clinical guideline are present in different modules. This allows the dental clinician, in a general practitioner setting as well as in a referral practice setting, to perform a state-of-the-art diagnostic process. To avoid the risk of a too cumbersome usage, the dental clinician can select only those modules that are appropriate for a given setting. The modules match with each other, which is indispensable and essential when different modules of the TWES are compared. With the TWES, it is possible to recognise the problem (qualifying), to grade its severity (quantifying), to diagnose the likely causes and to monitor (the progress of) the condition. In addition, a proposal for the classification of tooth wear is made. Further, it is possible to determine when to start a treatment, to make the decision which kind of treatment to apply and to estimate the level of difficulty of a restorative treatment.


Nucleotide sequence of the genes III, VI and I of bacteriophage M13.
A DNA region of 2750 base pairs encompassing the genes III, VI and I of bacteriophage M13 has been sequenced by the Maxam-Gilbert procedure. By establishing the nucleotide changes introduced by several amber mutations, the coding region and the regulatory signals of each gene have been deduced. The genes appear to span 1275 base pairs (gene III; mol.wt. 44,748) 339 base pairs (gene VI; mol.wt. 12,264) and 1047 base pairs (gene I; mol.wt. 39,500). Their separating non-codogenic regions are extremely short, namely two and one base pair, respectively. The C-terminal end of gene I, however, intrudes 23 nucleotides into gene IV. From the nucleotide sequence it appears that the minor capsid protein of the phage, which is encoded by gene III, is synthesized in a precursor form containing 18 extra amino acids at its N-terminal end. Furthermore, in this capsid protein two clusters of a fourfold repeat of the sequence Glu-Gly-Gly-Gly-Ser are apparent. Gene VI appears to code for a small, extremely hydrophobic polypeptide. Its total hydrophobic amino acids content of 51% suggests that this protein can only function in the host cell membrane.


Voluntary Hydration with Skimmed Lactose-Free Milk during Exercise in the Heat: Exploring Effectiveness and Tolerance.
Replacement of fluid losses (dehydration) during sports activities in the heat has been investigated with different beverages. Bovine milk has been recommended for post-exercise rehydration, but its use during exercise may provoke gastrointestinal disorders. This study compared voluntary fluid intake, hydration, and incidence and severity of gastrointestinal (GI) disorders during exercise in the heat under three conditions: no drink (ND), water (W), and skimmed lactose-free milk (SM). Sixteen physically active university students exercised at 32 °C and 70% RH for 90 min at 60-75% HRmax while drinking W or SM ad libitum, or ND assigned at random. A questionnaire explored possible GI disorders. Ad libitum intake was higher (p < 0.05) for water (1206.2 mL) than milk (918.8 mL). Dehydration showed significant differences for SM versus W and ND (W = 0.28% BM; SM = -0.07% BM; ND = 1.38% BM, p < 0.05). Urine volume was significantly higher (p < 0.05) in the W condition (W = 220.4 mL; SM = 81.3 mL; ND = 86.1 mL). Thick saliva, belching, and abdominal pain were higher for SM, but scores were low. Skimmed lactose-free milk is a suitable, effective alternative to be consumed as a hydration beverage during moderate-intensity cycling in the heat for 90 min.


Evaluation of field epidemiology specialist training program based on the satisfaction and the changes of educational needs.
To evaluate the learning achievement and satisfaction levels for the Field Epidemiology Specialist Training Program (FESTP), on infectious disease control between March 19 and October 31, 2002. The FESTP was designed as a set of 84 hours curricula including lectures, discussions, self-studies, and field practicals, and organized both centrally and locally by the Division of Communicable Disease Control of the National Institute of Health and 11 universities. Before and after the program, a questionnaire survey on the educational need (49 items) and satisfaction (15 items) was conducted on 484 trainees, who were responsible for communicable disease control and immunization at 242 regional health centers. The data were analyzed with paired t-tests for comparison of the educational needs between the pre and post scores. The average score for satisfaction was 3.06 out of 5.0; with relatively higher scores for sincerity (4.10) and professionalism (4.01) of the tutors, adequacy (3.54) and clearness (3.51) of the evaluation criteria, usefulness (3.54) and fitness (3.52) of the contents, but with relatively lower satisfaction for schedule (2.96) and self-studies (2.91). The average for requirement for education improved, as shown by the decrease from 2.72 to 2.22 (p< .0001) with the biggest decrease in the outbreak investigation from 2.60 to 2.08. The FESTP was evaluated as being effective, the trainees showed moderate satisfaction and decrease educational needs. However, the actual schedules and self-studies should be rearranged to improve the satisfaction level.


Postcesarean epidural morphine: a dose-response study.
The purpose of this study was to describe the dose-response relationship of epidural morphine for postcesarean analgesia for quality of analgesia and relation to the side effects of pruritus, nausea, and vomiting. Sixty term parturients undergoing nonurgent cesarean delivery were enrolled and randomized to receive a single dose of epidural morphine after delivery (0,1.25, 2.5, 3.75, or 5 mg). A patient-controlled analgesia (PCA) device provided free access to additional analgesics. PCA morphine use and the incidence and severity of side effects were recorded for 24 h. Data were analyzed with analysis of variance, Student's t-tests, and chi(2) analysis. Nonlinear regression was used to describe a dose-response curve. PCA use differed significantly among groups (P < 0.001); PCA use was significantly greater in Group 0 mg than Groups 2.5, 3.75, and 5 mg (P < 0.05). PCA use was also significantly greater in Group 1.25 mg than Groups 3.75 and 5 mg (P < 0.05). Pruritus scores were significantly higher in all groups given epidural morphine than the control group (0 mg) (P < 0.05), but did not differ among the treatment groups (1.25-5 mg), although pruritus scores were significantly higher in treatment groups than in the control (P < 0. 05). No relation was found between epidural morphine dose and incidence or severity of nausea and vomiting. We concluded that, for optimal analgesia, augmentation of epidural morphine with systemic analgesics or other epidural medications may be necessary. Quality of analgesia increases as the dose of epidural morphine increases to at least 3.75 mg; increasing the dose further to 5 mg did not improve analgesia. Side effects were not dose related. For optimal analgesia, augmentation of epidural morphine with systemic analgesics or other epidural medications may be necessary.


Field experimental evidence for diffuse competition among Southwestern riparian birds.
In a 6-yr study of 70 generally insectivorous bird species in Arizona riparian woodlands, abundances of cavity-nesting species increased on 50 experimental plots compared with 49 control plots, following addition of artificial nest boxes. Open-nesting birds increased in abundance on control plots during the study but avoided experimental plots relative to control plots after box addition. Multivariate analysis revealed that a negative response of open nesters to the experiment was widespread among a large and ecologically diverse group of species. Results of this field experiment suggest that communitywide (diffuse) competition was an important factor influencing the distribution and abundance of birds in these riparian ecosystems.


Vaccination coverage among children aged 13 to 59 months in Buenos Aires, Argentina, 2002.
To estimate antigen-specific and series-complete vaccination coverage among children aged 13 to 59 months in Buenos Aires; to compare the results of a community-based household survey with coverage rates obtained from administrative records; and to identify risk factors for incomplete vaccination. Census tracts in Buenos Aires were surveyed systematically in March and April, 2002. Three children aged 13 to 24 months and 25 to 59 months were surveyed per block in each census tract. Written documentation of vaccination was required. Risk factors associated with incomplete vaccination were identified with univariate analysis and multivariate logistic regression. A total of 1391 children were surveyed. Antigen-specific coverage ranged from 69.4% (95% CI 66.7%-72%) for Haemophilus influenzae type b vaccination to 99% (95% CI 98.4%-99.6%) for BCG vaccination. Except for measles, coverage estimates found in the survey did not differ substantially from those obtained from city health authority records. Multivariate logistic regression analysis showed child's age (P < 0.001) and vaccination provider (public or private) (P = 0.001) to be risk factors associated with incomplete vaccination. Not being the first child (P < 0.001) was associated with incomplete coverage under the long-standing program. Living in the Northern zone of the city (P = 0.001), being uninsured (P = 0.02), and lower educational level of the primary caregiver (P = 0.04) were risk factors associated with incomplete coverage under the current vaccination program. Although coverage rates for some vaccines were high, complete vaccination coverage remains low among children aged 13 to 59 months in Buenos Aires. Increasing coverage will require better access to vaccination, particularly in sections of the community with risk factors.


Reversing urban decay: brownfield redevelopment and environmental health.
While the United States government concentrates more of its political and financial resources on fighting terrorism, the continuing decay of older cities and industrial suburbs has fallen far down on the national political priority agenda. An exception is the redevelopment of so-called brownfields, which are abandoned, idled, or underutilized factories, railroad yards, bus stations, garages, electricity-generating stations, and other commercial facilities. A modest national government program to identify, clean up, and redevelop brownfields into job fields began during the administration of Bill Clinton and has continued into the George W. Bush administration (Powers et al. 2000; Simons 1998; Van Horn et al. 1999). The political reasons are apparent: Developing brownfields is a politically acceptable method of stimulating private enterprise, local government, and community groups into building new businesses, housing, and community facilities. Also, brownfields projects have a beginning and an end; the national government does not have an indefinite responsibility. In contrast, social assistance programs that grew during the 1960s and proliferated for more than three decades have been politically portrayed by some as give-away programs that build dependency with no ending. Whether this characterization of social programs is morally or empirically justified, the reality is that in today's political environment brownfields redevelopment is a politically acceptable way of helping distressed urban areas.


Integrated care through disease-oriented clinical care pathways: experience from Japan's regional health planning initiatives.
In April 2008, Japan launched a radical reform in regional health planning that emphasized the development of disease-oriented clinical care pathways. These 'inter-provider critical paths' have sought to ensure effective integration of various providers ranging among primary care practitioners, acute care hospitals, rehabilitation hospitals, long-term care facilities and home care. All 47 prefectures in Japan developed their Regional Health Plans pursuant to the guideline requiring that these should include at least four diseases: diabetes, acute myocardial infarction, cerebrovascular accident and cancer. To illustrate the care pathways developed, this paper describes the guideline referring to strokes and provides examples of the new Regional Health Plans as well as examples of disease-oriented inter-provider clinical paths. In particular, the paper examines the development of information sharing through electronic health records (EHR) to enhance effective integration among providers is discussed. Japan's reform in 2008 is unique in that the concept of 'disease-oriented regional inter-provider critical paths' was adopted as a national policy and all 47 prefectures developed their Regional Health Plans simultaneously. How much the new regional health planning policy has improved the quality and outcome of care remains to be seen and will be evaluated in 2013 after the five-year planned period of implementation has concluded. Whilst electronic health records appear to be a useful tool in supporting care integration they do not guarantee success in the application of an inter-provider critical path.


Understanding thoracic outlet syndrome.
The diagnosis of thoracic outlet syndrome was once debated in the world of vascular surgery. Today, it is more understood and surprisingly less infrequent than once thought. Thoracic outlet syndrome (TOS) is composed of three types: neurogenic, venous, and arterial. Each type is in distinction to the others when considering patient presentation and diagnosis. Remarkable advances have been made in surgical approach, physical therapy, and rehabilitation of these patients. Dedicated centers of excellence with multidisciplinary teams have been developed and continue to lead the way in future research.


Prospective, Randomized, Open-Label, Blinded End Point, Two-Arm, Comparative Clinical Study to Evaluate the Efficacy and Safety of a Fixed Ayurvedic Regimen (FAR) as Add-on to Conventional Treatment in the Management of Mild and Moderate COVID-19 Patients.
The traditional healthcare systems are being avidly looked into in the quest for effective remedies to tackle the menace of COVID-19 pandemic. This was a prospective randomized, controlled open-label, blinded end point (PROBE) study to evaluate the efficacy and safety of a fixed ayurvedic regimen (FAR) as an add-on to conventional treatment/standard of care (SOC) in the management of mild-to-moderate COVID-19 infection. A total of 68 patients were recruited who consumed either FAR + SOC (n = 35) or SOC only (n = 33) for 28 days. Primary outcomes assessed were mean time required for clinical recovery and proportion of patients showing clinical recovery between the groups. Secondary outcomes assessed included mean time required for testing SARS-CoV-2 negative, change in clinical status on World Health Organization (WHO) ordinal scale, number of days of hospitalization, change in disease progression and requirement of oxygen/intensive care unit admission/ventilator support/rescue medication, health status on WHO quality of life (QOL) BREF and safety on the basis of occurrence of adverse event/serious adverse event (AE/SAE) and changes in laboratory parameters. Patients consuming FAR as an add-on SOC showed faster clinical recovery from the day of onset of symptoms by 51.34% (P < 0.05) as compared to SOC group. A higher proportion of patients taking FAR recovered within the first 2 weeks compared to those taking only SOC. It was observed that 5 times more patients recovered within 7 days in FAR group when compared to SOC (P < 0.05) group. An earlier clinical recovery was observed in clinical symptoms such as sore throat, cough, loss of taste and myalgia (P < 0.05). Improvement in postclinical symptoms such as appetite, digestion, stress and anxiety was also obs served to be better with the use of FAR. Requirement of rescue medications such as antipyretics, analgesics and antibiotics was also found to be reduced in the FAR group (P < 0.05). FAR showed a significant improvement in all the assessed domains of QOL. None of the AEs/SAE reported in the study were assessed to be related to the study drugs. Further, FAR did not produce any significant change in the laboratory safety parameters and was assessed to be safe. FAR could be an effective and safe add-on ayurvedic regimen to standard of care in the management of mild and moderate COVID-19 patients. CTRI number: CTRI/2020/09/027914.


Excited-State Dynamics and Nonlinear Optical Properties of Hyperpolarizable Chromophores Based on Conjugated Bis(terpyridyl)Ru(II) and Palladium and Platinum Porphyrinic Components: Impact of Heavy Metals upon Supermolecular Electro-Optic Properties.
A new series of strongly coupled oscillators based upon (porphinato)Pd, (porphinato)Pt, and bis(terpyridyl)ruthenium(II) building blocks is described. These RuPPd, RuPPt, RuPPdRu, and RuPPtRu chromophores feature bis(terpyridyl)Ru(II) moieties connected to the (porphinato)metal unit via an ethyne linker that bridges the 4'-terpyridyl and porphyrin macrocycle meso-carbon positions. Pump-probe transient optical data demonstrate sub-picosecond excited singlet-to-triplet-state relaxation. The relaxed lowest-energy triplet (T1) excited states of these chromophores feature absorption manifolds that span the 800-1200 nm spectral region, microsecond triplet-state lifetimes, and large absorptive extinction coefficients [ε(T1 → Tn) > 4 × 104 M-1 cm-1]. Dynamic hyperpolarizability (βλ) values were determined from hyper-Rayleigh light scattering (HRS) measurements carried out at several incident irradiation wavelengths over the 800-1500 nm spectral region. Relative to benchmark RuPZn and RuPZnRu chromophores which showed large βHRS values over the 1200-1600 nm range, RuPPd, RuPPt, RuPPdRu, and RuPPtRu displayed large βHRS values over the 850-1200 nm region. Generalized Thomas-Kuhn sum (TKS) rules and experimental hyperpolarizability values were utilized to determine excited state-to-excited state transition dipole terms from experimental electronic absorption data and thus assessed frequency-dependent βλ values, including two- and three-level contributions for both βzzz and βxzx tensor components to the RuPPd, RuPPt, RuPPdRu, and RuPPtRu hyperpolarizability spectra. These analyses qualitatively rationalize how the βzzz and βxzx tensor elements influence the observed irradiation wavelength-dependent hyperpolarizability magnitudes. The TKS analysis suggests that supermolecules related to RuPPd, RuPPt, RuPPdRu, and RuPPtRu will likely feature intricate dependences of experimentally determined βHRS values as a function of irradiation wavelength that derive from substantial singlet-triplet mixing, and complex interactions among multiple different β tensor components that modulate the long wavelength regime of the nonlinear optical response.


Specific disruption of Tsc1 in ovarian granulosa cells promotes ovulation and causes progressive accumulation of corpora lutea.
Tuberous sclerosis complex 1 (Tsc1) is a tumor suppressor negatively regulating mammalian target of rapamycin complex 1 (mTORC1). It is reported that mice lacking Tsc1 gene in oocytes show depletion of primordial follicles, resulting in premature ovarian failure and subsequent infertility. A recent study indicated that deletion of Tsc1 in somatic cells of the reproductive tract caused infertility of female mice. However, it is not known whether specific disruption of Tsc1 in granulosa cells influences the reproductive activity of female mice. To clarify this problem, we mated Tsc1(flox/flox) mice with transgenic mice strain expressing cyp19-cre which exclusively expresses in granulosa cells of the ovary. Our results demonstrated that Tsc1(flox/flox); cyp19-cre mutant mice were fertile, ovulating more oocytes and giving birth to more pups than control Tsc1(flox/flox) mice. Progressive accumulation of corpora lutea occurred in the Tsc1(flox/flox); cyp19-cre mutant mice with advanced age. These phenotypes could be explained by the elevated activity of mTORC1, as indicated by increased phosphorylation of rpS6, a substrate of S6 in the Tsc1(flox/flox); cyp19-cre mutant granulosa cells. In addition, rapamycin, a specific mTORC1 inhibitor, effectively rescued the phenotype caused by increased mTORC1 activity in the Tsc1(cko) ovaries. Our data suggest that conditional knockout of Tsc1 in granulosa cells promotes reproductive activity in mice.


A novel soft tissue model for biomaterial-associated infection and inflammation - bacteriological, morphological and molecular observations.
Infection constitutes a major risk for implant failure, but the reasons why biomaterial sites are more vulnerable than normal tissue are not fully elucidated. In this study, a soft tissue infection model was developed, allowing the analysis of cellular and molecular responses in each of the sub-compartments of the implant-tissue interface (on the implant surface, in the surrounding exudate and in the tissue). Smooth and nanostructured titanium disks with or without noble metal chemistry (silver, gold, palladium), and sham sites, were inoculated with Staphylococcus epidermidis and analysed with respect to number of viable bacteria, number, viability and gene expression of host cells, and using different morphological techniques after 4 h, 24 h and 72 h. Non-infected rats were controls. Results showed a transient inflammatory response at control sites, whereas bacterial administration resulted in higher recruitment of inflammatory cells (mainly polymorphonuclear), higher, continuous cell death and higher gene expression of tumour necrosis factor-alpha, interleukin-6, interleukin-8, Toll-like receptor 2 and elastase. At all time points, S. epidermidis was predominantly located in the interface zone, extra- and intracellularly, and lower levels were detected on the implants compared with surrounding exudate. This model allows detailed analysis of early events in inflammation and infection associated to biomaterials in vivo leading to insights into host defence mechanisms in biomaterial-associated infections.


Supine posture changes lung volumes and increases ventilation heterogeneity in cystic fibrosis.
Lung Clearance Index (LCI) is recognised as an early marker of cystic fibrosis (CF) lung disease. The effect of posture on LCI however is important when considering longitudinal measurements from infancy and when comparing LCI to imaging studies. 35 children with CF and 28 healthy controls (HC) were assessed. Multiple breath washout (MBW) was performed both sitting and supine in triplicate and analysed for LCI, Scond, Sacin, and lung volumes. These values were also corrected for the Fowler dead-space to create 'alveolar' indices. From sitting to supine there was a significant increase in LCI and a significant decrease in FRC for both CF and HC (p<0.01). LCI, when adjusted to estimate 'alveolar' LCI (LCIalv), increased the magnitude of change with posture for both LCIalv and FRCalv in both groups, with a greater effect of change in lung volume in HC compared with children with CF. The % change in LCIalv for all subjects correlated significantly with lung volume % changes, most notably tidal volume/functional residual capacity (Vtalv/FRCalv (r = 0.54,p<0.001)). There is a significant increase in LCI from sitting to supine, which we believe to be in part due to changes in lung volume and also increasing ventilation heterogeneity related to posture. This may have implications in longitudinal measurements from infancy to older childhood and for studies comparing supine imaging methods to LCI.


Multifaceted roles of PGE2 in inflammation and cancer.
Prostaglandin E(2) (PGE(2)) is a bioactive lipid that elicits a wide range of biological effects associated with inflammation and cancer. PGE(2) exerts diverse effects on cell proliferation, apoptosis, angiogenesis, inflammation, and immune surveillance. This review concentrates primarily on gastrointestinal cancers, where the actions of PGE(2) are most prominent, most likely due to the constant exposure to dietary and environmental insults and the intrinsic role of PGE(2) in tissue homeostasis. A discussion of recent efforts to elucidate the complex and interconnected pathways that link PGE(2) signaling with inflammation and cancer is provided, supported by the abundant literature showing a protective effect of NSAIDs and the therapeutic efficacy of targeting mPGES-1 or EP receptors for cancer prevention. However, suppressing PGE(2) formation as a means of providing chemoprotection against all cancers may not ultimately be tenable, undoubtedly the situation for patients with inflammatory bowel disease. Future studies to fully understand the complex role of PGE(2) in both inflammation and cancer will be required to develop novel strategies for cancer prevention that are both effective and safe.


Autologous immune complex nephritis in streptozotocin-induced diabetic rats.
In order to investigate the influence of diabetes mellitus on immune complex-mediated nephritis , we produced Heymann nephritis in streptozotocin-induced diabetic rats (DM-HN group) in which the clinical course for 24 weeks and histological changes were examined. Nondiabetic rats with Heymann nephritis (HN group) and diabetic rats (DM group) were also examined as controls. The degree of proteinuria, hypoproteinemia, hyperlipidemia and anemia were more pronounced and the mortality rate was higher in the DM-HN group than in the HN group or in the DM group. Histologically, larger and more subepithelial or intramembranous electron-dense deposits as well as a more markedly thickened glomerular basement membrane (GBM) were observed in the DM-HN group than in the HN group. In conclusion, the nephrotic manifestations and histological changes in the GBM in Heymann nephritis were augmented by the association with diabetes mellitus.


Multidetector helical CT of the liver for tumor detection and characterization.
Multidetector-row CT (MDCT) scanners have been recently introduced into clinical practice. Major attributes that are improved are the z-axis coverage speed and the longitudinal resolution. These improvements translate into rapid hepatic imaging and allow new imaging protocols. Thin sections can now be used on a routine basis in single-breath-hold technique. This results in improved lesion detection and the nearly isotropic image acquisition provides high-resolution multiplanar reformations. Furthermore, the ability to scan through the entire liver in 10 s or less allows acquisition of two separate sets of CT images of the liver within the time generally regarded as the hepatic arterial dominant phase in monoslice CT; thus, MDCT may demonstrate three clear separate distinct hepatic circulatory phases with a triple-pass technique. Multidetector-row CT with the improvements in morphological and functional information compared with single-slice CT enables a comprehensive approach to hepatic imaging within a single examination.


Cortical area MSTd combines visual cues to represent 3-D self-movement.
As arboreal primates move through the jungle, they are immersed in visual motion that they must distinguish from the movement of predators and prey. We recorded dorsal medial superior temporal (MSTd) cortical neuronal responses to visual motion stimuli simulating self-movement and object motion. MSTd neurons encode the heading of simulated self-movement in three-dimensional (3-D) space. 3-D heading responses can be evoked either by the large patterns of visual motion in optic flow or by the visual object motion seen when an observer passes an earth-fixed landmark. Responses to naturalistically combined optic flow and object motion depend on their relative directions: an object moving as part of the optic flow field has little effect on neuronal responses. In contrast, an object moving separately from the optic flow field has large effects, decreasing the amplitude of the population response and shifting the population's heading estimate to match the direction of object motion as the object moves toward central vision. These effects parallel those seen in human heading perception with minimal effects of objects moving with the optic flow and substantial effects of objects violating the optic flow. We conclude that MSTd can contribute to navigation by supporting 3-D heading estimation, potentially switching from optic flow to object cues when a moving object passes in front of the observer.


Sequence capture-PCR improves detection of mycobacterial DNA in clinical specimens.
The rapid identification of mycobacterial DNA in clinical samples by PCR can be useful in the diagnosis of tuberculous infections, but several large studies have found that the sensitivity of this approach is not better than that of culture. In order to improve the sensitivity of detection of mycobacterial DNA in clinical specimens from patients with paucibacillary forms of tuberculosis, we have developed a procedure permitting the specific capture of mycobacterial DNA in crude samples prior to amplification, thereby concentrating the target sequences and removing irrelevant DNA and other potential inhibitors of the amplification reaction (sequence capture-PCR). By using this approach to capture and amplify two different sequences specific for organisms of the Mycobacterium tuberculosis complex (IS6110 and the direct repeat region), it was possible to detect as little as one genome of mycobacterial DNA in samples containing up to 750 micrograms of total DNA, representing a 10- to 100-fold increase in sensitivity compared with that obtained by purifying total DNA prior to amplification. Detection of the IS6110 sequence in pleural fluid samples from patients with tuberculous pleurisy by sequence capture-PCR gave positive results in 13 of 17 cases, including 3 of 3 culture-positive samples and 10 of 14 culture-negative samples. In contrast, when total DNA was purified from these samples by adsorption to a silica matrix prior to amplification, only the three culture-positive samples were positive by PCR. The sensitivity of detection of the direct repeat sequence in these samples by sequence capture-PCR was similar to that of IS6110 and, in addition, permitted immediate typing of the strains from some patients. We conclude that sequence capture-PCR improves the sensitivity of detection of mycobacterial DNA in paucibacillary samples. This approach should be useful in detecting rare target sequences from organisms implicated in other pathologic processes.


The Effect of Heuristics on the Reasoning of the Pre-Service Science Teachers on the Topic of Melting and Boiling Point.
The purpose of this study was to explore the effects of the heuristics on the reasoning processes of pre-service science teachers on the topic of melting and boiling point using the ten heuristic model proposed by Talanquer. In this phenomenographic study carried out in the spring semester of the 2018-2019 academic year, interviews were conducted with 30 teacher candidates enrolled in the Science Teaching Program of Firat University Faculty of Education. Participants were asked to answer three different questions during the interviews. These questions were about the ranking of some compounds according to their melting or boiling points. Six different answer patterns for each question were obtained from the answers. The findings of this study showed that students generally used shortcut strategies instead of analytical/scientific reasoning, as all ten heuristics affected participants' reasoning. This study also revealed that although not included in the model proposed by Talanquer, periodic trends heuristic also influenced participants' reasoning about the melting and boiling point.


Gap of knowledge in diagnosis of pyoderma gangrenosum in clinical specialties education.
Pyoderma gangrenosum (PG) is a chronic ulcerative neutrophilic dermatosis. It presents a diagnostic challenge due to the absence of disease-specific markers or histopathology, lack of universally accepted diagnostic criteria, and many mimicking diseases including necrotizing soft tissue infections (NSTI). PG cases often present first to specialties other than dermatology. We reviewed major educational resources in internal medicine, family medicine, and infectious disease for their coverage of PG. For each specialty, we reviewed five major textbooks, five prominent journals, and any commonly used online resources. Twelve of 15 textbooks mentioned PG, only three of which included a differential, with none including NSTI in the differential. Only two of 13 journals included review articles about PG, and none of these including NSTI in their differential. Interestingly, online resources tended to be the most complete; six of nine contained PG articles, nearly all including a differential and three listing NSTI within it. We found an underrepresentation of PG among major textbooks and journals in clinical specialties, especially in differentiating PG from its mimickers. While online resources may help fill this gap in knowledge, texts and journals remain essential. Misdiagnosis and resultant mismanagement of PG can lead to disastrous outcomes. We recommend that PG be added to the differential diagnoses of chronic ulcers in educational resources. We also suggest the addition of identification and differentiation of PG to learning materials and lectures for providers in specialties who may encounter PG, NSTI, or similarly presenting diseases to address this gap.


Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6.
To explore the mechanisms involved in the pathogenesis of human multiple myeloma (MM), we investigated the potential role of interleukin-6 (IL-6), a B-cell differentiation factor in humans, and a growth factor for rat/mouse heterohybridomas and murine plasmacytomas. Using a heterohybridoma assay, we found that two well-documented human myeloma cell lines, RPMI 8226 and U266, did not secrete IL-6 and did not express RNA messengers for IL-6. Neutralizing antibodies to IL-6 did not inhibit their proliferation, and recombinant IL-6 did not stimulate it. Taken together, these data show that IL-6 is not the autocrine growth factor of these human myeloma cell lines. A high production of IL-6 was found in the bone marrows of patients with fulminating MM, compared with patients with inactive or slightly active MM, or to healthy donors. This IL-6 production was assigned to adherent cells of the bone-marrow environment but not to myeloma cells. A spontaneous proliferation of myeloma cells freshly isolated from patients was observed in short-term cultures. Recombinant IL-6 was able to amplify it two- to threefold. The spontaneous proliferation of the myeloma cells was inhibited by anti-IL-6 antibodies and reinduced by recombinant IL-6. After 2 to 3 weeks of culture, the myeloma-cell proliferation progressively declined and no IL-6-dependent myeloma cell lines could be obtained despite repeated additions of fresh IL-6 and costimulation with other cytokines such as tumor necrosis factor (TNF)beta, or IL-1 beta. These data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6.


Simultaneous determination of noradrenaline and dopamine in Portulaca oleracea L. by capillary zone electrophoresis.
A simple and rapid capillary electrophoretic method was developed for the simultaneous determination of noradrenaline (NA) and dopamine (DA) in Portulaca oleracea L. The buffer solution used in this method was 40 mM tris (hydroxymethyl) aminomethane (Tris)-H3PO4 at pH 2.00 containing 15% methanol. The effects of pH value, organic modifier, and applied voltage were investigated. The linear ranges of NA and DA were 0.5-100 microg/mL (r=0.9952) and 6.25-200 microg/mL (r=0.9992), respectively. The relative standard deviations of the corrected peak area were 6.73% and 4.26%, respectively. NA and DA in Portulaca oleracea L. were simultaneous determined successfully within 5.6 min. In this way, the contents of NA and DA in different parts (stem, leaves, and seeds) of P. oleracea L. and in different extracts of leaves with different solvents (distilled water, 50% methanol, and methanol) were studied.


The Association and Interaction of Aldehyde Dehydrogenase 2 Polymorphisms with Food Group Intake and Probability of Having Non-Alcoholic Fatty Liver Disease.
This study investigated the association between the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, food group intake, and the probability of having non-alcoholic fatty liver disease (NAFLD) in a Chinese population. A total of 3506 adults were enrolled in this study, and all underwent physical examinations and genotyping of polymorphisms with polymerase chain reaction. Participants filled out a dietary questionnaire that was used to assess the frequency and quantity of food consumption. We found that milk groups were associated with a lower probability of developing NAFLD. On the contrary, meat and salted and smoked foods were associated with a higher probability of NAFLD. However, the influences of salted and smoked foods and fresh fruit and vegetables on NAFLD were obviously different in the two genotype groups. Salted and smoked foods intake was a factor associated with a higher probability of having NAFLD or nonalcoholic steatohepatitis (NASH) in the A genotype group, but there was no effect in the G genotype group. Moreover, eating salted and smoked foods several times per week was associated with a higher probability of having NAFLD than seldom consuming them. Consumption of fresh fruit and vegetables was not a factor influencing the probability of having NAFLD in the A genotype group, and there was no effect in the G genotype group. Further analysis of the interaction indicated that the GA +AA genotype showed an interaction with fresh fruit and vegetables and salted and smoked foods. Moreover, it was not obvious that meat intake increased the probability of having NAFLD or NASH among different genotypes. Our results indicate that ALDH2 rs671 GA and AA genotypes are factors associated with increased probability of NAFLD among Chinese subjects. This could stimulate the development of novel approaches for preventing NAFLD.


The motif of falling: falling and the loss of the mother.
Falling carries the meaning of loss of the mother for three patients studied psychoanalytically. Falling carries the same implication in various tropes, myths and biblical imagery. This convergence of evidence supports the thesis that falling is a symbol of maternal loss.