Weight and weight control behaviors of Latinas and their social ties.
Shared behaviors have been implicated in the clustering of obesity among socially connected people. This study determined how weight and weight control behaviors of participants and their social ties are related and how these factors are associated with weight change in participants. Adult Latinas participating in a lifestyle intervention completed an egocentric network measure of weight and weight control behaviors. Participant weight was objectively measured at baseline and 12 months. Multivariable regression models determined the relationship between weight and weight control behaviors of participants and their social ties. Participants and their social ties shared similarities in weight control behaviors and weight change. Participants who reported social ties that had lost weight were more likely to eat small portions and low-fat foods, but those with social ties that had gained weight were more likely to use herbal supplements. Participants who reported more social ties who exercised, drank liquid meal replacements, took herbal supplements, and self-weighed were more likely to lose weight whereas those with fewer social ties that exercised were more likely to gain weight. Weight loss and weight gain by social ties predicted participant weight loss and weight gain, respectively. Given that weight and weight control behaviors of Latinas reflect that of their social ties, targeting existing social networks for lifestyle interventions may more effectively improve and sustain health-promoting behaviors and outcomes. (PsycINFO Database Record


Development of Hydrotaea aenescens (Diptera: Muscidae) in manure of unweaned dairy calves and lactating cows.
In laboratory studies performed in the United States and Hungary, the dump fly Hydrotaea aenescens (Wiedemann) was reared successfully in manure of 1- to 8-wk-old dairy calves, and in manure from adult lactating dairy cows. Survival in manure collected from 1-wk-old calves was poor (7.2%), better in manure collected from 2- and 3-wk-old calves (53.5%), and best in manure collected from 4- to 8-wk-old calves (71.4%). Survival in cow manure was slightly lower (47.4%) than that in calf manure. Reasons for different rates of development in the United States and in Hungary, and by calf age are discussed as are implications for biological control.


Neuroprotective Mechanisms of Glucagon-Like Peptide-1-Based Therapies in Ischemic Stroke: An Update Based on Preclinical Research.
The public and social health burdens of ischemic stroke have been increasing worldwide. Hyperglycemia leads to a greater risk of stroke. This increased risk is commonly seen among patients with diabetes and is in connection with worsened clinical conditions and higher mortality in patients with acute ischemic stroke (AIS). Therapy for stroke focuses mainly on restoring cerebral blood flow (CBF) and ameliorating neurological impairment caused by stroke. Although choices of stroke treatment remain limited, much advance have been achieved in assisting patients in recovering from ischemic stroke, along with progress of recanalization therapy through pharmacological and mechanical thrombolysis. However, it is still necessary to develop neuroprotective therapies for AIS to protect the brain against injury before and during reperfusion, prolong the time window for intervention, and consequently improve neurological prognosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are broadly regarded as effective drugs in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data on GLP-1 and GLP-1 RAs have displayed an impressive neuroprotective efficacy in stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS), and other neurodegenerative diseases. Based on the preclinical studies in the past decade, we review recent progress in the biological roles of GLP-1 and GLP-1 RAs in ischemic stroke. Emphasis will be placed on their neuroprotective effects in experimental models of cerebral ischemia stroke at cellular and molecular levels.


For ED, the Doctor Is In But the Men Are Staying Away.
Men's health care changed dramatically after the FDA approved Pfizer's blue, diamond-shaped Viagra. Suddenly men were interested in seeing their doctors if for only one reason. Now, with restrictions on what some call a lifestyle drug, other health problems go uncharted.


Oxidative stress and mitochondrial dysfunction in Kindler syndrome.
Kindler Syndrome (KS) is an autosomal recessive skin disorder characterized by skin blistering, photosensitivity, premature aging, and propensity to skin cancer. In spite of the knowledge underlying cause of this disease involving mutations of FERMT1 (fermitin family member 1), and efforts to characterize genotype-phenotype correlations, the clinical variability of this genodermatosis is still poorly understood. In addition, several pathognomonic features of KS, not related to skin fragility such as aging, inflammation and cancer predisposition have been strongly associated with oxidative stress. Alterations of the cellular redox status have not been previously studied in KS. Here we explored the role of oxidative stress in the pathogenesis of this rare cutaneous disease. Patient-derived keratinocytes and their respective controls were cultured and classified according to their different mutations by PCR and western blot, the oxidative stress biomarkers were analyzed by spectrophotometry and qPCR and additionally redox biosensors experiments were also performed. The mitochondrial structure and functionality were analyzed by confocal microscopy and electron microscopy. Patient-derived keratinocytes showed altered levels of several oxidative stress biomarkers including MDA (malondialdehyde), GSSG/GSH ratio (oxidized and reduced glutathione) and GCL (gamma-glutamyl cysteine ligase) subunits. Electron microscopy analysis of both, KS skin biopsies and keratinocytes showed marked morphological mitochondrial abnormalities. Consistently, confocal microscopy studies of mitochondrial fluorescent probes confirmed the mitochondrial derangement. Imbalance of oxidative stress biomarkers together with abnormalities in the mitochondrial network and function are consistent with a pro-oxidant state. This is the first study to describe mitochondrial dysfunction and oxidative stress involvement in KS.


Imaging of peripheral PNET: common and uncommon locations.
We present the imaging features of peripheral primitive neuroectodermal tumour (PNET) in eight children, highlighting the unusual locations of this tumour in three children. At presentation, the tumours were studied with magnetic resonance imaging (MRI; n = 6), computed tomography (CT; n = 7) and ultrasound (US; n = 1). The diagnoses were confirmed histologically (n = 8), immunohistochemically (n = 8), by cytogenetics (n = 3) and electron microscopy (n = 1). Correlation with gross pathology, histology, treatment and outcome were obtained. The tumours were located in the chest wall (n = 2), shoulder, pelvis, small bowel mesentery, adrenal gland, dura mater and skin and subcutaneous tissue of the abdominal wall (n = 1 each). Peripheral PNET arising from the small bowel mesentery, adrenal gland and dura mater have not been previously reported in the English literature. The tumours were mainly large (mean size: 10.6 cm) and infiltrative. All tumours were heterogeneously hyperintense on T2-weighted MRI, heterogeneously iso/hypodense on CT and had variable contrast enhancement. Most tumours were heterogeneously hypointense to muscle on T1-weighted MRI. US showed a hypoechoic mass with a cystic component. Peripheral PNET can occur in unusual locations. The clinical and imaging features of peripheral PNET are non-specific, making tissue diagnosis essential. PNET should be included in the differential diagnosis of aggressive soft tissue tumours in children.


How to prevent postoperative ileus in colorectal surgery? a systematic review.
Postoperative ileus (PI) after colorectal surgery is a common surgical problem. This systematic review aimed to investigate the available data in the literature to reduce the PI in the area of colorectal surgery out of the enhanced recovery after surgery principles, referring to published randomized controlled trials (RCTs) and meta-analyses, and to provide recommendations according to the Oxford Centre for Evidence-Based Medicine. The authors conducted bibliographic research on 1 December 2022. The authors retained meta-analyses and RCTs. The authors concluded that when we combined colonic mechanical preparation with oral antibiotic decontamination, the authors found a significant reduction in PI. The open approach was associated with a higher PI rate. The robotic and laparoscopic approaches had similar PI rates. Low ligation of the inferior mesenteric artery presented a PI similar to that of high ligation of the inferior mesenteric artery. There was no difference between the isoperistaltic and antiperistaltic anastomoses or between the intracorporeal and extracorporeal anastomoses. This study summarized the available data in the literature, including meta-analyses and RCTs. For a higher level of evidence, additional multicenter RCTs and meta-analyses of RCTs remain necessary.


Salient alternatives facilitate implicatures.
Sentences can be enriched by considering what the speaker does not say but could have done, the alternative. We conducted two experiments to test whether the salience of the alternative contributes to how people derive implicatures. Participants responded true or false to underinformative categorical sentences that involved quantifiers. Target sentences were sometimes preceded by the alternative and sometimes by a control sentence. When the target was preceded by the alternative, response times to implicature responses were faster than when preceded by the control sentence. This suggests that (1) alternative salience influences higher-level reasoning (2) the cost of deriving implicatures in sentence verification paradigms is due in part to low alternative salience.


Is there a role for a specialist physiotherapist in the multi-disciplinary management of women with stress incontinence referred from primary care to a specialist continence clinic?
Our objective was to assess the benefit of additional pelvic floor exercises, supervised by specialist physiotherapists, in the secondary care management of urinary stress incontinence. This is a retrospective cohort study in a UK University teaching hospital. A total of 317 women were referred from primary care to a specialist continence clinic for management of urinary stress incontinence. The cases were identified from the clinic database and a case note review performed. Data were collected on initial clinical assessment, suitability for pelvic floor exercises and outcome of treatment. The main outcome measures were adherence to primary care guidelines, suitability for further pelvic floor exercises and outcome of exercises. In total, 201 women were deemed suitable for a trial of further pelvic floor exercises, of whom 82 had previously attempted this in the primary care setting. After completing a course of physiotherapist supervised exercises, 105 women were able to be discharged from secondary care as a result of their symptoms improving. Of these women, 46 had previously attempted pelvic floor exercises in the community. It was seen that the primary care guidelines are poorly adhered to and where pelvic floor exercises are attempted in the community, the outcomes appear to be suboptimal. In appropriately selected women, a trial of additional physiotherapist-supervised exercises is beneficial and can reduce the urodynamic and surgical workload by 33%.


Novel insights into the disease dynamics of B-cell lymphomas in the Genomics Era.
High-throughput sequencing has significantly contributed to revealing the molecular underpinnings of B-cell lymphomagenesis and disease progression. It is now a widely accepted concept that the diversity of clinical responses to front-line therapy and the development of relapsed/refractory disease are in part explained by 'inter-patient' genetic heterogeneity measurable by individual sets of somatic gene alterations in tumor genomes. Moreover, extensive 'intra-tumor' heterogeneity on the genotypic and phenotypic levels is the product of ongoing tumor evolution and adaptation to various selective pressures during cancer initiation, progression, and therapeutic intervention. As the management of disease progression remains one of the most significant clinical challenges, it is becoming increasingly important to delineate how B-cell lymphomas evolve over time and to develop progression-related biomarker assays. Toward this goal, recent investigations have moved from studying lymphoma biology at initial diagnosis to doing so at multiple time points during the disease course. Profiling progressed tumors, and in particular paired biopsies at initial diagnosis and disease progression of the same patients, has led to novel insights into clonal tumor evolution and tumor microenvironment dynamics. This review discusses the latest findings on genomic alterations and microenvironment biology associated with relapsed/refractory B-cell lymphomas, with a particular emphasis on alterations that are acquired or become more prevalent at disease progression. We also describe overarching tumor evolution patterns, and highlight emerging precision medicine methodologies that can aid in an improved understanding and management of relapsed/refractory disease. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Prophylaxis of breast cancer among women over 35.
In recent years, the increase in incidence of malignant tumours of breast has been observed in Poland. Every year approximately 10 thousands of new cases of breast cancer are registered. 19 per cent of all women afflicted with malignant neoplasms suffer from breast cancer. According to considerable experience of the western countries, prophylaxis combined with screening examinations is the most effective and, also, the cheapest method of fighting against neoplasm. In the face of steadily growing danger, which affects more and more women, an attempt to assess the knowledge and behaviour towards prophylaxis of breast cancer among women over 35 was made. The researches, carried out between April and November 2002, were conducted with the use of our own questionnaire basing upon literature on the subject. The poll was intended for women aged between 35 and 60. The group of 300 women, who live in the south-east part of Poland, was surveyed. A detailed analysis of the data revealed that almost 50 per cent of women know the rules of preventive actions in the spheres of breast self-control and mammography. The level of knowledge of primary prophylaxis correlates with the level of education of women. The higher is education, the greater is knowledge about the risk factors of breast cancer. The highly educated women more often and more systematic take preventive actions leading to early detection of breast cancer. The women in the 35-45 age group more regularly and more often perform monthly breast self-control. Also the fact of the prevalence of breast cancer in the members of the polled women's families raises the discipline of performed examination.


Methyltransferase-directed DNA strand scission.
We demonstrate here that MTase-modified DNA can undergo the Staudinger ligation with triarylphosphines derivatized with phenanthroline. Presentation of these duplexes with Cu(II) and 3-mercaptopropionic acid leads to strand scission proximal to the MTase recognition site. By virtue of their ability to use a synthetic azide-bearing cofactor, M.TaqI and M.HhaI produce a DNA lesion that induces scission 5' to the base modified by the enzyme. This chemistry represents a new approach by which regions of DNA methylation can be rapidly identified on the basis of DNA damage.


Practice management - tips from the toolkit: 3 governance.
More than most small businesses, medical practices require good governance. One of the qualities most expected of a family doctor is trust. This encompasses not just doing the right thing by patients but also our colleagues, employees, business partners and the community. In this article, we reflect on some of the aspects of governance as it applies in general practice. This series is based on The Royal Australian College of General Practitioners' 'General practice management toolkit'.


[Clinicopathologic significance of chromosomal DNA sequence copy number aberrations in patients with colorectal carcinoma].
To analyze the correlation of DNA sequence copy number aberrations (DSCNAs)with clinicopathologic parameters in patients with colorectal cancer(CRC). Comparative genomic hybridization (CGH) method was used in analysis of 73 cases with CRC. Statistical analysis was performed using Stat View statistical software package(5.0). Loss of 8pl2-pter and gain of 8q23-qter were linked to nodal metastasis, while loss of 18q12-qter and gain of 8q23-qter were associated with distant organ metastasis at diagnosis and (or) recurrence after surgery. Moreover, losses of 8pl2-pter and 18q12-qter and gain of 8q23-qter were associated significantly with unfavorable prognosis. Multivariate analysis revealed that loss of 18q12-qter was an independent prognostic marker. Our findings indicate that genetic aberrations detected by CGH may predict outcome in patients with CRC, and may provide useful information for clinical treatment. Comparative genomic hybridization;


MUSIC® for Medical Students: Confirming the Reliability and Validity of a Multi-Factorial Measure of Academic Motivation for Medical Education.
Construct: The MUSIC® Inventory measures the construct of academic motivation across five factors: empowerment, usefulness, success, interest, and caring. The factors are defined in terms of the degree the student perceives that they have control over their environment, that the coursework is useful to their future, that they can succeed in the course, that the course and instructional methods are interesting, and that the teacher cares about their wellbeing and their success respectively. Background: A valid measure of medical students' academic motivation would provide medical teachers with a method for evaluating the motivational aspect of their course and provide focus for changes in teaching and learning to improve medical student engagement. While the MUSIC® Inventory structure has been validated in the tertiary setting and with several professional programs, it has not been validated with medical students. The aim of this study was to use both classical test theory and Rasch modeling to assess the reliability and confirm the structure of the five-factor model of the MUSIC® Inventory with medical students. Approach: One-hundred-fifty-two medical students completed the 26-item inventory. Descriptive statistics, internal consistency, correlations between factors, confirmatory factor analysis, and Rasch analysis using the rating scale model were performed to determine reliability and validity. Findings: The five factors showed good internal consistency (Cronbach's alpha .87 - .92). Correlations between factors were moderate to high (r = .38 - .89). Confirmatory factor analysis highlighted inconsistencies in factor loadings of three of the items hypothesized to measure interest. Rasch analysis using the rating scale model showed that all items for each factor had good item fit (0.65 - 1.37). Person separation (2.28 - 2.85) and reliability (.84 -.91) scores indicated that the scales were able to differentiate different levels of respondents. Item separation (2.25 - 6.97) and reliability scores (.83 -.98) indicated that the items of the scales were being differentiated by the respondents. Conclusions: Rasch analysis indicates that the five factors of academic motivation measured by the MUSIC® Inventory account for the response patterns in data from medical students. However, while the factors of empowerment, usefulness, success, and caring showed expected reliability and validity using classical analysis, three of the interest items cross-loaded on to the usefulness factor. Possible reasons may include ambiguity of language for the items or medical students' conception of usefulness and interest. Future research will explore medical students' understanding of the language used to measure these factors in further detail.


Occult hepatitis B infection among individuals belonging to the aboriginal Nicobarese tribe of India.
The long-lasting persistence of hepatitis B virus (HBV) genomes in the liver (with or without detectable HBV DNA) of individuals with negative for HBV surface antigen (HBsAg) is termed occult HBV infection (OBI). The present study is a part of the follow up on efficacy of vaccination, 10 years post inception, and was designed to understand the prevalence of Occult Hepatitis B infection (OBI) among the aboriginal Nicobarese tribal community. A total of 612 serum samples were collected and tested for various markers including HBsAg, Anti-HBs, Anti-HBc and HBV DNA. Part of S gene of the extracted HBV DNA was amplified by nested PCR. The amplified products were then subjected to sequencing. Genotyping was performed on the basis of phylogenetic relationship along with representative reference sequences from different sub genotypes. The study revealed OBI in 11.1% of the people belonging to the Nicobarese tribe. Phylogenetic analysis showed only one genotype, HBV/D circulating among the Nicobarese population with ayw3 was the major serotype detected. Single or multiple amino acids substitutions were found in 5 of 34 samples (14.7%) which includes I110T, P120T, P/T127I, A128P, M133L and G159V. The detection of OBI among these aboriginal tribes is of great concern and stresses the need for the continuous surveillance as it may contribute to the progression of liver disease to a more advanced stage.


Does endogenous or exogenous adenosine facilitate the functional recovery of the cochlea after ischemia?
The present study was undertaken to determine whether adenosine attenuates cochlear dysfunction induced by transient ischemia. Adenosine or erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor, was administered by perilymphatic perfusion to albino guinea pigs that were subjected to cochlear ischemic episodes of 30-minute duration. The threshold shift of the compound action potential (CAP) from the preischemic value was significantly reduced in the animals perfused with EHNA 1 hour after the onset of reperfusion. However, perfusion of adenosine at concentrations of 100 micromol/L to 10 mmol/L did not reduce the postischemic CAP threshold shift by either 1 hour or 4 hours after the onset of reperfusion. These results suggest that the elevation of the adenosine concentration did not exert a protective effect on the cochlear ischemia-reperfusion injury, and that the protective action of EHNA is unrelated to elevating the adenosine concentration.


Serotonin regulates macrophage-mediated angiogenesis in a mouse model of colon cancer allografts.
Serotonin, a neurotransmitter with numerous functions in the central nervous system (CNS), is emerging as an important signaling molecule in biological processes outside of the CNS. Recent advances have implicated serotonin as a regulator of inflammation, proliferation, regeneration, and repair. The role of serotonin in tumor biology in vivo has not been elucidated. Using a genetic model of serotonin deficiency (Tph1(-/-)) in mice, we show serotonin to be crucial for the growth of s.c. colon cancer allografts in vivo. Serotonin does not enhance tumor cell proliferation but acts as a regulator of angiogenesis by reducing the expression of matrix metalloproteinase 12 (MMP-12) in tumor-infiltrating macrophages, entailing lower levels of angiostatin-an endogenous inhibitor of angiogenesis. Accordingly, serotonin deficiency causes slower growth of s.c. tumors by reducing vascularity, thus increasing hypoxia and spontaneous necrosis. The biological relevance of these effects is underscored by the reconstitution of serotonin synthesis in Tph1(-/-) mice, which restores allograft phenotype in all aspects. In conclusion, we show how serotonin regulates angiogenesis in s.c. colon cancer allografts by influencing MMP-12 expression in tumor-infiltrating macrophages, thereby affecting the production of circulating angiostatin.


Lanthanide-containing light-emitting organic-inorganic hybrids: a bet on the future.
Interest in lanthanide-containing organic-inorganic hybrids has grown considerably during the last decade, with the concomitant fabrication of materials with tunable attributes offering modulated properties. The potential of these materials relies on exploiting the synergy between the intrinsic characteristics of sol-gel derived hosts (highly controlled purity, versatile shaping and patterning, excellent optical quality, easy control of the refractive index, photosensitivity, encapsulation of large amounts of isolated emitting centers protected by the host) and the luminescence features of trivalent lanthanide ions (high luminescence quantum yield, narrow bandwidth, long-lived emission, large Stokes shifts, ligand-dependent luminescence sensitization). Promising applications may be envisaged, such as light-emitting devices, active waveguides in the visible and near-IR spectral regions, active coatings, and bio-medical actuators and sensors, opening up exciting directions in materials science and related technologies with significant implications in the integration, miniaturization, and multifunctionalization of devices. This review provides an overview of the latest advances in Ln(3+)-containing siloxane-based hybrids, with emphasis on the different possible synthetic strategies, photoluminescence features, empirical determination.


Biomedical materials to meet the challenges of the aging epidemic.
The number and percentage of people throughout the world who will be 60 years of age and older are steadily growing due to reduced fertility rate and longer life expectancy. We are facing the prospect that large numbers of individuals in countries throughout the world will be living longer with disability and pain resulting from age-related disorders. We have a wide array of biomedical materials that could serve as the basis for treatments to deal with these problems. It is important to begin now to investigate how these biomaterials can be deployed in conjunction with the necessary biologics to treat lesions at an early stage of their development, while meeting the criteria of low cost and minimal invasiveness.


Morphological study of the Paneth cell. Paneth cells in intestinal metaplasia of the stomach and duodenum of man.
The Peneth cells in intestinal metaplasia of stomach and the duodenum in human subjects were studied ultrastructurally, and the fine structures of these cells were compared. Paneth cells showed the ultrastructure of serozymogenic cells and secreted their secretory granules by merocrine process. The rod or tubular dense bodies were observed in the apical region of some Paneth cells. The structures may have some relation to the secretion of the secretory granules. The secretory granules with less dense layer in the periphery, which had never been described in the Paneth cell of man, were also observed. Morphologically intermediate cells between Paneth cell and goblet cell were found. Some of the Paneth cells might be phagocytized by undifferentiated crypt cells. The Paneth cells in intestinal metaplasia were fundamentally the same as those in duodenum at least in morphology. Difference between them was that Paneth cells with many phagolysosomes in the lower cytoplasm were observed more frequently in the duodenum than in intestinal metaplasia of the stomach. The physiological functions of the Paneth cell have been discussed.


Lipidaemic effects of tocotrienols, tocopherols and squalene: studies in the hamster.
Syrian Golden hamsters have been widely used as a experimental model for the investigation of the aetiology and development of atherosclerosis and cardiovascular disease. The responses of the hamster to dietary fat manipulations are in many ways similar to that observed in humans. The lipidaemic effect of a tocotrienol rich fraction (TRF) from palm oil on human trials has not been consistent. In this study, the cholesterolaemic effect of tocotrienols and tocopherols were differentiated by using pure tocotrienols (that were isolated from palm oil fatty acid distillate) and pure commercial tocopherols and squalene. A palm oil triacylglycerol fraction (POTG), free of all unsaponifiable matter, was used as the dietary fat in different feeding experiments. Tocotrienols added at 162 ppm to POTG (POTG-T3L) significantly (p<0.05) lowered serum total cholesterol (TC) level as compared to that of the POTG group; but the serum LDL-C , HDL-C and TG levels of the POTG-T3L group were not significantly lower than that of the POTG group (P>0.05). Increasing the level of tocotrienol supplementation to the diet (POTG-T3H) appeared to raise rather then reduce the serum TC, LDL-C and HDL-C levels as compared to that of POTG-T3L group. This observation that lower level of tocotrienol supplementation appeared to exhibit stronger hypocholesterolaemic effect than a higher level of tocotrienol supplementation is interesting; but its explanation is not yet forthcoming. When tocopherols were supplemented at 72 ppm to the POTG diet it was observed that the serum TC, LDL-C and HDL-C levels were all somewhat increased when compared to that of the POTG group. These results suggest that tocotrienols and tocopherols may have opposite cholesterolaemic effects in the hamster, and further experiments need to clarify the mode of action of these vitamin E isomers. In our second series of experiments the cholesterolaemic effects of tocotrienols and tocopherols were studied in the presence of squalene, a key intermediate in the cholesterol synthesis pathway and a controversial cholesterol lowering agent. Squalene added to the diet at 0.1% level significantly lowered (p<0.05) serum TC level when compared to that of the POTG group. The LDL-C, HDL-C and TG levels appeared to be lowered by the squalene supplementation also but the differences between the POTG-SQ and POTG groups were not statistically significant (P>0.05). When tocotrienols or tocopherols were added to the squalene-containing POTG diets, the serum TC and LDL-C levels were further reduced (p<0.01) when compared to that of the POTG and POTG-SQ groups. The HDL-C and TG levels were not affected by tocotrienol or tocopherol supplementation in the presence of squalene. These results indicate that in the presence of tocotrienols and squalene POTG exhibit hypocholesterolaemic action whereas tocopherols may have a hypercholesterolaemic effect in the hamster.


Monofixation with eso-, exo-, or hypertropia: is there a difference?
Monofixation syndrome is considered the next best thing to bifoveal fixation because it allows excellent binocular vision and long-term stability of alignment in patients with small angle strabismus. The purpose of this study was to determine if there exists an anatomic or physiologic reason for the visual system to prefer small angle esotropia over exotropia or hypertropia. Of 259 cases of strabismus ≤10(Δ), esotropia was the most common and the most stable form of microtropia. Stability was statistically associated with sensory fusion, motor fusion, and stereopsis. Micro-ET cases outperformed the exotropic and hypertropic cases in all sensory categories, but particularly in the case of motor fusion. Instability was associated with the presence of an A- or V-pattern, oblique dysfunction, a history of infantile esotropia, dense amblyopia, and a significant change in refractive error. Micro-XT and HT were more likely to display these signs. In order to ensure long-term stability through fusion and stereopsis, the visual cortex must link the fovea of the dominant eye with the nasal retina in esotropic eyes, or the temporal retina in exotropic eyes. However, temporal retinal input is at a competitive anatomic and physiologic disadvantage. Compared to the connections necessary for binocular vision in micro-ET, those required for XT or HT may be more difficult to form and easily disrupted once established.


Angiogenesis induced by B-cell non-Hodgkin's lymphomas. Lack of correlation with tumor malignancy and immunologic phenotype.
Correlations of malignancy grade, immunologic phenotype and angiogenic capacity were studied in B-cell non-Hodgkin's lymphomas grafted onto chorioallantoic membranes of chicken embryos. The angiogenic response elicited by the tumors was significantly greater than the response to normal lymph nodes, but it did not correlate with either the malignancy grade or the immunologic phenotype of the tumors. The elevated angiogenic capacity of neoplastic tissues is confirmed. The results also suggest that the extensive vasoproliferative response required by a rapidly growing tumor is not only controlled by the neoplastic cell population but, probably, by the host-response as well.


High prevalence of dementia among people with learning disabilities not attributable to Down's syndrome.
For many years, it has been known that dementia can occur in people with learning disabilities, but there have been few research studies. Studies that do quote rates for dementia show these to be high, but this important fact has received remarkably little attention. Comprehensive psychiatric and medical assessments were undertaken on the whole population (ascertained as far as is possible) of people with learning disabilities aged 65 years and over living in Leicestershire, UK (N = 134), in order to ascertain rates of DCR defined dementia, and associated factors. Dementia was diagnosed in 21.6%, against an expected prevalence of 5.7%, for a group with this age structure. The rate of dementia increased in successive age cohorts: 15.6% aged 65-74 years; 23.5% aged 65-84 years; and 70.0% aged 85-94 years. People with dementia tended to be older, female, with more poorly controlled epilepsy, a larger number of additional physical disorders, less likely to be smokers and had lower adaptive behaviour scores than did the elderly people without dementia. They were more likely to live in health service accommodation. Dementia occurs at a much higher rate among elderly people with learning disabilities than it does among the general population; this is independent of the association between dementia and Down's syndrome. Whether this relates aetiologically to genetics, lack of brain 'reserve' or history of brain damage is yet to be determined.


Cardiovascular response to dopamine and early prediction of outcome in septic shock: a prospective multiple-center study.
To compare mortality rates between dopamine-sensitive (Dopa-S) and dopamine-resistant (Dopa-R) septic shock patients, the latter group defined by a mean arterial pressure <70 mm Hg despite the use of 20 mug/kg/min dopamine. A human, prospective observational, multiple-center, clinical trial. Ten intensive care units from ten hospitals. 110 patients with septic shocks. Following volume resuscitation, patients were treated by a rapid increase in dopamine infusion from 10 to 20 mug/kg/min. If mean arterial pressure remained <70 mm Hg, dopamine treatment was promptly switched to norepinephrine or epinephrine. Dopamine sensitivity, arterial gas, lactate, and organ system failure scores were measured at admission and after 6, 12, 24, 48, 72, 96, and 120 hrs. The overall 28-day mortality rate was 54% for the entire population under study. In multivariate analysis, independent predictors of death were dopamine resistance (odds ratio, 9.5; 95% confidence interval, 3-25), arterial lactate >3.5 mmol/L (odds ratio, 1.75; 95% confidence interval, 1.06-2.55), and Sepsis-related Organ Failure Assessment score >10 (odds ratio, 1.40; 95% confidence interval, 1.07-2.12). Of the 110 patients studied, 66 were observed to be resistant to dopamine (60%). In the Dopa-S group, the 28-day mortality rate was 16% (seven of 44 patients) compared with 78% (52 of 66 patients) in the Dopa-R group (p = .0006). The capacity of dopamine resistance to predict death was associated with a sensitivity of 84% and a specificity of 74%. At 24 hrs, the association of dopamine resistance to a lactate level >3.5 mmol/L improved the prognostic value (sensitivity, 90%, specificity, 92%). Dopamine sensitivity is associated with decreased mortality rate. Early recognition of dopamine resistant septic shock could allow for better screening of patients with an ominous prognosis.


Chromothripsis 18 in multiple myeloma patient with rapid extramedullary relapse.
Catastrophic chromosomal event known as chromothripsis was proven to be a significant hallmark of poor prognosis in several cancer diseases. While this phenomenon is very rare in among multiple myeloma (MM) patients, its presence in karyotype is associated with very poor prognosis. In our case, we report a 62 year female patient with rapid progression of multiple myeloma (MM) into extramedullary disease and short overall survival (OS = 23 months). I-FISH investigation revealed presence of gain 1q21 and hyperdiploidy (+ 5,+ 9,+ 15) in 82% and 86%, respectively, while IgH rearrangements, del(17)(p13) and del(13)(q14) were evaluated as negative.Whole-genome profiling using array-CGH showed complex genomic changes including hyperdiploidy (+ 3,+ 5,+ 9,+ 11, + 15,+ 19), monosomy X, structural gains (1q21-1q23.1, 1q32-1q44, 16p13.13-16p11.2) and losses (1q23.1-1q32.1; 8p23.3-8p11.21) of genetic material and chromothripsis in chromosome 18 with 6 breakpoint areas. Next-generation sequencing showed a total of 338 variants with 1.8% (6/338) of pathological mutations in NRAS (c.181C > A; p.Gln61Lys) or variants of unknown significance in TP53, CUX1 and POU4F1. Our findings suggest that presence of chromothripsis should be considered as another important genetic hallmark of poor prognosis in MM patients and utilization of genome-wide screening techniques such as array-CGH and NGS improves the clinical diagnostics of the disease.


PGE2 exerts its effect on the LPS-induced release of TNF-alpha, ET-1, IL-1alpha, IL-6 and IL-10 via the EP2 and EP4 receptor in rat liver macrophages.
Lipopolysaccharide (LPS) induces a release of tumor necrosis factor (TNF)-alpha, endothelin (ET)-1, interleukin (IL)-1alpha, IL-6 and IL-10 in rat liver macrophages (Kupffer cells). Prostaglandin (PG)E2 inhibits the release of the fibrogenic mediators TNF-alpha, ET-1 and IL-1alpha, and enhances the release of the anti-fibrogenic mediators IL-6 and IL-10. This effect of PGE2 is mimicked by specific agonists for the PGE2 receptors EP2 and EP4; whereas, agonists for the PGE2 receptors EP1 and EP3 are inactive. Rat liver macrophages express mRNA encoding the PGE2 receptors EP2 and EP4 but not the PGE2 receptors EP1 and EP3. These data suggest that PGE2 exerts its anti-fibrogenic effect through the EP2 and EP4 receptor by inhibiting the release of the fibrogenic mediators TNF-alpha, ET-1 and IL-1alpha, and by enhancing the release of the anti-fibrogenic mediators IL-6 and IL-10 in liver macrophages.


Insertion torque/time integral as a measure of primary implant stability.
The goal of this in vitro study was to determine the insertion torque/time integral for three implant systems. Bone level implants (n = 10; BLT - Straumann Bone Level Tapered 4.1 mm × 12 mm, V3 - MIS V3 3.9 mm × 11.5 mm, ASTRA - Dentsply-Sirona ASTRA TX 4.0 mm × 13 mm) were placed in polyurethane foam material consisting of a trabecular and a cortical layer applying protocols for medium quality bone. Besides measuring maximum insertion torque and primary implant stability using resonance frequency analysis (RFA), torque time curves recorded during insertion were used for calculating insertion torque/time integrals. Statistical analysis was based on ANOVA, Tukey's honest differences test and Pearson product moment correlation (α = 0.05). Significantly greater mean maximum insertion torque (59.9 ± 4.94 Ncm) and mean maximum insertion torque/time integral (961.64 ± 54.07 Ncm∗s) were recorded for BLT implants (p < 0.01). V3 showed significantly higher mean maximum insertion torque as compared to ASTRA (p < 0.01), but significantly lower insertion torque/time integral (p < 0.01). Primary implant stability did not differ significantly among groups. Only a single weak (r = 0.61) but significant correlation could be established between maximum insertion torque and insertion torque/time integral (p < 0.01) when all data from all three implant groups were pooled. Implant design (length, thread pitch) seems to affect insertion torque/time integral more than maximum insertion torque.


Xerostomia, Hyposalivation, and Salivary Flow in Diabetes Patients.
The presence of xerostomia and hyposalivation is frequent among diabetes mellitus (DM) patients. It is not clear if the presence of xerostomia and hyposalivation is greater in DM than non-DM patients. The aims of this systematic review are (1) to compare the prevalence rates of xerostomia, (2) to evaluate the salivary flow rate, and (3) to compare the prevalence rates of hyposalivation in DM versus non-DM population. This systematic review was conducted according to the PRISMA group guidelines by performing systematic literature searches in biomedical databases from 1970 until January 18th, 2016. All studies showed higher prevalence of xerostomia in DM patients in relation to non-DM population, 12.5%-53.5% versus 0-30%. Studies that analyzed the quantity of saliva in DM population in relation to non-DM patients reported higher flow rates in non-DM than in DM patients. The variation flow rate among different studies in each group (DM/CG) is very large. Only one existing study showed higher hyposalivation prevalence in DM than non-DM patients (45% versus 2.5%). In addition, quality assessment showed the low quality of the existing studies. We recommend new studies that use more precise and current definitions concerning the determination and diagnosis of DM patients and salivary flow collection.


Standoff Detection System Using Raman Spectroscopy in the Deep-Ultraviolet Wavelength Region for the Detection of Hazardous Gas.
This study developed a standoff detection system for Raman spectra in the deep-ultraviolet region to facilitate remote detection of various hazardous materials. Although Raman spectroscopy can distinguish various materials, the measurement of Raman spectra through standoff detection is challenging because of the low scattering cross-section of Raman scattering. The resonance Raman scattering effect in the deep-ultraviolet wavelength region is promising in terms of enhancing the spectral intensity of Raman scattering. A catoptric light receiver system was developed to effectively collect deep-ultraviolet light via a change in the distance from the primary to secondary mirror of the telescope. The experimental results for the standoff detection indicate that the system enables the measurement of the Raman spectrum of SO2 gas, which was locally present 20 m from the system with a wavelength resolution of 0.15 nm. The gas used in this remote measurement has a relatively simple molecular structure among chemical, biological, radiological, nuclear, and explosive gases. However, the high wavelength resolution of Raman spectroscopy will enable measurement of substances with complex molecular structures, such as bacteria and explosives, without losing the detailed structure of their spectra.


Large-area metal-dielectric heterostructures for surface-enhanced raman scattering.
Metal-dielectric heterostructures have shown great application potentials in physics, chemistry and material science. In this work, we have designed and manufactured ordered metal-dielectric multiple heterostructures with tunable optical properties, which can be as large as the order of square centimeters in size. We experimentally realized that the surface-enhanced Raman scattering signal of the periodic multiple heterostructures increased 50 times compared with the silicon nanodisk-gold film arrays, which is attributed to the large-scale hotspots and high efficient coupling between the optical cavities and surface plasmon resonance modes. More importantly, the substrate also features a good uniformity and an excellent reproducible fabrication, which is very promising for practical applications.


Surface-enhanced Raman spectroscopy + support vector machine: a new noninvasive method for prostate cancer screening?
Prostate cancer is one of the most common malignancies of the older males worldwide. Early diagnosis and treatment are important to improve the survival of patients. Recently, we developed a new method for prostate cancer screening: by measuring the serum surface-enhanced Raman spectroscopy of prostate cancer patients and normal subjects, combining with classification algorithms of support vector machines, the measured surface-enhanced Raman spectroscopy spectra are successfully classified with accuracy of 98.1%. Although the practical application faces several difficulties, we believe that this label-free serum surface-enhanced Raman spectroscopy analysis technique combined with support vector machine diagnostic algorithms will become a powerful tool for noninvasive prostate cancer screening in the future.


Modernization and the status of the frail elderly: Perspectives on continuity and change.
Regardless of whether important changes in the status and roles of the young-old have occurred as societies modernize, attitudes and behavior toward frail, dependent elders have been remarkably consistent over time and place: though sometimes tolerated, they have never been valued. This paper reviews the evidence for their continuing low status over time, using four overlapping perspectives: the frail elderly as resource, as impediment, as low priority, and as victim. The conclusion is that over the course of human history there has been more continuity than change for the frail elderly as assets, as burden, and as low priority. But processes associated with modernization, especially in the medical sphere, have exacerbated their plight as potential victims; death-hastening and delayed death are the two major types of victimization discussed. Finally, implications for aging societies worldwide are considered.


Gastric Lipoma: A Review of the Literature.
Gastric lipoma is a rare benign tumor of the stomach. The imaging characteristics are diagnostic because the lesion has fat attenuation on computed tomography and demonstrates characteristics of fat on magnetic resonance images. On ultrasound, the lesion can be identified as a lesion hypoechoic to the gastric mucosa that is soft, but the mass cannot be displaced with compression. Identifying these imaging characteristics can prevent biopsy or surgery in asymptomatic patients. Although this lesion is benign, it can cause gastric obstruction.


Infusion tomography of the gallbladder.
Infusion tomography of the gallbladder has proved to be more specific in the detection of pathologic disease as compared with conventional roentgenologic examinations by showing the wall of the organ instead of the contents. Infusion tomography of the gallbladder has been a useful initial procedure in patients with acute cholecystitis and in those with obstructive jaundice. It has helped to confirm diagnosis in patients with chronic lithiasic cholecystitis and nonvisualized gallbladder or with gallstones with documented on oral or intravenous studies. Infusion tomography of the gallbladder can be done on an emergency basis; it requires no prior preparation of the patient and usually yields an answer within 30 minutes. No significant complications have resulted from the high dose of iodized contrast material. There have been only two false results, one negative and one positive, so the procedure can be regarded as a highly reliable one.


The impact of saponins or saponin-containing plant materials on ruminant production--a review.
Saponins are steroid or triterpene glycoside compounds found in a variety of plants. Some saponin-containing plants, mainly legumes, have been used as animal feed, but others are toxic. Several studies on the effect of saponins on ruminant production have also been reported. Some in vitro and in vivo experiments that demonstrate the beneficial effects of saponin such as defaunation of the rumen and manipulation of the end products of fermentation are described. Defaunation is the selective removal of protozoa from the rumen microbial ecosystem by a cell membrane cholesterol-saponin interaction, which causes cell rupture. Because protozoa in the rumen cause protein turnover by predating on bacteria, defaunation increases the nitrogen utilization of the ruminant and may lead to an increase in growth, milk, or wool production. The growth-promoting effect was evident in the high roughage diet suggesting that the application of saponins or saponin-containing plant materials may be beneficial for the subsistence farmers in developing countries. Saponins are deglycosylated by rumen microbes. Some sapogenins have been detected in the digestive tract of ruminants; however, the direct action of these compounds on the host animal is still unclear. No information on the effects of saponin on ruminant reproduction is available. There is an urgent need for a systematic evaluation of the most active structural components of the saponins, and their interaction with the microbial community, the host animal, and the diet. Along with these studies, the direct effects of saponins or their microbial degradation products on the host must be examined in order to get the full understanding of the metabolism and beneficial effects of saponins on animals.


A colourimetric high-throughput screening system for directed evolution of prodigiosin ligase PigC.
A colourimetric high-throughput screening system was established for directed evolution of prodigiosin ligase PigC. The two-step system consists of a colony prescreening test and a subsequent photometric 96-well plate assay. Screening PigC epPCR libraries in Pseudomonas putida revealed a PigC variant that achieved a 2.9× increased yield of prodiginine derivatives.


Anthropological research perspectives on health problems in developing countries.
Anthropological research on health problems in developing countries during the past 30 years, and present/future research on the same topic, are considered in the light of (a) the changing health picture in developing countries and (b) the major health enterprises of developing countries and participating multilateral and bilateral agencies. The author suggests that modern medicine in recent years has become the first choice of most traditional peoples most of the time. It is because the supply of modern health care cannot keep up with the demand that the Primary Health Care (PHC) movement has arisen. With respect to the use of traditional curers in PHC it is pointed out that (a) they are not replacing themselves, (b) many have become ' neotraditional curers ' making extensive use of modern drugs and (c) spiritualist curing is replacing much traditional medicine. The question is, then, when we advocate the use of 'traditional curers ' in PHC programs, what exactly are we proposing? All of the above? Some of the above? Traditional healers only, strictly defined? The author also suggests that some early anthropological stereotypes of health behavior need revision, particularly those having to do with effective doctor-patient interaction. Finally, if anthropologists are effectively to explore the sociocultural aspects of health and illness, they must study health care delivery systems as intensively as community/patient behavior.


Alveolar soft part sarcoma: a single-center 26-patient case series and review of the literature.
Background. Alveolar soft part sarcoma (ASPS) is a rare tumor, and little information is available regarding its clinical features and appropriate treatments. Methods. A retrospective review of 26 consecutive ASPS patients (12 male, 14 female; mean age of 27 years) treated at our institution over 30 years (mean followup; 71 months) was performed. Results. The primary tumor developed in the lower extremity (12), trunk (8), and upper extremity (6), with an average size of 7.2 cm (range, 2-14 cm). The AJCC stage at presentation was IIA (7), III (3), and IV (16). Surgical excision was performed in 20 patients (R0 18, R1 plus radiotherapy 2) without local recurrence. Six patients (stage IIA 3/7, stage III 3/3) later developed metastases after an average period of 28.7 months. The median survival of the 26 patients was 90 months, with overall 5/10-year survival rates of 64%/48%. AJCC stage and tumor size were significant prognostic factors. Significant palliation and slowing of metastasis progression were achieved with gamma knife radiotherapy. Nine patients receiving chemotherapy showed no objective response. Conclusions. ASPS is indolent but has a high propensity for metastasis. Early diagnosis and complete excision of the small primary tumor are essential in the treatment of ASPS.


Effects of Age and Environment on Adaptive Immune Responses to Mycobacterium avium subsp. paratuberculosis (MAP) Vaccination in Dairy Goats in Relation to Paratuberculosis Control Strategies.
Paratuberculosis infection is caused by Mycobacterium avium subsp. paratuberculosis (MAP). In the Netherlands, 75% herd level prevalence of caprine paratuberculosis has been estimated, and vaccination is the principal control strategy applied. Most goat dairy farms with endemic paratuberculosis systematically vaccinate goat kids in the first months of life with a commercially available whole cell MAP vaccine. We hypothesized that the development of adaptive immune responses in goats vaccinated at young age depends on the environment they are raised in, and this has implications for the application of immune diagnostic tests in vaccinated dairy goats. We evaluated the early immune response to vaccination in young goat kids sourced from a MAP unsuspected non-vaccinated herd and raised in a MAP-free environment. Subsequently we compared these with responses observed in birth year and vaccination matched adult goats raised on farms with endemic paratuberculosis. Results indicated that initial adaptive immune responses to vaccination are limited in a MAP-free environment. In addition, adult antibody positive vaccinated goats raised in a MAP endemic environment are less likely to be IS900 PCR-positive as compared to antibody negative herd mates. We conclude that test-and-cull strategies in a vaccinated herd are currently not feasible using available immune diagnostic tests.


Multiple mycobacterial antigens in diagnostic tuberculins.
Guinea-pig antisera containing IgG1 antibodies have been prepared either with killed mycobacterial in paraffin oil or living BCG or intradermal injections of fractions of unheated culture filtrate. Sera, found to contain antibodies specific for different mycobacterial antigens are used in passive cutaneous anaphylaxis (PCA) in 12 times the dilution-to-extinction titer. Animals prepared with sera respond in all sites when unheated culture filtrate, strain H37Rv, is injected intravenously (i.v.) at 17-20 hours. Injection of diagnostic tuberculins i.v. into parallel recipients, in selected amounts, reveals, through reacting sites, the presence of the corresponding antigens and some information on relative amounts. Tuberculins of PPD type are precipitated from heated culture filtrate by ammonium sulfate or trichloroacetic acid (TCA) or benzoic acid. Old Tuberculins are made classically by long heating and evaporation. In all products heat-labile antigens are absent or present in small amount; yet, PPD-S was found to possess five antigens. In all PPD products, there was one dominant antigen, absent from Old Tuberculins. The dominant antigen of OT's was excluded from the TCA-PPD's but was present in most ammonium sulfate-type PPD's. It can be concluded that diagnostic testing made with OT detects a particular delayed-type sensitivity that is different in specificity from that which reacts to TCA-PPD's. Many but not all of the ammonium sulfate PPD's test for both specificities. Several different delayed-type sensitivities are acquired during infection. Supported by Grant AI 01258 of the National Institute of Health.


Genetic diversity of Shiga toxin-producing Escherichia coli O157 : H7 recovered from human and food sources.
The aim of this study was to identify an epidemiological association between Shiga toxin-producing Escherichia coli O157 : H7 strains associated with human infection and with food sources. Frequency distributions of different genetic markers of E. coli O157 : H7 strains recovered from human and food sources were compared using molecular assays to identify E. coli O157 : H7 genotypes associated with variation in pathogenic potential and host specificity. Genotypic characterization included: lineage-specific polymorphism assay (LSPA-6), clade typing, tir (A255T) polymorphism, Shiga toxin-encoding bacteriophage insertion site analysis and variant analysis of Shiga toxin 2 gene (stx2a and stx2c) and antiterminator Q genes (Q933 and Q21). The intermediate lineage (LI/II) dominated among both food and human strains. Compared to other clades, clades 7 and 8 were more frequent among food and human strains, respectively. The tir (255T) polymorphism occurred more frequently among human strains than food strains. Q21 and Q933 + Q21 were found at significantly higher frequencies among food and human strains, respectively. Moreover, stx2a and stx2a+c were detected at significantly higher frequencies among human strains compared to food strains. Bivariate analysis revealed significant concordance (P<0.05) between the LSPA-6 assay and the other typing methods. Multivariable regression analysis suggested that tir (255T) was the most distinctive genotype that can be used to detect bacterial clones with potential risk for human illness from food sources. This study supported previous reports of the existence of diversity in genetic markers among different isolation sources by including E. coli O157 : H7 strains from both food and human sources. This might enable tracking genotypes with potential risk for human illness from food sources.


Ultrasonic monitoring of bone fracture healing.
Quantitative ultrasound has attracted significant interest in the evaluation of bone fracture healing. Animal and clinical studies have demonstrated that the propagation velocity across fractured bones can be used as an indicator of healing. Researchers have recently employed computational methods for modeling wave propagation in bones, aiming to gain insight into the underlying mechanisms of wave propagation and to further enhance the monitoring capabilities of ultrasound. In this paper, we review the relevant literature and present the current status of knowledge.


Spatial and annual variability in concentrations and sources of Escherichia coli in multiple watersheds.
Nonpoint source fecal contamination is a concern for drinking water supplies worldwide. In this study, 4812 E. coli isolates were classified to source. Results of this experiment show that the fecal coliform (FC) counts varied by year, month, and site, for each of the watersheds sampled. For both years, the lowest FC counts tended to be at the highest elevation sites followed by the drinking water intake sites at the lowest elevation. The highest FC counts tended to be at the mid-elevation sites on BX, Deer, and Duteau Creeks. The sources of E. coli varied significantly with stream for 2003 and 2004 (P < 0.001, df = 39), although the main sources of E. coli (avian, deer/elk, canine, rodent, bovine, and bear) tended to be similar between watersheds. The dominant sources of E. coli changed from 2003 (avian, deer/elk, and canine) to 2004 (avian, bovine, and rodent). It is important to look at the results of more than 1 year of source tracking data to get a better picture of the dominant sources within a watershed. Overall, wildlife was the largest contributor of E. coli to the watersheds in both 2003 (> 84%) and 2004 (> 73%).


Rapid remote conditioning mediates modulation of blood cell paracrine activity and leads to the production of a secretome with neuroprotective features.
The indirect use of the protective potential of stem cells in the form of cell secretomes has become an attractive strategy in regenerative medicine. In the present work, we studied the paracrine activity of blood cells that could be modulated towards a neuroprotective nature using in vivo remote conditioning (i.e. tolerant blood cells). The increased neuronal survival mediated by the tolerant secretome was clearly confirmed in vitro in a model of glutamate toxicity in a primary culture of rat cortical neurons and in vivo in a pre- and post-treatment of rats that were subjected to transient occlusion of the middle cerebral artery. Bioinformatic-based analysis of the protein profile revealed higher amounts of proteins released by the tolerant blood cells; 29 proteins were recognised as secreted. More than half of these secreted proteins were involved in the biological processes of the response to the stimulus (GO:0050896) and the response to chemicals (GO:0042221). The protective phenotype was most likely mediated by the synergistic effect of multiple identified proteins, including unique to the tolerant secretome (ceruloplasmin, D-3-phosphoglycerate dehydrogenase) and was promoted by the co-participation of several reaction pathways. The most probably of these pathways were post-translation protein modification, MAP2K and MAPK activation and platelet activation. Taken together, our results demonstrate that properly stimulated blood cells could serve as a source for cell-free-based therapies of regenerative medicine.


Dermatological Considerations in the Diagnosis and Treatment of Marginal Zone Lymphomas.
Primary cutaneous marginal zone lymphoma (PC-MZL) is a B-cell lymphoma arising in the skin. Although it is a rare disease, PC-MZL accounts for 20-40% of all primary cutaneous B-cell lymphoma in Western Countries. The aetiology and the pathogenesis of PC-MZL are poorly understood, as it generally lacks the chromosomal translocations most typically present in marginal zone lymphomas of other sites. The diagnosis of PC-MZL may be challenging, due to the rarity of the disease, and needs the competence of different professional figures, including the dermatologist and the pathologist. Furthermore, the management of the patient after the diagnosis is complex and involves the dermatologist, the haematologist, the surgeon, the radiotherapist and the radiologist. The aim of this review is to describe the clinical and histological findings for the diagnosis of PC-MZL, and the state of art for the management of the patient.


Identification of crucial genes associated with rat traumatic spinal cord injury.
The aim of the present study was to investigate the key genes associated with traumatic spinal cord injuries (TSCI). The dataset GSE52763 was downloaded from the Gene Expression Omnibus, for which lumbar spinal cord samples were obtained from rats at 1 and 3 weeks following contusive spinal cord injury and 1 week subsequent to a sham laminectomy, and used to identify differentially expressed genes (DEGs). Functional enrichment analysis, co‑expression analysis and transcription factor (TF) identification were performed for DEGs common to the 1 and 3 week injury samples. In total, 234 upregulated and 51 downregulated DEGs were common to the 1 and 3 week injury samples. The upregulated DEGs were significantly enriched in Gene Ontology terms concerning immunity (e.g. Itgal and Ccl2) and certain pathways, including natural killer cell mediated cytotoxicity [e.g. Ras‑related C3 botulinum toxin substrate 2 (Rac2) and TYRO protein tyrosine kinase binding protein (Tyrobp)]. The downregulated DEGs were highly enriched in female gonad development [e.g. progesterone receptor (Pgr)], and the steroid biosynthesis pathway. A total of 139 genes had co‑expression associations and the majority of them were upregulated genes. The upregulated co‑expressed genes were predominantly enriched in biological regulation, including TGFB induced factor homeobox 1 (Tgif1) and Rac2. The downregulated co‑expressed genes were enriched in anatomical structure development (e.g. Dnm3). A total of 92 co‑expressed genes composed the protein‑protein interaction network. Additionally, 9 TFs (e.g. Pgr and Tgif1) were identified from the DEGs. It was hypothesized that the genes including Tgif1, Rac2, Tyrobp, and Pgr may be closely associated with TSCI.


Hyperbolic Gradient Operator and Hyperbolic Back-Propagation Learning Algorithms.
In this paper, we first extend the Wirtinger derivative which is defined for complex functions to hyperbolic functions, and derive the hyperbolic gradient operator yielding the steepest descent direction by using it. Next, we derive the hyperbolic backpropagation learning algorithms for some multilayered hyperbolic neural networks (NNs) using the hyperbolic gradient operator. It is shown that the use of the Wirtinger derivative reduces the effort necessary for the derivation of the learning algorithms by half, simplifies the representation of the learning algorithms, and makes their computer programs easier to code. In addition, we discuss the differences between the derived Hyperbolic-BP rules and the complex-valued backpropagation learning rule (Complex-BP). Finally, we make some experiments with the derived learning algorithms. As a result, we find that the convergence rates of the Hyperbolic-BP learning algorithms are high even if the fully activation functions are used, and discover that the Hyperbolic-BP learning algorithm for the hyperbolic NN with the split-type hyperbolic activation function has an ability to learn hyperbolic rotation as its inherent property.


Identification of sheep eimerian parasites, Eimeria crandallis and Eimeria faurei, employing microscopic and molecular tools.
Coccidiosis, caused by apicomplexan Eimeria species, is a protozoan disease that affects various species of wild and domestic animals. However, data available on Eimeria diversity in ruminants in Saudi Arabia is meagre. Therefore, this study was designed to investigate some eimerian parasites infecting sheep (Sawakni and Harrie breeds) using microscopy and molecular methods for the first time in Saudi Arabia. Twenty-four fecal samples were collected from sheep farms. Based on the floatation technique, eimerian oocysts were observed in 8 of the 24 (33.33%) fecal samples. The coccidian-positive samples were subjected to fecal culture in a shallow layer of 2.5% potassium dichromate (K2 Cr2 O7 ). Detected eimerian oocysts were described micromorphometrically as the basis for traditional oocyst identification. Morphologically, the sporulated oocysts were similar to those of sheep eimerian parasies; Eimeria faurei and Eimeria crandallis. PCR products from the two eimerian species detected from Sawakni and Harrie breeds were sequenced and were found to be distinct from each other with mutations at five positions. One of them clustered with E. crandallis with 99.8%-100% identity with sequences available in GenBank. E. crandallis was obtained from two Sawakni sheep and two Harrie sheep. The other sequences grouped with E. faurei with 99.8% identity with the only sequences available in GenBank. E. crandallis was detected from both Sawakni and Harrie breeds whereas E. faurei was detected only from Sawakni sheep. The findings of this study have implications for the importance of morphometric identification with advanced molecular tools to confirm the identities of sheep Eimeria species and to address the taxonomic study of this eimeriid parasite at the species level.


Intrinsic flexibility of NLRP pyrin domains is a key factor in their conformational dynamics, fold stability, and dimerization.
Nucleotide-binding domain leucine-rich repeat-containing receptors (NLRs) are key proteins in the innate immune system. The 14 members of the NLRP family of NLRs contain an N-terminal pyrin domain which is central for complex formation and signal transduction. Recently, X-ray structures of NLRP14 revealed an unexpected rearrangement of the α5/6 stem-helix of the pyrin domain allowing a novel symmetric dimerization mode. We characterize the conformational transitions underlying NLRP oligomerization using molecular dynamics simulations. We describe conformational stability of native NLRP14 and mutants in their monomeric and dimeric states and compare them to NLRP4, a representative of a native pyrin domain fold. Thereby, we characterize the interplay of conformational dynamics, fold stability, and dimerization in NLRP pyrin domains. We show that intrinsic flexibility of NLRP pyrin domains is a key factor influencing their behavior in physiological conditions. Additionally, we provide further evidence for the crucial importance of a charge relay system within NLRPs that critically influences their conformational ensemble in solution.


Variability in cecal intubation rate by calculation method: a call for standardization of key performance indicators in endoscopy.
The cecal intubation rate (CIR) is a widely accepted key performance indicator (KPI) in colonoscopy but lacks a universal calculation method. We aimed to assess whether differences in CIR calculation methods could have an impact on perceived trainee outcomes. A systematic review of CIR calculation methods was conducted on major societal guidelines (United Kingdom, European Society of Gastrointestinal Endoscopy [ESGE] and American Society for Gastrointestinal Endoscopy [ASGE]) and trainee-inclusive studies. Trainees awarded colonoscopy certification between June 2011 and 2016 were identified from the United Kingdom e-portfolio and selected as a validation cohort. For each trainee, both the crude and unassisted CIR were calculated for 50 post-certification procedures using definitions from the 3 international guidelines. The resulting CIRs, and the proportions of endoscopists failing to meet the minimum standard of CIR ≥90%, were then compared across these definitions. Across the 3 guidelines and 37 eligible studies identified, differences in CIR calculation methodology were demonstrated. These related to adjustment criteria (18 studies) and whether unassisted CIR was stipulated (18 studies). In the validation cohort of 733 trainees (36,650 procedures), the median crude CIR ranged from 96% (ESGE) to 98% (ASGE) (P < .001) and whether unassisted CIR was specified (ESGE, 94%; ASGE, 96%; P < .001). The proportion of trainees failing to achieve CIR ≥90% varied significantly across the different definitions, from 4.9% for the crude ASGE definition to 18.6% for the unassisted ESGE definition (P < .001). CIR calculation methods vary among guidelines and research studies; this has an impact on trainee performance measures. With CIR used as an example, this study highlights the need for standardized definitions and calculations of KPIs in endoscopy.


Axial motor disturbances after hypoxic lesions of the globus pallidus.
Four subjects aged between 29 and 60 years were examined because of axial motor impairment after hypoxic brain injury. Magnetic resonance imaging revealed circumscribed lesions of the globus pallidus in every case. The association of freezing of the gait, speech disorders, axial bradykinesia, and postural disturbances, with no rigidity or tremor and little or no distal akinesia, suggests a role of the globus pallidus in controlling axial motion.


Evaluating the biosafety of conventional and O3-BAC process and its relationship with NOM characteristics.
It is the priority to guarantee biosafety for drinking water treatment. The objective of this study was to evaluate the impact of widely applied conventional and ozone-biological activated carbon (O3-BAC) advanced treatment technology on biosafety of drinking water. The items, including assimilable organic carbon (AOC), biodegradable dissolved organic carbon (BDOC), heterotrophic plate counts (HPCs) and the microorganism community structures, were used to evaluate the biosafety. Moreover, their relationships with molecular weights (MWs) and fluorescence intensity of dissolved organic matter were investigated. The results indicated that the technology provided a considerable gain in potable water quality by decreasing dissolved organic carbon (DOC, from 5.05 to 1.71 mg/L), AOC (from 298 to 131 μg/L), BDOC (from 1.39 to 0.24 mg/L) and HPCs (from 275 to 10 CFU/mL). Ozone brought an increase in DOC with low MW <1 kDa, which accompanies with an increase in AOC/BDOC concentration, which could be reduced effectively by subsequent BAC process. The formation of AOC/BDOC was closely related to DOC with low MWs and aromatic protein. Bacteria could be released from BAC filter, resulting in an increase in HPC and the presence of pathogenic bacteria in effluent, while the post sand filter could further guarantee the biosafety of finished water.


Sertraline - isolation methods and quantitation in biological material.
Sertraline (SRT) is a modern and relatively safe selective serotonin reuptake inhibitor often used in the treatment of depression. Monitoring the body levels of this drug and its active metabolite, N-desmethylsertraline (DSRT), permits optimizing the dosage and personalizing the treatment, especially in the case of severe adverse reactions or lack of response to the applied therapy. The determination of SRT and DSRT in diagnostic material, i.e., blood, plasma, urine and saliva, and also in biological material from deceased persons, requires a variety of sensitive and reliable analytical methods to determine both the total drug level (blood) as well as the level of the unbound form (saliva and urine). This paper presents a detailed literature review of the methods of SRT and DSRT isolation from biological material and analytical techniques used for their determination. These include extractive procedures such as solid phase extraction and microextraction as well as liquid-liquid extraction. We pay particular attention to the parameters taken into account during optimization of extraction, i.e., the effect of pH, type of solvent and composition of the solvents mixture, on washing various types of sorbents (hydrophobic, hydrophilic-lipophilic and ion exchange) and elution of analytes. We show the advantages and disadvantages of the extraction techniques in terms of efficiency and precision of extraction. We also discuss protein precipitation as one of the more recent methods of sample purification. In our presentation of the final determination techniques, i.e., HPLC, LC and GC, we focus on the type of detector (UV, nitric-phosphate, MS) as the basic factor determining the sensitivity, expressed as the limits of detection and quantification achieved by a given method.


Severe Hypothermia Causing Ventricular Arrhythmia in Organophosphorus Poisoning.
Organophosphorus poisoning cases are routinely treated across all Intensive Care Units adjoining the rural areas where agriculture is the main source of income. We present a unique case of severe hypothermia seen in a case of organophosphorus poisoning, which led to electrocardiogram disturbances and life-threatening arrhythmias.


A remarkable case report of an interrupted inferior vena cava with hemiazygos and transhepatic continuation.
Inferior vena cava (IVC) interruption with azygos/hemiazygos continuation is an extremely uncommon congenital vascular anomaly, which may present with multiple variants. As a result, it is challenging to find in the literature the same anatomical variant. We report a unique case of an interrupted IVC with hemiazygos and transhepatic continuation in an 83-year-old female patient. The case was evaluated by performing Computed Tomography (CT) as imaging modality, with a multiphase protocol, able to detect accurately this complex vascular anomaly. The purpose of this case report is not only to present this remarkable case but also to briefly show the types of interrupted IVC, starting from the anatomy and the embryology of the IVC and the azygos system, and to discuss the value of imaging in detecting the vascular anomaly.


Immunoassay of serum alphafetoprotein and albumin reflects the mode of tissue preparation: implications for steroid hormone receptor assays.
The effect of various modes of tissue preparation on the retention of distinct serum proteins was determined. Specific and sensitive radioimmunologic methods were used to measure serum alphafetoprotein (AFP) and albumin(SA) in 105,000 x g hypotonic soluble (cytoplasm) and hypertonic (400mM KCl) solubilized pellets (nuclear extracts) from homogenates of immature rat estrogen target tissues. The tissue level of both serum antigens was influenced by the preparative method: cervical dislocation followed by organ isolation and a single rinse yielded the highest levels of apparent tissue AFP and SA while decapitation followed by exsanguination, organ isolation and multiple rinses resulted in the lowest levels. For the uterus, exposure of the uterine lumen enhanced reduction of serum antigen detection. The recommended procedure minimizes the inclusion of serum proteins which can interfere in the subsequent in vitro measurement of specific receptors in hormone responsive tissues.


Demographic and Clinical Characteristics Associated With Familiarity, Interest, and Use of Integrative Therapies Among Patients With Breast Cancer.
Integrative therapies reduce side effects from cancer treatment, though remain underutilized. There is a paucity of data on factors associated with familiarity, interest, and use of these therapies among breast cancer patients. A survey on familiarity, interest, and use of acupuncture, massage, meditation, music therapy, and yoga was conducted in patients enrolled in the Chicago Multiethnic Epidemiologic Breast Cancer Cohort. Familiarity and interest were assessed using a five-point Likert scale, and modeled using proportional odds regression. Use was per self-report, modeled using logistic regression. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were calculated. Of 1300 study participants, 59.6% were familiar with massage, 47.2% acupuncture, 46.9% meditation, 46.5% yoga, and 34.5% music therapy; 63.3% were interested in massage, 50.2% yoga, 47.9% meditation, 44.2% acupuncture, and 41.4% music therapy. Only 41.3% had used massage, 25.8% acupuncture, 18.7% yoga, 18.5% meditation, and 7.4% music therapy. Older age and lower education level were associated with lower familiarity and interest. Black patients were more likely than White patients to be interested. Patients' interest increased significantly when certain symptoms were treated. In the adjusted models, patients ages 40 to 65 were less likely than those ages <40 to have used massage (aOR 0.55, 95% CI: 0.31-0.98), yoga (aOR 0.52, 95% CI: 0.27-0.99), or meditation (aOR 0.47, 95% CI: 0.25-0.90). Patients with high school education were less likely than those with a graduate degree to have used acupuncture (aOR 0.42, 95% CI: 0.24-0.72), massage (aOR 0.39, 95% CI: 0.25-0.62), or meditation (aOR 0.26, 95% CI: 0.12-0.58). Having received chemotherapy was associated with increased interest in yoga (aOR 1.36, 95% CI: 1.07-1.73), massage (aOR 1.27, 95% CI: 1.01-1.59), or meditation (aOR 1.26, 95% CI: 1.01-1.57). Receipt of hormone therapy was not associated with interest or use. In this racially diverse cohort of patients, familiarity and interest of integrative therapies were high, while use was low. Older age and lower education level were associated with lack of interest and use. Chemotherapy was associated with interest, but hormone therapy was not. Strategies to promote the benefits and use of integrative therapies among breast cancer patients are needed.


Use of tolterodine in children with neurogenic detrusor overactivity: relationship between dose and urodynamic response.
Three exploratory studies were conducted to investigate the pharmacokinetics (PK) and safety of tolterodine in children 1 month to 15 years old with neurogenic detrusor overactivity. We urodynamically evaluated the dose and concentration effects of tolterodine to establish safe and effective dosing regimens. Three open-label, dose escalating studies were conducted in children with stable neurological disease and detrusor overactivity. In studies 1 (patient aged 1 month to 4 years) and 2 (5 to 10 years) patients received 0.03, 0.06 and 0.12 mg/kg tolterodine solution day twice daily for 4 weeks each. In study 3 (patient age 11 to 15 years) patients received 2, 4 and 6 mg tolterodine extended-release capsules once daily for 4 weeks each. PK was assessed after 8 weeks, urodynamic assessments were conducted after each 4-week dosing period and 3-day micturition diaries were completed. Patients in studies 1 (19) and 2 (15) showed some dose related increases in volume to first detrusor contraction and cystometric bladder capacity. In study 3 (11 patients) there were no obvious dose-response relationships. PK results from studies 1 and 2 suggest that there was no apparent effect of age (< or =10 y) on these parameters. In study 3 time of maximum observed serum concentration and apparent terminal half-life were delayed, which is consistent with the extended-release formulation. Tolterodine was well tolerated, and there was no apparent relationship between tolterodine dose and adverse events in any study. These results support the safety of age and body weight adjusted dosing regimens for further clinical evaluation of tolterodine in children with neurogenic detrusor overactivity.


Extrapolative microRNA precursor based SSR mining from tea EST database in respect to agronomic traits.
Tea (Camellia sinensis, (L.) Kuntze) is considered as most popular drink across the world and it is widely consumed beverage for its several health-benefit characteristics. These positive traits primarily rely on its regulatory networks of different metabolic pathways. Development of microsatellite markers from the conserved genomic regions are being worthwhile for reviewing the genetic diversity of closely related species or self-pollinated species. Although several SSR markers have been reported, in tea, the trait-specific Simple Sequence Repeat (SSR) markers, leading to be useful in marker assisted breeding technique, are yet to be identified. Micro RNAs are short, non-coding RNA molecules, involved in post transcriptional mode of gene regulation and thus effects on related phenotype. Present study deals with identification of the microsatellite motifs within the reported and predicted miRNA precursors that are effectively followed by designing of primers from SSR flanking regions in order to PCR validation. In addition to the earlier reports, two new miRNAs are predicting here from tea expressed tag sequence database. Furthermore, 18 SSR motifs are found to be in 13 of all 33 predicted miRNAs. Trinucleotide motifs are most abundant among all followed by dinucleotides. Since, miRNA based SSR markers are evidenced to have significant role on genetic fingerprinting study, these outcomes would pave the way in developing novel markers for tagging tea specific agronomic traits as well as substantiating non-conventional breeding program.


Electronic health record-wide association study for atrial fibrillation in a British cohort.
Atrial fibrillation (AF) confers a major healthcare burden from hospitalisations and AF-related complications, such as stroke and heart failure. We performed an electronic health records-wide association study to identify the most frequent reasons for healthcare utilization, pre and post new-onset AF. Prospective cohort study with the linked electronic health records of 5.6 million patients in the United Kingdom Clinical Practice Research Datalink (1998-2016). A cohort study with AF patients and their age-and sex matched controls was implemented to compare the top 100 reasons of frequent hospitalisation and primary consultation. Of the 199,433 patients who developed AF, we found the most frequent healthcare interactions to be cardiac, cerebrovascular and peripheral-vascular conditions, both prior to AF diagnosis (41/100 conditions in secondary care, such as cerebral infarction and valve diseases; and 33/100 conditions in primary care), and subsequently (47/100 conditions hospital care and 48 conditions in primary care). There was a high representation of repeated visits for cancer and infection affecting multiple organ systems. We identified 10 novel conditions which have not yet been associated with AF: folic acid deficiency, pancytopenia, idiopathic thrombocytopenic purpura, seborrheic dermatitis, lymphoedema, angioedema, laryngopharyngeal reflux, rib fracture, haemorrhagic gastritis, inflammatory polyneuropathies. Our nationwide data provide knowledge and better understanding of the clinical needs of AF patients suggesting: (i) groups at higher risk of AF, where screening may be more cost-effective, and (ii) potential complications developing following new-onset AF that can be prevented through implementation of comprehensive integrated care management and more personalised, tailored treatment. NCT04786366.


NMR structure of the apoptosis- and inflammation-related NALP1 pyrin domain.
Signaling in apoptosis and inflammation is often mediated by proteins of the death domain superfamily in the Fas/FADD/Caspase-8 or the Apaf-1/Caspase-9 pathways. This superfamily currently comprises the death domain (DD), death effector domain (DED), caspase recruitment domain (CARD), and pyrin domain (PYD) subfamilies. The PYD subfamily is most abundant, but three-dimensional structures are only available for the subfamilies DD, DED, and CARD, which have an antiparallel arrangement of six alpha helices as common fold. This paper presents the NMR structure of PYD of NALP1, a protein that is involved in the innate immune response and is a component of the inflammasome. The structure of NALP1 PYD differs from all other known death domain superfamily structures in that the third alpha helix is replaced by a flexibly disordered loop. This unique feature appears to relate to the molecular basis of familial Mediterranean fever (FMF), a genetic disease caused by single-point mutations.


Label-Free Intracellular Multi-Specificity in Yeast Cells by Phase-Contrast Tomographic Flow Cytometry.
In-flow phase-contrast tomography provides a 3D refractive index of label-free cells in cytometry systems. Its major limitation, as with any quantitative phase imaging approach, is the lack of specificity compared to fluorescence microscopy, thus restraining its huge potentialities in single-cell analysis and diagnostics. Remarkable results in introducing specificity are obtained through artificial intelligence (AI), but only for adherent cells. However, accessing the 3D fluorescence ground truth and obtaining accurate voxel-level co-registration of image pairs for AI training is not viable for high-throughput cytometry. The recent statistical inference approach is a significant step forward for label-free specificity but remains limited to cells' nuclei. Here, a generalized computational strategy based on a self-consistent statistical inference to achieve intracellular multi-specificity is shown. Various subcellular compartments (i.e., nuclei, cytoplasmic vacuoles, the peri-vacuolar membrane area, cytoplasm, vacuole-nucleus contact site) can be identified and characterized quantitatively at different phases of the cells life cycle by using yeast cells as a biological model. Moreover, for the first time, virtual reality is introduced for handling the information content of multi-specificity in single cells. Full fruition is proofed for exploring and interacting with 3D quantitative biophysical parameters of the identified compartments on demand, thus opening the route to a metaverse for 3D microscopy.


An investigation on solid state reactions in heat treated Au/Pd thin films for electrodes applications.
The interface between metals and oxides is particularly interesting. It has been the main topic of many research projects to illustrate that their properties are highly dependent on the structure of the interface. Poor adhesion between gold films and oxides is well known. On the basis of solid solution between the materials, the main effect of a Pd thin film as the adhesion layer between substrate and Au was investigated. Pure palladium and gold films were grown by electron beam evaporation sequentially on the SrTiO3 (001) single crystal substrates. After different annealing time (from 0.06 to 1.8 ks) at 500 degrees C, the growth sequence of the compositions between Au and Pd evolved as a results of the solid solution were investigated by means of X-ray photoelectron spectroscopy (XPS), X-ray diffraction. Meanwhile the surface morphology and the surface topography were examined respectively by scanning electron microscopy (SEM) and atomic force microscopy (AFM) observation. The effect of an intermediate Pd adhesion layer and its influence on the interfacial properties and morphology of the Au layer is investigated.


Understanding clinical trials in childhood cancer.
Clinical trials in paediatric cancer continue to be a key factor in progress toward better treatment and prognosis. Paediatricians and family physicians may be asked by patients and families for their advice regarding participation in such trials. The significant advances in the success of treatment of paediatric cancer have come, in part, from the high participation rate of patients in such studies. The present article reviews the definitions and goals of phase 1, 2 and 3 trials. A known and trusted physician or paediatrician can be helpful in conjunction with the oncologist in guiding patients and their families and helping them understand the risks and benefits of participation in clinical trials.


[Humoral immune response in breeding sows after vaccination with a herd-specific Chlamydophila abortus vaccine].
A chlamydial vaccine efficacy trial with assessment of the clinical acceptability and serum antibody responses was performed in breeding sows. A BGM cell culture derived vaccine containing 10(8)/ml formalin-inactivated purified elementary bodies (Eb.) in sterile 0.15 M saline was prepared from Chlamydophila (Ch.) abortus strain OCHL03/99 which has been isolated in the herd from a sample of vaginal discharge. Vaccination was performed as a randomised trial with parallel treatment of a vaccinated group (25 sows) and non-vaccinated control group (20 sows). Sows received two 2.0-ml doses of vaccine intramuscularly at a three week interval. Control sows were dosed with sterile 0.15 M saline, accordingly. Serological response to vaccination was measured by ELISA with a total of 204 blood serum samples (114 from the vaccine group; 90 from the control group) using crude chlamydial LPS as the antigen. Compared to the control group, vaccinated sows showed a marked primary and secondary IgG serum antibody response following the two vaccinations. Antibody levels peaked between week 7 and 14 after priming vaccination, declined incrementally until week 27 but remained significantly higher than the corresponding sham-immune control levels and the prevaccination values of the vaccine group (p < 0.05). Western blot analysis of solubilized whole Eb. of Ch. abortus, Ch. pecorum, and Chlamydia (C.) suis with pre- and postvaccination sera confirmed that vaccination induced an antibody response preferentially against a range of 13 chlamydial antigens including the 40 kDa MOMP of Ch. abortus. Clinical side effects consisting of a transient mild local inflammatory reaction at the site of injection were observed in approx. 30% of vaccinated sows. These results provide the basis for further clinical evaluation of the Ch. abortus vaccine to protect sows from chlamydia-induced reproductive disorders.


Microtubules influence compaction in preimplantation mouse embryos.
The role of microtubules during compaction of the 8-cell-stage mouse embryo was investigated using the drugs Taxol (which leads to a non-controlled polymerization of tubulin) and Nocodazole (which causes depolymerization of microtubules). Taxol inhibits compaction in most non-compacted embryos and reverses it in already compacted embryos. These effects were observed on both cell flattening (as judged by phase-contrast microscopy) and on cell surface polarization (as judged by scanning electron microscopy and the surface binding of fluorescent concanavalin A). In contrast Nocodazole does not inhibit cell flattening, but rather accelerates its completion. Nocodazole influences the detailed organization of the surface pole and appears to reduce the incidence of surface polarization but does not reverse polarity once established to a significant extent. We conclude that microtubules exercise a constraining role during compaction, influencing cell shape, cell organization and the time at which compaction takes place.


Critical analysis of thoracotomies performed in the emergency room in 10 years.
To conduct a critical analysis of thoracotomies performed in the emergency rooms. We analyzed mortality rates and survival as outcome variables, mechanism of injury, site of injury and anatomic injury as clinical variables, and gender and age as demographic variables of patients undergoing thoracotomy in the emergency room after traumatic injury. Of the 105 patients, 89.5% were male. The average age was 29.2 years. Penetrating trauma accounted for 81% of cases. The most common mechanism of trauma was wound by a firearm projectile (gunshot), in 64.7% of cases. Patients with stab wounds (SW) accounted for 16.2% of cases. Overall survival was 4.7%. Survival by gunshot was 1.4%, and by SW, 23.5%. The ERT following blunt trauma showed a 100%mortality. The results obtained in the Emergency Hospital of Porto Alegre POA-HPS are similar to those reported in the world literature.


Species differences in the N-acetylation by liver cytosol of mutagenic heterocyclic aromatic amines in protein pyrolysates.
The N-acetylation of 3-amino-1-methyl-5H-pyrido[4,3-b]-indole (Trp-P-2) and other heterocyclic aromatic amine promutagens isolated originally from protein pyrolysates was investigated using liver cytosols from various animal species and acetyl-CoA as an acetyl donor. Marked species differences in the enzymatic N-acetylation activity of these heterocyclic amines were observed. The N-acetylation activity also varied among the substrates used. The N-acetylation of these heterocyclic amines by hepatic cytosols from all animal species used was much less than that of the non-heterocyclic aromatic amine carcinogen, 2-aminofluorene (2-AF): the N-acetylation of Trp-P-2 was more than one hundred times less than that of 2-AF. These results suggested that the metabolic activation pathway of these mutagenic heterocyclic amines is different from that of 2-AF. The hamster but not rat cytosol showed the ability to utilize N-hydroxy-2-acetylaminofluorene and 2-acetylaminofluorene as acetyl donor in the N-acetylation of Trp-P-2.


The nurse-patient relationship as a story of health enhancement in community care: A meta-ethnography.
To explore and improve our understanding of how nurse-patient relationships can enhance patients' health by synthesizing knowledge from published qualitative studies from both patients' and nurses' perspectives in community care. While primary research showing the health benefits of the nurse-patient relationship has been reported, this knowledge has not previously been synthesized. Meta-ethnography. A comprehensive search of five relevant databases, without year limitation, was completed. Inclusion criteria were: peer-reviewed studies exploring patient and/or nurse perspectives in community care settings, using a qualitative approach and published in English in any country. Noblit and Hare's meta-ethnographic approach. Ten primary studies published between 1997 - 2014 met the research objective and inclusion criteria and were appraised as high quality using CASP. Included studies reported similar findings and reciprocal translational analysis was possible. Six core themes were identified: entering the patient's world; trusting and telling; identifying different needs and uncovering change; patients becoming masters of their own health; patients experiencing health in illness; and nurses going the distance. The core themes were synthesized into a metaphor of "the nurse-patient relationship as a story of health enhancement", which illustrates the meaning of the "common story" they create together. The findings help us better understand how the nurse-patient relationship may enhance the patient's health, not only with regard to illness, physical condition and treatment but also physical, emotional, mental and social well-being. The nurse-patient relationship also has the potential to strengthen the patient's own resources towards maintaining health.


Identification of the intracytoplasmic region essential for signal transduction through a B cell activation molecule, CD40.
CD40 is a 45-kDa glycoprotein expressed on human B lineage cells. Anti-CD40 induces the proliferation of B cells and the extracellular region of CD40 is related to those of a certain kind of growth factor receptors. Therefore, it has been proposed that CD40 might be a receptor for a molecule involved in the growth regulation of B cells. The cDNA coding for CD40 was transfected into the murine B lymphoma cell line M12 and the murine thymoma cell line EL4. The growth of both M12 and EL4 transfectants expressing human CD40 was inhibited by anti-CD40. Phorbol 12-myristate 13-acetate (PMA) augmented the growth inhibitory effects of anti-CD40 on transfectants. The CD40 molecule was constitutively phosphorylated not only in human tonsil B cells but also in transfectants expressing CD40. PMA augmented the phosphorylation of CD40 in these cells. These results indicate that in spite of the growth inhibitory effect of anti-CD40, the augmentative effect of PMA is conserved in CD40+ transfectants and suggest that the transfectant might be useful for the study of signal transduction mechanism through CD40. To investigate which part of the CD40 molecule is important for signal transduction, transfectants expressing mutant CD40 cDNA were established and their growth response to anti-CD40 was evaluated. The mutant molecule, which had an Ala for Thr substitution at position 234, and the deletion mutants lacking Thr234 were inactive in growth signal transduction, indicating that Thr234 itself or the region around Thr234 is essential for signal transduction through CD40.