Stress and HPA-axis functioning in young people at ultra high risk for psychosis.
It is thought that hypothalamic-pituitary-adrenal (HPA) axis functioning mediates between the experience of stress and development of psychotic symptoms. This study aimed to evaluate this model in a cohort of young people at ultra high risk (UHR) of psychosis. Information about the experience of psychological symptoms and recent stressful experiences was obtained from 23 young people who met UHR criteria. Plasma samples were taken to assess cortisol and glucocorticoid receptor numbers, and an MRI scan was also performed. Plasma cortisol levels were significantly and positively correlated with the experience of 'hassles' but not with the experience of stressful life events. Significant positive associations were also found between plasma cortisol levels and level of depression and anxiety. No significant relationships were found between plasma cortisol level and global psychopathology, psychotic symptomatology, functioning or pituitary and hippocampal volumes. These results suggest that the number of hassles experienced by young people at UHR of psychosis could be an important factor in raising their cortisol levels, which might, in turn, affect the severity of depressive and anxiety symptoms. No other relationships were found between plasma cortisol levels and the experience of psychotic symptoms, functioning or hippocampal and pituitary volumes. These results indicate possible impairment in HPA-axis functioning in the early stages of psychotic illness, but further investigation of the relationships between these parameters is required.


Identification of the novel AML1 fusion partner gene, LAF4, a fusion partner of MLL, in childhood T-cell acute lymphoblastic leukemia with t(2;21)(q11;q22) by bubble PCR method for cDNA.
The AML1 gene is frequently rearranged by chromosomal translocations in acute leukemia. We identified that the LAF4 gene on 2q11.2-12 was fused to the AML1 gene on 21q22 in a pediatric patient having T-cell acute lymphoblastic leukemia (T-ALL) with t(2;21)(q11;q22) using the bubble PCR method for cDNA. The genomic break points were within intron 7 of AML1 and of LAF4, resulting in the in-frame fusion of exon 7 of AML1 and exon 8 of LAF4. The LAF4 gene is a member of the AF4/FMR2 family and was previously identified as a fusion partner of MLL in B-precursor ALL with t(2;11)(q11;q23), although AML1-LAF4 was in T-ALL. LAF4 is the first gene fused with both AML1 and MLL in acute leukemia. Almost all AML1 translocations except for TEL-AML1 are associated with myeloid leukemia; however, AML1-LAF4 was associated with T-ALL as well as AML1-FGA7 in t(4;21)(q28;q22). These findings provide new insight into the common mechanism of AML1 and MLL fusion proteins in the pathogenesis of ALL. Furthermore, we successfully applied bubble PCR to clone the novel AML1-LAF4 fusion transcript. Bubble PCR is a powerful tool for detecting unknown fusion transcripts as well as genomic fusion points.


Effect of recombinant human tissue inhibitor of matrix metalloproteinase-1 in mandibular distraction osteogenesis in rabbits: a computed tomographic study.
Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), are responsible for the controlled degradation of collagen in bone. We studied the long-term stability of the regenerated bone formed by distraction osteogenesis, and the effect of recombinant human TIMP-1 on the remodelling of bone formed by mandibular distraction osteogenesis in rabbits. Nine rabbits were subjected to distraction osteogenesis of the mandible and divided into three groups: a control group with no collagen implanted; a sham-control group with a collagen sheet implanted; and an experimental group with a collagen sheet impregnated with rhTIMP-1 implanted. Computed tomograms were taken at weeks 4, 12, and 24 after distraction, and micro-computed tomograms and histological examinations were made at week 24. There was no significant resorption of regenerated bone at the site of distraction in any group after 6 months of consolidation, suggesting that the regenerated bone formed by distraction osteogenesis is stable. We found no obvious influence of rhTIMP-1 in the collagen sheet on the bony regenerate after 6 months of consolidation.


Clinical model of cost of bladder cancer in the elderly.
To develop a population-based clinical model of bladder cancer (BC) care costs and identify cost drivers. We retrospectively reviewed a cohort of 4863 patients with BC identified from the linked Surveillance, Epidemiology and End Results-Medicare database, aged at least 65 years and diagnosed between 1994 and 1996. We collected the records of Medicare reimbursements (a surrogate of costs) through 1998 and classified them into clinically relevant intervals and care types by disease invasiveness to derive the cumulative costs of care. We calculated the incremental resource use costs using sex and age-matched controls from a 5% general population sample and compared similarly matched patients with other cancer (OC). We inflated all costs to 2006 U.S. dollars. The annual cost of care for all patients with muscle-invasive BC (MIBC) was $35.72M (95% confidence interval $35.69M to $35.75M), 70% more than the $21.03M (95% confidence interval $21.00M to $21.05M) for patients with non-MIBC. The major cost drivers, regardless of disease stage, were diagnostic/surveillance and complications, accounting for up to 43% and 37% of BC care costs, respectively. Comorbidity-adjusted incremental annual resource costs per patient with MIBC were more than four times greater than those for patients with non-MIBC, similar to those of OC controls (P = 0.490-0.913), except for inpatient (P = 0.002) and hospice (P <0.001) costs, which were both statistically significantly lower. Annual adjusted incremental Medicare reimbursements totaled $36.3M for non-MIBC and $96.1 million for MIBC. The results of this study have indicated that a reduction of BC care costs could be realized with strategies inhibiting disease progression and reducing the occurrence and severity of complications.


Early morphological changes in the striated muscles in normal and dystrophic chickens.
Histological and histochemical analyses were performed on the anterior latissimus dorsi muscle (ALD, red muscle) and the posterior latissimus dorsi muscle (PLD, white muscle) in normal (line 412) and dystrophic chickens (line 413) from 19 day embryos to 6 weeks of age. PLD, the white muscle, in dystrophic chickens showed higher percentages of red and intermediate fibres than those of normal chickens during the early development of muscles. Increases of the oxidative enzyme activities and the numbers of NADH--TR formazan granules in the white fibres of PLD were already found at 1 week of age in dystrophic chicken. Fibre types, oxidative enzyme activities and NADH--TR formazan granules showed no differences in ALD between normal and dystrophic chickens. These results suggest that increases of oxidative enzyme activities and formazan granule numbers and incomplete fibre type differentiation in PLD of dystrophic chickens are early pathological processes in such birds.


A novel pathway for insurance-based breast reductions: A method for identifying appropriate surgical candidates.
Breast reductions are one of the most common plastic surgery procedures performed. The purpose of this study was to streamline the evaluation of patients requiring breast reduction by using a nurse practitioner (NP)-led class to funnel appropriate surgical candidates through the preoperative process. We performed a retrospective review of patients interested in breast reduction who enrolled in this class from March 2015 to August 2021. Of the 1310 unique patients enrolled in the initial class, 386 patients passed the initial screening and were scheduled with the NP, whereas 924 were screened out at this stage either for being an inadequate surgical candidate or not showing up for clinical visits (36.7%). An additional 185 were screened out after the consultation with NP for reasons such as lack of insurance coverage and no-show visits (20.2%). MD visits had a no-show rate of 7.08%. The decrease in no-show rates between the class-NP visit and the NP-MD visit were both significant (p < 0.001). There was no significant difference in gram estimates between providers and pathology (p = 0.5). In total, 171 patients underwent breast reduction (13.05% of the patients screened). The average time from class to surgery was 278.15 days, NP consultation to surgery was 171.48 days, and MD consultation to surgery was 59.51 days. Using a screening pathway allows for early identification of inadequate surgical candidates and therefore streamlines the screening process for optimized breast reduction candidates. Appropriate use of NP visits functions to streamline the funnel, thus decreasing the number of visits and no-show appointments for a surgeon.


Bacterial origins of human cell-autonomous innate immune mechanisms.
The cell-autonomous innate immune system enables animal cells to resist viral infection. This system comprises an array of sensors that, after detecting viral molecules, activate the expression of antiviral proteins and the interferon response. The repertoire of immune sensors and antiviral proteins has long been considered to be derived from extensive evolutionary innovation in vertebrates, but new data challenge this dogma. Recent studies show that central components of the cell-autonomous innate immune system have ancient evolutionary roots in prokaryotic genes that protect bacteria from phages. These include the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, Toll/IL-1 receptor (TIR) domain-containing pathogen receptors, the viperin family of antiviral proteins, SAMHD1-like nucleotide-depletion enzymes, gasdermin proteins and key components of the RNA interference pathway. This Perspective details current knowledge of the elements of antiviral immunity that are conserved from bacteria to humans, and presents possible evolutionary scenarios to explain the observed conservation.


House officers' specialist career choices and motivators for their choice- a sequential mixed-methods study from Malaysia.
Shortage and maldistribution of medical specialists hamper healthcare quality. The specialist career choices of house officers determines the future composition of healthcare systems. We studied house officers'' specialist career choices and motivators for their choice. We conducted online in-depth interviews among seven house officers using an interview guide developed based on a literature review. The transcripts were analyzed. Major themes were identified. A 33-item questionnaire was developed, and the main and sub-themes were identified as motivators for specialist career choice. An online survey was done among 185 house officers. Content validation of motivators for specialist choice was done using exploratory factor analysis. First, second and third choices for a specialist career were identified. Multinomial logistic regression analyses were done to determine the socio-demographic factors and motivators associated with the first choice. HOs perceived that specialist training opportunities provide a wide range of clinical competencies through well-structured, comprehensive training programs under existing specialist training pathways. Main challenges were limited local specialist training opportunities and hurdles for 'on-contract' HO to pursue specialist training. Motivators for first-choice specialty were related to 'work schedule', 'patient care characteristics', 'specialty characteristics', 'personal factors', 'past work experience', 'training factors', and 'career prospects.' House officers' first choices were specialties related to medicine (40.5%), surgery (31.5%), primary care (14.6%), and acute care (13.5%). On multivariate analysis, "younger age", "health professional in the family", "work schedule and personal factors", "career prospects" and "specialty characteristics" were associated with the first choice. Medical and surgical disciplines were the most preferred disciplines and their motivators varied by individual discipline. Overall work experiences and career prospects were the most important motivators for the first-choice specialty. The information about motivational factors is helpful to develop policies to encourage more doctors to choose specialties with a shortage of doctors and to provide career specialty guidance.


The incidence of lymph node metastasis in early gastric cancer according to the expanded criteria in comparison with the absolute criteria of the Japanese Gastric Cancer Association: a systematic review of the literature and meta-analysis.
Japanese criteria for curative endoscopic resection of early gastric cancer initially included nonulcerated, well-differentiated mucosal lesions ≤2 cm in diameter, known as the absolute criteria. Subsequently, these indications were expanded to include larger, ulcerated, and undifferentiated mucosal lesions as well as differentiated lesions with slight submucosal invasion. Whether patients meeting the expanded criteria can be managed safely without gastrectomy and lymph node dissection has been controversial. The risk of lymph node metastasis (LNM) in patients who met the expanded criteria is a critical factor in determining the best course of management for these patients. We comprehensively searched main reference databases for studies that included patients who underwent gastrectomy and lymph node dissection for early gastric cancer. A meta-analysis was conducted by using the random effects model. Relative risk reduction was used to compare the incidence of LNM in patients meeting the absolute criteria as compared with those meeting the expanded criteria. Twelve studies met the inclusion criteria, providing a total of 9798 patients. The incidence of LNM was 0.2% for patients who met the absolute criteria as compared with 0.7% for patients who met the expanded criteria. Analysis of the various components of the expanded criteria was conducted, revealing that the incidence of LNM for differentiated mucosal lesions ≤3 cm with ulceration and for differentiated mucosal lesions without ulceration, irrespective of size, was 16 of 2814 (0.57%), reference range (RR) 3.01; P = .02 and 8 of 3004 (0.27%), RR 1.69; P = .37, respectively, only marginally higher than the risk of LNM associated with the absolute criteria. In contrast, undifferentiated mucosal lesions ≤2 cm and differentiated lesions <3 cm with slight submucosal invasion had a significantly higher incidence of LNM in comparison with the absolute criteria (25/972 [2.6%], RR 6.79; P = .0004 and 8/315 [2.5%], RR 6.30; P = .004, respectively). Overall, expanding the indication for endoscopic resection to include mucosal nonulcerated differentiated lesions irrespective of size and differentiated mucosal ulcerated lesions <3 cm is justified with minimal increased risk in comparison to the absolute criteria. However, expanding the indication for undifferentiated lesions ≤2 cm and differentiated lesions with slight submucosal invasion (T1b) should be balanced with the risks of surgery, given the increased risk of LNM in these patients.


Psychometric assessment of the Japanese version of the Revised Fibromyalgia Impact Questionnaire: reliability and validity.
To assess the psychometric properties of the Japanese version of the Revised Fibromyalgia Impact Questionnaire (JFIQR) in fibromyalgia (FM) patients. The reliability and validity of the JFIQR were assessed using online data collected from Japanese FM patients. Reliability was evaluated based on test-retest reliability results and internal consistency; validity was evaluated on the basis of concurrent and known-group validity. A total of 105 patients completed the online questionnaire. Intra-class correlation coefficients for test-retest were 0.91 for the JFIQR total score with a range of 0.84-0.90 in three domains: function, overall impact and symptoms. Internal consistency results indicated a Cronbach's alpha of 0.90 for the total score with a range of 0.83 and 0.85 for the domains. Concurrent validity results showed that the total score was correlated to all external criteria (Japanese version of the Fibromyalgia Impact Questionnaire, Fibromyalgia Activity Scale-31, Medical Outcomes Study 36-item Short-Form health survey) from a moderate to strong degree with most indicating a strong correlation. Results of known-group validity showed that the JFIQR total score is capable of discriminating between FM and the other groups, such as rheumatic arthritis and no chronic pain (P < 0.0001 for all pairwise comparisons). The current psychometric assessment of the JFIQR demonstrated that it is a reliable and valid questionnaire in Japanese patients with FM. Usefulness of the JFIQR in clinical studies and medical practice for Japanese-speaking populations is expected.


The TOC159 null mutant of Arabidopsis thaliana is impaired in the accumulation of plastid lipids and phosphatidylcholine.
We used electrospray ionization tandem mass spectrometry to profile glycerolipids in the TOC159 null mutant of Arabidopsis, which is referred to as plastid protein import 2, or ppi2. The goal was to evaluate the impact of a defective atToc159 receptor in the accumulation of plastid lipids. The ppi2 mutant is severely impaired in the accumulation of monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG) and phosphatidylglycerol (PG), which are major components of the thylakoid membranes. Major molecular species of MGDG and DGDG are drastically decreased, which is consistent with our previous findings of decreased levels of hexadecatrienoic and linolenic acids. Under normal growth conditions, the ppi2 mutant accumulated significantly lower levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). In the cold-acclimated mutant, the amounts of PE and PI were similar to the wildtype level, which indicates that the ER pathway of lipid synthesis was functional in the mutant. The cold-acclimated ppi2 mutant accumulated increased amounts of phosphatidic acid (PA), which was mirrored by an increase in phospholipase Dα (PLDα) transcript levels. These data suggest that PLDα activity contributed to the accumulation of cold-induced PA in the ppi2 mutant. The accumulation of major molecular species in PA indicates that cold-induced PA originated from the degradation of both plastidial and extraplastidial lipids. Compared with the wildtype, the ppi2 mutant had a low double bond index and high acyl chain length, which is indicative of decreased membrane fluidity. Taken together, these data indicate that a defective atToc159 receptor severely impaired the plastid pathway of lipid synthesis, which negatively affected the synthesis and/or accumulation of PC.


The effects of sheet and network solid structures of similar TPMS scaffold architectures on permeability, wall shear stress, and velocity: A CFD analysis.
Triply periodic minimal surface (TPMS) is known mathematically as a surface with mean curvature of zero and replicated in three directions infinitely. Providing the pore combination in porous structures with surface connections, they provide large surface areas. This study aims to determine the effects of the network solid and sheet solid structures in the three different TPMS architectures on bone regeneration. Evaluation is made for Diamond, Gyroid, and I-WP structures, which are widely preferred architectures in terms of mechanical strength. Scaffolds are modeled as both network solid and sheet solid unit cells with similar porosities (60%, 70%, and 80%). Flow analyses are performed with the Computational Fluid Dynamics method to determine of potential for bone cell development of scaffolds. The permeability, wall shear stress on the surfaces, and the flow velocity distribution of the scaffolds are obtained with these analyses. The permeability value of 18 scaffolds is between the permeability values determined for trabecular bone. The permeability of network solid TPMS scaffolds for the same architectures is higher than sheet solid TPMS scaffolds due to the low pressures generated. The maximum wall shear stress in scaffolds decreases as porosity increases. Since the maximum wall shear stresses occur in less than 0.1% area on the scaffold surfaces, it is more appropriate to examine distribution of these stresses on the scaffold surfaces. Sheet solid structures within TPMS are more advantageous for biomechanical environments due to their greater surface area at similar porosities, wall shear stress, and permeability values.


Perforating artery flow velocity and pulsatility in patients with carotid occlusive disease. A 7 tesla MRI study.
Patients with carotid occlusive disease express altered hemodynamics in the post-occlusive vasculature and lesions commonly attributed to cerebral small vessel disease (SVD). We addressed the question if cerebral perforating artery flow measures, using a novel 7T MRI technique, are altered and related to SVD lesion burden in patients with carotid occlusive disease. 21 patients were included with a uni- (18) or bilateral (3) carotid occlusion (64±7 years) and 19 controls (65±10 years). Mean flow velocity and pulsatility in the perforating arteries in the semi-oval center (CSO) and basal ganglia (BG), measured with a 2D phase contrast 7T MRI sequence, were compared between patients and controls, and between hemispheres in patients with unilateral carotid occlusive disease. In patients, relations were assessed between perforating artery flow measures and SVD burden score and white matter hyperintensity (WMH) volume. CSO perforating artery flow velocity was lower in patients than controls, albeit non-significant (mean difference [95% confidence interval] 0.08 cm/s [0.00-0.16]; p = 0.053), but pulsatility was similar (0.07 [-0.04-0.18]; p = 0.23). BG flow velocity and pulsatility did not differ between patients and controls (velocity = 0.28 cm/s [-0.32-0.88]; p = 0.34; pulsatility = 0.00 [-0.10-0.11]; p = 0.97). Patients with unilateral carotid occlusive disease showed no significant interhemispheric flow differences. Though non-significant, within patients lower CSO (p = 0.06) and BG (p = 0.11) flow velocity related to larger WMH volume. Our findings suggest that carotid occlusive disease may be associated with abnormal cerebral perforating artery flow and that this relates to SVD lesion burden in these patients, although our observations need corroboration in larger study populations.


Bone bruises associated with acute ankle ligament injury: do they need treatment?
The aim of this systematic review is to analyse the current knowledge, incidence, relevance, and need for treatment of bone bruises associated with acute ankle ligament injury. A search was made of PubMed, OVID/Medline, Cochrane databases using the keyword "bone bruises" in combination with "ankle", "sprain", "management", "surgery", and "conservative treatment". No randomized controlled trials or prospective cohort studies were found. Only case series were retrieved. A critical appraisal for validity and usefulness of the studies revealed that the best level of evidence on this topic is represented by retrospective comparative studies. Nine studies evaluating the management of bone bruises associated with acute ankle ligament injuries were found. The clinical prognosis of bone bruises is generally good, with a normalization of MRI appearance usually within 6-12 months after trauma. Currently, there is no evidence that these lesions need specific treatment. Thus, the management of the concomitant ligament lesions is sufficient. Further research is necessary to successfully address the management of bone bruises, and more evidence is required to decide if these lesions need to be treated at all.


Travellers' diarrhoea.
It is estimated that approximately 30% to 70% of international travellers will develop diarrhoea during their travels or after returning home. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute mild-to-moderate diarrhoea in adults from resource-rich countries travelling to resource-poor countries? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 24 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (empirical), antibiotics plus antimotility agents, antimotility agents, bismuth subsalicylate, diet, oral rehydration solutions, and racecadotril for travellers' diarrhoea.


Cancer Cachexia and breast cancer stem cell signalling - A crosstalk of signalling molecules.
Cancer Cachexia is a condition characterized by the involuntary loss of lean body mass, a negative protein and energy balance, and systemic inflammation. This syndrome profoundly impacts the patient's quality of life and is linked to poor chemotherapy response and reduced survival. Despite multiple mechanisms being implicated in its development, and various cytokines believed to contribute to the persistent catabolic state, cachexia is still not fully recognized and is often left untreated. Cachexia is caused by altered metabolic adaptation and lack of anticactic therapy due to systemic cytokines promoting and fuelling cancer growth. The exact molecular mechanisms and clinical endpoints remain poorly defined. It has an occurrence rate of 30%-80%, accounting for 20% of total cancer mortality. Tumor cells remodel the microenvironment suitable for their proliferation, wherein they communicate with fibroblast cells to modulate their expression and induce tumor progressive cytokines. Several studies have reported its strong correlation with systemic cytokines that initiate and aggravate the condition. Plenty of studies show the prominent role of cancer-induced cachexia in pancreatic cancer, colon cancer, and lung cancer. However, limited data are available for breast cancer-induced cachexia, highlighting the need for studying it. Breast cancer stem cells (BCSCs) are a prominently explored area in breast cancer research. They are characterized by CD44+/CD24-/ALDH+ expression and are a focus of cancer research. They are a source of renewal and differentiation within the tumor environment and are responsible for progression, and chemotherapeutic resistance. The tumor microenvironment and its cytokines are responsible for maintaining and inducing their differentiation. Cytokines significantly impact BCSC development and self-renewal, stimulating or inhibiting proliferation depending on cytokine and environment. Pro-inflammatory mediators like IL-6, TNF-α, and IL-8 increase proliferation, promoting tumor growth. Experimental models and clinical studies have shown a direct relationship between cytokines and BCSC proliferation. Several of them seem to be interconnected as they initiate signalling down different pathways but converge at BCSC increase and tumor proliferation. This review highlights the common pathways between cachexia and BCSC signalling, to identify potential therapeutic targets that can aid both conditions.


Breast Cancer Immunology and Immunotherapy: Current Status and Future Perspectives.
Cancer immunology has gained renewed interest in the past few years due to emerging findings on mechanisms involved in tumoral immune evasion. Indisputably, immune edition is currently considered a critical hallmark of cancer. Basic research has revealed new targets which can be modulated in the clinical setting with new compounds and strategies. As recent evidence confirms, breast cancer (BC) is a complex and heterogeneous disease in which host immune responses play a substantial role. T-infiltrating lymphocytes measurement is suggested as a powerful new tool necessary to predict early BC evolution, especially in HER2-positive and triple negative subtypes. However, T-infiltrating lymphocytes, genomic platforms, and many other biomarkers in tissue and peripheral blood (e.g., regulatory T cells and myeloid-derived suppressor cells) are not the only factors being evaluated regarding their potential role as prognostic and/or predictive factors. Many ongoing clinical trials are exploring the activity of immune checkpoint modulators in BC treatment, both in the advanced and neoadjuvant setting. Although this field is expanding with exciting new discoveries and promising clinical results-and creating great expectations-there remain many uncertainties yet to be addressed satisfactorily before this long awaited therapeutic promise can come to fruition.


[Does the asymptomatic carriage of FV Leiden and FII prothrombin in heterozygous configuration represent the increased risk of thrombembolic complications during pregnancy, childbirth and postpartum?].
To evaluate the course of pregnancy and puerperium in asymptomatic carriers of FV Leiden and FII prothrombin mutation in heterozygous configuration in terms of risk of thrombembolic disease and late pregnancy complications. To evaluate whether global prophylactic LMWH administration already during pregnancy has brought some benefit to these women. Prospective study. From June 2007 to June 2011, we monitored the incidence of thrombembolic events (TED) and severe late pregnancy complications in 473 asymptomatic carriers of FV Leiden and FII prothrombin mutation in heterozygous configuration. We also compared the ongoing changes of commonly clinically available hemocoagulation tests. In selected women, we added to coagulation tests a thrombin generation test (TGA) and thrombin-antithrombin test (TAT). In 253 women (Group A), preventive LMWH application was introduced already during pregnancy. In 220 women (Group B), the application of LMWH was commenced as late as on the delivery day. In both groups application of LMWH continued during the puerperium. The incidence of TED in the whole group of carriers of thrombophylic mutations accounted for 0.19%. The incidence of severe late pregnancy complications was very low - 3%. Medians of the monitored parameters of the hemocoagulation in compared groups and 'healthy' controls did not show statistically significant differences at any stage of pregnancy, labor or end of puerperium, with the exception of the results of TAT test at the end of puerperium. No direct causal relationship has been established between asymptomatic carriage of Leiden and prothrombin mutation in heterozygous configuration and the occurrence of severe late pregnancy complications. These types of mutation represent only a slightly increased risk in terms of development of thrombophylic events. General LMWH prophylaxis during pregnancy is not indicated. However, individual careful monitoring of hemocoagulation changes and early detection of associated transient situations potentiating risk of thrombembolic events is desirable. Statistically significant differences in the TAT results between group A and B at the end of puerperium revealed that the recommended extended LMWH prophylaxis until the end of puerperium was not followed by a number of women who started the prophylaxis on the date of labor.


Functional requirement of tyrosine residue 429 within CD5 cytoplasmic domain for regulation of T cell activation and survival.
CD5 has been mainly described as a negative regulator of TCR and BCR signaling and recent evidence has shown an important role for this receptor in delivering pro-survival signals. However, the molecular mechanisms underlying these processes remain unresolved. TCR crosslinking leads to phosphorylation of three tyrosine residues within the cytoplasmic tail of CD5 (Y429, Y441 and Y463) leading to the recruitment of signaling molecules like PI3K, c-Cbl and RasGAP; nevertheless, the role of these residues in T cell survival has not yet been assessed. In this study, we show that alanine-scanning mutagenesis of such tyrosine residues, either singly or in combination, leads to an increased thymocyte cell death with or without α-CD3 stimulation. Remarkably, the T-cell death observed with each individual tyrosine mutant was Caspase 3-independent. Furthermore, Y429 mutation resulted in a hyper-phosphorylation of ERK suggesting that this tyrosine residue regulates cell survival through down modulation of TCR signaling. Mutation of Y441 or Y463 did not induce hyper-responsiveness to TCR activation, indicating that they promoted T-cell survival by a TCR signal-independent pathway. Our results show that three tyrosine-based domains within CD5 cytoplasmic tail promote T-cell survival through non-overlapping mechanisms. This study also reveals that Y429 domain of CD5, previously described as a "pseudo ITAM", is functionally an ITIM domain in T cells.


Three-dimensional computed tomography angiography of the internal carotid artery for preoperative evaluation of sinonasal lesions and intraoperative surgical navigation.
Three-dimensional computed tomographic angiography (3DCTA) demonstrates the spatial relationships of the internal carotid artery (ICA) and adjacent skull base. This imaging modality may be incorporated into intraoperative surgical navigation during endoscopic skull base surgery. The charts of patients who had undergone 3DCTA imaging between July 2002 and February 2005 were reviewed. For 3DCTA, 1 mm axial computed tomography (CT) scan images were obtained with simultaneous intravenous contrast bolus on a multidetector CT scanner (Somatom Sensation 16, Siemens, Munich, Germany). The CBYON Suite version 2.6 to 2.8 (Med-Surgical Services, Mountain View, CA) was also used for creating CTA images through its volume-rendering protocols. A total of 22 3DCTA studies were performed for diagnostic evaluation or preoperative planning. In 18 instances, the 3DCTA images were used during intraoperative surgical navigation. The specific indications for obtaining the 3DCTA study included neoplasm (11 cases), cerebrospinal fluid leak (3 cases), fibro-osseous lesion (2 cases), mucocele (2 cases), and other (4 cases). Images generated by 3DCTA facilitated the definition of the anatomic relationships between the ICA and skull base lesion. During intraoperative surgical navigation, the 3DCTA provided critical information about the ICA location and adjacent skull base anatomy in the operative field. 3DCTA is a useful means for assessing the ICA and its relationship to skull base lesions. Incorporation of 3DCTA into intraoperative surgical navigation facilitates the comprehension of operative field anatomy in the ICA region. As a result, this imaging technique, especially when combined with intraoperative surgical navigation, may extend the applications of minimally invasive endoscopic approaches to the skull base.


Albumin-neprilysin fusion protein: understanding stability using small angle X-ray scattering and molecular dynamic simulations.
Fusion technology is widely used in protein-drug development to increase activity, stability, and bioavailability of protein therapeutics. Fusion proteins, like any other type of biopharmaceuticals, need to remain stable during production and storage. Due to the high complexity and additional intramolecular interactions, it is not possible to predict the behavior of fusion proteins based on the behavior the individual proteins. Therefore, understanding the stability of fusion proteins on the molecular level is crucial for the development of biopharmaceuticals. The current study on the albumin-neprilysin (HSA-NEP) fusion protein uses a combination of thermal and chemical unfolding with small angle X-ray scattering and molecular dynamics simulations to show a correlation between decreasing stability and increasing repulsive interactions, which is unusual for most biopharmaceuticals. It is also seen that HSA-NEP is not fully flexible: it is present in both compact and extended conformations. Additionally, the volume fraction of each conformation changes with pH. Finally, the presence of NaCl and arginine increases stability at pH 6.5, but decreases stability at pH 5.0.


Abemaciclib Is Active in Preclinical Models of Ewing Sarcoma via Multipronged Regulation of Cell Cycle, DNA Methylation, and Interferon Pathway Signaling.
Ewing sarcoma (ES) is a rare and highly malignant cancer that occurs in the bone and surrounding tissue of children and adolescents. The EWS/ETS fusion transcription factor that drives ES pathobiology was previously demonstrated to modulate cyclin D1 expression. In this study, we evaluated abemaciclib, a small-molecule CDK4 and CDK6 (CDK4 and 6) inhibitor currently under clinical investigation in pediatric solid tumors, in preclinical models of ES. Using Western blot, high-content imaging, flow cytometry, ELISA, RNA sequencing, and CpG methylation assays, we characterized the in vitro response of ES cell lines to abemaciclib. We then evaluated abemaciclib in vivo in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models of ES as either a monotherapy or in combination with chemotherapy. Abemaciclib induced quiescence in ES cell lines via a G1 cell-cycle block, characterized by decreased proliferation and reduction of Ki-67 and FOXM1 expression and retinoblastoma protein (RB) phosphorylation. In addition, abemaciclib reduced DNMT1 expression and promoted an inflammatory immune response as measured by cytokine secretion, antigen presentation, and interferon pathway upregulation. Single-agent abemaciclib reduced ES tumor volume in preclinical mouse models and, when given in combination with doxorubicin or temozolomide plus irinotecan, durable disease control was observed. Collectively, our data demonstrate that the antitumor effects of abemaciclib in preclinical ES models are multifaceted and include cell-cycle inhibition, DNA demethylation, and immunogenic changes.


Risk factors and outcomes of cytomegalovirus infection in children post cord blood transplantation with focus on impact of graft-versus-host disease and immunosuppressants.
Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality post cord blood transplantation (CBT). It has been suggested that the graft-versus-host disease (GVHD) and immunosuppressants have an impact on CMV infection. This study evaluated the incidence, outcomes, and risk factors of CMV infection, while focusing on GVHD and the use of immunosuppressants, in 103 children who had received CBT. Among the patients, 92.2% were positive for CMV serology, while CMV antigenemia was observed in 68.9% and CMV disease developed in 26.2%. CMV enterocolitis was the most common, followed by retinitis and pneumonia. Patients with positive CMV serology and grade II to IV GVHD were independently associated with CMV antigenemia. Recurrent CMV antigenemia was observed significantly more frequently in patients with extensive chronic GVHD. Patients with CMV disease showed significantly worse overall survival, relapse-free survival, and non-relapse mortality than those without CMV disease. In conclusion, CMV infection is common post-CBT in countries with a high rate of CMV seropositivity in the general population and is related to worse outcomes. GVHD severity is associated with the development and recurrence of CMV infection. Thus, efforts need to be made to prevent CMV infection in children post-CBT.


TrkB agonist, 7,8-dihydroxyflavone, reduces the clinical and pathological severity of a murine model of multiple sclerosis.
7,8-Dihydroxyflavone (DHF), is a recently described TrkB agonist that readily crosses the blood brain barrier. We treated C57Bl/6 mice with MOG--induced EAE daily with DHF starting on the day of disease induction. Clinical severity of impairment was reduced throughout the course of disease. Pathological examination of brains and spinal cords on day 28 showed that DHF treatment increased the phosphorylation of TrkB and activated downstream signaling pathways including AKT and STAT3 and reduced inflammation, demyelination and axonal loss compared to EAE controls. DHF treatment duplicated the central nervous system effects of brain derived neurotrophic factor in the EAE.


Antimicrobial and cytotoxic capacity of pyroligneous extracts films of Eucalyptus grandis and chitosan for oral applications.
Chitosan films containing distilled pyroligneous extracts of Eucalyptus grandis (DPEC), characterized and developed by Brazilian Agricultural Research Corporation-Embrapa Temperate Agriculture (EMBRAPA-CPACT), were evaluated for antimicrobial activity against Candida albicans, Streptococcus mutans, and Lactobacillus acidophilus by direct contact test. Further, their capacity for the prevention of teeth enamel demineralization and cytotoxicity in vitro were also determined. The natural polymers were tested at different concentrations (1500-7500 µg mL-1) and the formulation of an experimental fluoride varnish with antimicrobial activity was evaluated by direct contact test, whereas cytotoxicity was analyzed through the colorimetric MTT assay. Preliminary data showed no statistically significant differences in cytotoxicity to NIH/3T3 cell line when DPEC is compared to the control group. On the other hand, the antimicrobial capacity and demineralization effects were found between the test groups at the different concentrations tested. Chitosan films containing distilled pyroligneous extracts of E. grandis may be an effective control strategy to prevent biofilm formation related to dental caries when applied as a protective varnish. They may inhibit the colonization of oral microorganisms and possibly control dental caries through a decrease in pH and impairment of enamel demineralization.


MADYMO simulation of children in cycle accidents: a novel approach in risk assessment.
Head injuries are a significant cause of death and injury to child cyclists both on and off the road. Current evaluations of the effectiveness of cycle helmets rely on simplified mechanical testing or the analysis of aggregated accident statistics. This paper presents a direct evaluation of helmet efficacy by using computational modelling to simulate a range of realistic accident scenarios, including loss of control, collision with static objects and vehicle impact. A 6-year-old cyclist was modelled (as a Hybrid III 6-year-old dummy), in addition to a typical children's bicycle and a vehicle using the MADYMO dynamics software package. Simulations were performed using ranges of cyclist position, cycle speed and vehicle speed with and without a helmet that meets current standards. Wearing a cycle helmet was found to reduce the probability of head injuries, reducing the average probability of fatality over the scenarios studied from 40% to 0.3%. Similarly, helmet wearing reduced the probability of neck injuries (average probability of fatality reduced from 11% to 1%). There was no evidence that helmet wearing increased the severity of brain or neck injuries caused by rotational accelerations; in fact these were slightly reduced. Similarly, there was no evidence that increased cycling speed, such as might result from helmet related risk compensation, increased the probability of head injury.


The effect of gastrin, secretin and prostaglandin F2 alpha on the lower esophageal sphincter of dogs after Nissen fundoplication.
The effect of gastrin, secretin and prostaglandin F2 alpha on the canine lower esophageal sphincter (LES) after Nissen fundoplication was investigated by esophageal manometry. The gastrin-stimulated LES pressure was significantly higher intraoperatively 2 and 4 weeks after operation than the preoperative stimulation pressure. On the other hand, the prostaglandin F2 alpha-stimulated LES pressure 2 weeks after operation did not differ significantly from the preoperative stimulation value. At 2 weeks after Nissen fundoplication the LES pressure before secretin injection was significantly higher than the preoperative value. However, the LES pressure after secretin injection did not differ significantly from the preoperative stimulation pressure. Therefore, it seems that exogenously administered gastrin, unlike prostaglandin F2 alpha, stimulates the antireflux mechanism after wrapping of the gastric fundus in the Nissen procedure. It was suggested that secretin reacts against the new muscular sphincter substitute created by wrapping of the gastric fundus in the Nissen procedure.


Synthesis and characterization of two novel lanthanide coordination polymers with an open framework based on an unprecedented [Ln(7)(micro(3)-OH)(8)](13+) cluster.
Two novel heptanuclear lanthanide clusters of the dicubane-like type [Ln(7)(micro(3)-OH)(8)](13+) (Ln = Ho (1), Yb (2)) were obtained via hydrothermal reaction, and as building blocks, they were formally assembled into porous three-dimensional networks through the linkage of 1,4-naphthalenedicarboxylate (1,4-NDA), forming first examples of porous lanthanide polymers with 1,4-NDA, [Ln(7)(micro(3)-OH)(8)(1,4-NDA)(6)(OH)(0.5)(Ac)(0.5)(H(2)O)(7)].4H(2)O (Ln = Ho, Yb). The coordinating water molecules and lattice water molecules are enclathrated in the cavities.


Control of the large renal vein in limited dissected space during laparoscopic nephrectomy: a simple and reliable method.
We describe our technique for large renal vein control in the limited dissected space during laparoscopic nephrectomy. This technique is a simple, inexpensive and reliable method, especially for large and short renal vein ligation.


Seafood sold in Sweden contains BMAA: A study of free and total concentrations with UHPLC-MS/MS and dansyl chloride derivatization.
β-N-Methylamino-l-alanine (BMAA) is a potential neurotoxin associated with the aquatic environment. Validated analytical methods for the quantification of both free and total concentrations of BMAA were used in an investigation of seafood purchased from different grocery stores in Uppsala, Sweden. The analysis was performed using ultra high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) and detection of BMAA as a dansyl derivate. The determined concentrations of free BMAA (after a simple trichloroacetic acid extraction) in mussels and scallops were up to 0.46 μg g-1 wet homogenate. The total BMAA (after hydrochloric acid hydrolysis) levels were between 0.29 and 7.08 μg g-1 wet mussel homogenate. The highest concentration of total BMAA was found in imported cooked and canned mussels which contained about ten times the quantity of BMAA measured in domestic cooked and frozen mussels. In this study it was also concluded that BMAA could be detected in seafood origin from four different continents. The risks associated with human exposure to BMAA through food are unknown today. However, the results of this study show that imported seafood in Sweden contain BMAA, indicating that this area needs more investigation, including a risk assessment regarding the consumption of e.g., mussels, scallops and crab.


Pramipexole in the treatment of Parkinson's disease: new developments.
The nonergot dopamine agonist pramipexole is an efficient and safe drug for the treatment of Parkinson's disease. Clinicians may favor pramipexole over other dopamine agonists because of its suggested higher tolerability with respect to peripheral dopaminergic side effects. Importantly, nonergot dopamine agonists such as pramipexole may not cause restrictive valvular heart disease and may therefore represent the first choice in patients with valvular lesions under treatment with ergot dopamine agonists. However, particular caution has to be exercised in younger Parkinson's disease patients with a shorter disease duration regarding the occurrence of sudden onset of sleep. In light of cost-effectiveness and quality-of-life issues, its final significance for the initial treatment of patients with early Parkinson's disease remains to be determined.


Rationally designed PKA inhibitors for positron emission tomography: Synthesis and cerebral biodistribution of N-(2-(4-bromocinnamylamino)ethyl)-N-[11C]methyl-isoquinoline-5-sulfonamide.
Protein kinase A (PKA) is an important signal transduction target for drug development because it influences critical cellular processes implicated in neuropsychiatric illnesses such as major depressive disorder. The goal of the present study was to develop the first imaging agent for measuring the levels of PKA with positron emission tomography (PET). By rational derivatization of 5-isoquinoline sulfonamides, it was found that the introduction of a methyl group to the sulphonamidic nitrogen on the known PKA inhibitors N-(2-aminoethyl)isoquinoline-5-sulfonamide (H-9, 1) and N-(2-(4-bromocinnamylamino)ethyl)isoquinoline-5-sulfonamide (H-89, 2), (yielding N-(2-aminoethyl)-N-methyl-isoquinoline-5-sulfonamide (4) and N-(2-(4-bromocinnamylamino)ethyl)-N-methyl-isoquinoline-5-sulfonamide (5), respectively) does not appreciably reduce in vitro potency toward PKA. We have facilitated the synthesis of 4 by reacting isoquinoline-5-sulfonyl chloride with N-methylethylenediamine (20% yield). Several techniques were used to thoroughly characterize 4 including multi ((1)H, (13)C and (15)N) NMR spectroscopy and X-ray crystallography. Compound 4 and 1-(4-bromophenyl)-1-propen-3-yl bromide were reacted to produce 5 in 16% yield. Compound 2 was reacted with [(11)C]CH(3)I to prepare N-(2-(4-bromocinnamylamino) ethyl)-N-[(11)C]methyl-isoquinoline-5-sulfonamide ([(11)C]5), with a decay-corrected radiochemical yield of 32%, based on [(11)C]CO(2). [(11)C]5 was produced with >98% radiochemical purity and 1130mCi/mumol specific activity after 40min (end of synthesis). Conscious rats were administered [(11)C] 5 and sacrificed at 5, 15, 30 and 60min after injection. Radioactivity from all excised brain regions was <0.2%ID/g at all time points. The modest brain penetration of [(11)C]5 may limit its use for studying PKA in the central nervous system.


The Inner Lives of Doctors: Physician Emotion in the Care of the Seriously Ill.
Elisabeth Kübler-Ross' seminal 1969 work, On Death and Dying, opened the door to understanding individuals' emotional experiences with serious illness and dying. Patient's emotions, however, are only half the story in the patient-physician relationship. In recent years physicians' emotional reactions have gotten more attention. These sometimes-unacknowledged emotions influence how we approach our work, including life and death decisions. This article reviews some of the main emotions physicians experience when caring for seriously ill and dying patients and the challenges physicians face in regulating their emotions in a professional setting. We also discuss some of the ways that physician emotion may influence medical decision-making and contribute to conflict. Attention to the emotional level of physician experience may promote better care.


LncRNA AGAP2-AS1 interacts with IGF2BP2 to promote bladder cancer progression via regulating LRG1 mRNA stability.
The long non-coding RNA (lncRNA) AGAP2-AS1 was implicated in tumorigenesis, yet with unclear mechanism in the development of Bladder Cancer (BCa). We collected the clinicopathological features and tissue samples of 45 patients with BCa in Xiangya Hospital. Expressions of AGAP2-AS1 and LRG1 were detected by RT-qPCR in BCa tissues and normal tissues as well as in BCa cells. The roles of AGAP2-AS1 and LRG1 were investigated by CCK-8, colony formation assay, transwell assays and tube formation assay. The subcellular localization of AGAP2-AS1 was detected by Fluorescence in situ hybridization. Bioinformatics method, RNA immunoprecipitation, RNA pull-down assay and Actinomycin D test were used to predict and identify the relationships between AGAP2-AS1, LRG1 and IGF2BP2. Xenografted tumors were produced to explore the function of AGAP2-AS1 in BCa in vivo. AGAP2-AS1 and LRG1 were highly upregulated in BCa. AGAP2-AS1 positively correlated with T stage, grade and vascular invasion, but negatively correlated with the survival of patients. Overexpressions of AGAP2-AS1 promoted proliferation, migration, invasion, tumor angiogenesis in vitro and tumor growth, metastasis in vivo, knockdown of AGAP2-AS1 exhibited the opposite effects. AGAP2-AS1 localized mainly in the cytoplasm. AGAP2-AS1 directly bound to IGF2BP2 protein to enhance LRG1 mRNA stability. Inhibition of BCa progression by AGAP2-AS1 knockdown may be reversed by LRG1 overexpression. AGAP2-AS1 can promote BCa progression and metastasis by recruiting IGF2BP2 to stabilize LRG1.


Induction and clinical utilization of lymphokine-activated killer cells in patients with gastrointestinal tract cancers.
In 18 patients with cancers of the gastrointestinal tract, lymphokine-activated killer (LAK) cell activity was studied and compared with that of healthy subjects. After cultivation with 10(3) iu/mL of recombinant interleukin-2, the cytotoxicity of patients' lymphoid cells was increased from 13.6 +/- 6.8% to 76.2 +/- 19.5% against Daudi cells and from 12.8 +/- 8.1% to 76.2 +/- 19.5% against K-562 cells. Based on these results, autologous LAK cells were given to patients. LAK cells injected into subdermal metastatic tumours demonstrated a significant inhibitory effect on tumour growth in comparison with that of control tumour nodules. Of four patients with metastatic tumours in the liver, to whom LAK cells were administered via the hepatic artery, tumour size was reduced by about 25% (minor response) in one patient, with a decrease of computerized tomography attenuation in the tumours occurring in the other three patients.


Developmental regulation of IgM secretion: the role of the carboxy-terminal cysteine.
B lymphocytes do not secrete IgM, and plasma cells only secrete IgM polymers. Here we show that both events are attributable to the tailpiece found at the carboxyl terminus of mus chains, and we specifically implicate Cys-575. Thus, if Cys-575 was mutated, IgM was secreted by B cells. Similarly, a mutant IgG containing a mus tailpiece became largely retained within the cell; secretion was restored upon mutation of the tailpiece cysteine. Removal of Cys-575 also allowed hypersecretion of monomeric IgM by plasmacytoma cells. Following further removal of Cmu1, heavy chains were secreted in the absence of light chains. Thus, in B and plasma cells, Cys-575 is involved both in the polymerization of IgM and in intracellular retention of unpolymerized intermediates.


Standards for reporting surveillance information in freedom from infection models by example of Trichinella in Canadian market hogs.
Freedom from infection modeling, using scenario trees, has become an established methodology and is well described in the literature. However, standards for organizing and reporting the surveillance information incorporated into such models are less developed. Canada has been routinely testing for Trichinella spiralis in market hogs in federally inspected slaughter plants since the late 1990s. By way of presenting our work on T. spiralis in Canadian hogs, we propose that information in surveillance models be organized in distinct categories, each with specific parameters and values that are thoroughly described and justified. The proposed categories are: (1) definitions for the objectives, (2) initial time period, (3) inputs, (4) data, (5) model settings, (6) outputs, and (7) validation. Having a standardized manner of reporting such studies will facilitate their validation and expedite their evaluation by experts in the field and their use in trade negotiations.


Studies on cytochrome c oxidase, II. The chemical constitution of a short polypeptide from the beef heart enzyme.
A low molecular weight (approximately 6000) polypeptide fraction was isolated from beef heart cytochrome c oxidase, consisting of three peptides with the N-terminal end groups isoleucine, phenylalanine and serine. The complete amino acid sequence of the serine component is described. From the chemical constitution, a site-specific cleavage from a precursor protein and a possible function in membrane penetration and complex formation of the oxidase is inferred.


Emodin affects biofilm formation and expression of virulence factors in Streptococcus suis ATCC700794.
Streptococcus suis (S. suis) is a swine pathogen and also a zoonotic agent. In this study, the effects of subinhibitory concentrations (sub-MICs) of emodin on biofilm formation by S. suis ATCC700794 were evaluated. As quantified by crystal violet staining, biofilm formation by S. suis ATCC700794 was dose-dependently decreased after growth with 1/2 MIC, 1/4 MIC, or 1/8 MIC of emodin. By scanning electron microscopy, the structural architecture of the S. suis ATCC700794 biofilms was examined following growth in culture medium supplemented with 1/2 MIC, 1/4 MIC, 1/8 MIC, or 1/16 MIC of emodin. Scanning electron microscopy analysis revealed the potential effect of emodin on biofilm formation by S. suis ATCC700794. The expression of luxS gene and virulence genes in S. suis ATCC700794 was investigated by quantitative RT-PCR. It was found that sub-MICs of emodin significantly decreased the expression of gapdh, sly, fbps, ef, and luxS. However, it was found that sub-MICs of emodin significantly increased the expression of cps2J, mrp, and gdh. These findings showed that sub-MICs of emodin could cause the difference in the expression level of the virulence genes.


Epidemiology and Pattern of Oral and Maxillofacial Trauma.
Maxillofacial trauma represents a serious public health problem and their epidemiology is extremely variable.The objective of the present study was to analyze and discuss the epidemiological characteristics of 2492 patients with oral and maxillofacial trauma over a 5-year period. This retrospective study was conducted at different hospitals of Xinjiang from 2012 to 2016. Data were collected for the cause of injury, age and gender distribution, frequency and type of injury, localization and frequency of soft tissue injuries, dentoalveolar trauma, facial bone fractures, presence of associated injuries, nerve injury, different treatment protocols. All the data were analyzed using statistical analysis that is chi squared test.Statistical analyses performed included descriptive analysis, chi square test, and logistic regression analyses. A total of 2492 maxillofacial trauma patients were seen in 1981 patients with a male to female ratio of 3.88:1. The age group 21 to 30 years accounted for the largest subgroup in both sexes. The most common etiology of the trauma was traffic accident, accounted for 41.8%. The mandible (31.97%) was the most common site of fracture followed by the zygoma (25.3%). The common type associated injuries was limb injury (27.5%), it was followed by brain (24.5%) and eye (21.4%) injuries. The common nerve injury was the facial nerve injury, accounting for 62.9%. The incidence of oral and maxillofacial trauma is related to gender, age, and the cause of trauma. Young adults are the most likely group (P < 0.05). Maxillofacial trauma is often associated with limb, craniocerebral, and eye injuries. Traffic accident is the main cause of maxillofacial injury (P < 0.5).


Inhibition of endosomal sequestration of basic anticancer drugs: influence on cytotoxicity and tissue penetration.
The basic drugs doxorubicin and mitoxantrone are known to be concentrated in acidic endosomes of cells. Here, we address the hypotheses that raising endosomal pH with the modifying agents chloroquine, omeprazole or bafilomycin A might decrease sequestration of anticancer drugs in endosomes, thereby increasing their cytotoxicity and availability for tissue penetration. Chloroquine, omeprazole and bafilomycin A showed concentration-dependent effects to raise endosomal pH, and to inhibit sequestration of doxorubicin in endosomes. Chloroquine and omeprazole but not bafilomycin A decreased the net uptake of doxorubicin into cells, but there was no significant effect on uptake of mitoxantrone. Omeprazole and bafilomycin A increased the cytotoxicity of the anticancer drugs for cultured cells, as measured in a clonogenic assay, whereas chloroquine had minimal effects on cytotoxicity despite reduced uptake of doxorubicin. Omeprazole but not chloroquine or bafilomycin A increased the penetration of anticancer drugs through multicellular layers of tumour tissue. We conclude that modifiers of endosomal pH might increase therapeutic effectiveness of basic drugs by increasing their toxicity and/or tissue penetration in solid tumours.


Hemocompatibility of poly(ether imide) membranes functionalized with carboxylic groups.
Materials for blood-contacting applications have to meet high requirements in terms to prevent thrombotic complications after the medical treatment. Surface induced thrombosis, e.g., after application of cardiovascular devices, is linked clearly to the activation of coagulation system and platelet adhesion and activation. The flat sheet poly(ether imide) membrane (PEI) was modified by binding of iminodiacetic acid (IDA) for different periods of time to obtain surfaces with carboxylic (-COOH) groups, namely PEI-1 (modified for 1 min) and PEI-2 (modified for 30 min). The successful binding of the ligands was monitored by thionin acetate assay. The physico-chemical characteristics of the materials were analyzed by SEM, AFM, water contact angle, and Zeta potential measurements. Hemocompatibility of the polymer materials was studied by analyzing the activation of coagulation system (plasma kallikrein-like activity) and platelet adhesion/activation by using immunofluorescence technique. The blood response to PEI membranes was compared to that of a commercial poly(ethylene terephthalate) (PET) membrane. Our results showed that the increase of the negative charges on the modified PEI membrane surfaces (number of -COOH groups) caused a higher contact activation of the coagulation system and a higher rate of platelet adhesion and activation compared to non-modified PEI. However, overall the hemocompatibility of all PEI membranes was higher than that of PET.


The role of transesophageal echocardiography in atrial fibrillation.
Transesophageal echocardiography (TEE) is very useful in the evaluation and management of selected patients with atrial fibrillation, primarily by clear visualization of left atrial appendage thrombus. Insights gained from two-dimensional and Doppler interrogation of the appendage include recognition of the association of dense spontaneous contrast and reduced mechanical appendage function with increased risk of thromboembolism. TEE-guided cardioversion has been shown to be safe and effective for a subset of patients, provided it is performed by experienced operators familiar with imaging the appendage and recognizing artifacts.


Maturation characteristics of Rubus pennsylvanicus fruit: are black and red the same?
Fruit of the blackberry, Rubus pennsylvanicus Poir. (Rosaceae), were examined to determine variation in maturation characteristics. Maturation timing and rate varied greatly among individual fruits, resulting in a bi-colored fruiting display comprised largely of two maturation stages, pre-ripe (salmon and scarlet) and ripe (dark brown and black). While ripe fruit were generally larger and heavier than pre-ripe fruit, exhibiting greater fresh and dry fruit weight, diameter, water content, and total seed weight, no significant differences were found in energy content, i.e. numbers of calories per gram pulp, or in pulp:seed ratio. The differences between ripe and pre-ripe fruit appear to be due largely to an increase in water content and seed weight with maturity. The fact that little energetic benefit accrues to the preferential selection of ripe fruit suggests that bi-colored Rubus displays may be considered to be unicolored.


Heterophoria measured with white, dark-grey and dark-red Maddox rods.
Heterophoria is defined as a deviation from orthovergence position when no fusional contours are provided. It has been suggested that darkening one eye effects the phoric angle between the two eyes. We tested this assumption by comparing the phoric angles with white, dark-grey and dark-red Maddox rods. In a first group of 14 subjects horizontal heterophoria was measured with white, dark-grey and dark-red Maddox rods. In a second group of 43 different subjects horizontal heterophoria was measured with white and dark-red Maddox rods. Subjects were asked to continually correct any perceived deviation, using Herschel prisms. Readings were taken after 1 min. Group 1 (n=14): No significant difference between white, dark-grey and dark-red Maddox rods (Friedmann test). Correlation between white and dark-grey Maddox rods r=0.97 (P<0.0001), slope of regression line 0.92 (95% confidence interval 0.78-1.06). Correlation between white and dark-red Maddox rods r=0.94 (P<0.0001), slope of regression line 0.67 (95% confidence interval 0.53-0.82). Group 2 (n=43): No significant difference between white and dark-red Maddox rods (Wilcoxon signed rank tests). Correlation r=0.96 (P<0.0001), slope of regression line 0.95 (95% confidence interval 0.87-1.03). Our study revealed no significant difference and a high correlation among the phoric angles obtained with white, dark-grey and dark-red Maddox rods. The close match suggests that darkening one eye does not effect the phoric angle between the two eyes.


Depression and incident cardiovascular disease among patients with chronic kidney disease.
Depression is associated with an increased risk of cardiovascular disease (CVD) and is prevalent among patients with chronic kidney disease (CKD). We aimed to identify the association of depression with incident CVD. We studied patients with CKD stages 2-4 enrolled in the Chronic Renal Insufficiency Cohort (CRIC) and excluded participants with preexisting CVD. The Cox proportional hazard model was used to examine the association between baseline depression [Beck's Depression Inventory (BDI) score ≥11] and incidence of CVD (cerebrovascular accident, myocardial infarction, heart failure, or peripheral artery disease). Models were adjusted for age, sex, race, estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (UACR), systolic and diastolic blood pressure, and 10-year estimated CVD risk. Among 2585 CRIC study participants, 640 (25%) patients had depression at study baseline. Compared to patients without depression, patients with depression were more likely to be women (56% vs. 46%), non-White (68% vs. 53%), with household income <$20,000 (53% vs. 26%), without a high school degree (31% vs. 15%), uninsured (13% vs. 7%), with lower eGFR (42 vs. 46 ml/min/1.73 m (Palmer et al., 2013 Jul)22), and with higher UACR (90 vs. 33 mg/g). In multivariate analyses, depression was associated with a 29% increased risk of developing CVD (adjusted hazard ratio 1.29, 95% confidence interval 1.03-1.62, p = 0.03). BDI (as a continuous variable) was associated with CVD (adjusted hazard ratio 1.017, 95% confidence interval 1.004-1.030, p = 0.012). Among patients with CKD stages 2-4 enrolled in CRIC without preexisting CVD, depression was associated with a 29% increased risk of incident CVD.


Variation in Clinical Presentation, Metabolic Profile, Hormonal Parameters and Inflammatory Markers in Polycystic Ovary Syndrome Women with and without Polycystic Ovary Morphology Appearance.
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with a spectrum of presentation. Studies have reported considerably different rates in terms of the incidence of polycystic ovary morphology (PCOM) in patients with PCOS with inconsistent results regarding the effects of PCOM in them. The aim of this study was to determine the differences in clinical presentation, metabolic profile, hormonal parameters and inflammatory markers in PCOS women with and without PCOM on ultrasonography (USG). A total of 70 PCOS women were recruited. To analyse the differences between various parameters, the patients were divided into two groups based on the presence or absence of PCOM on USG of the pelvis as per the Rotterdam criteria. A total of 37 patients had PCOM as per the diagnostic criteria for PCOS (Group 1), while 33 patients did not have PCOM on USG and were designated as Group 2. All participants underwent a detailed clinical evaluation and biochemical investigations, including high-sensitivity C-reactive protein, serum adiponectin, luteinising hormone, follicle-stimulating hormone, total testosterone and serum anti-Mullerian hormone. The homeostasis model assessment of IR (HOMA-IR) was calculated using standard equations. The mean and Standard deviation were computed for all continuous variables. Frequencies and proportions were calculated for categorical variables. Comparisons of the mean scores between the study groups were assessed using the Unpaired Student's t-test. The mean score of the subgroups was also compared using the unpaired Student's t-test. P < 0.05 was considered significant for all statistical inferences. The mean LDL and mean triglyceride were higher in Group 2, which was statistically significant (P = 0.004 and P ≤ 0.001, respectively). The mean hs-CRP was found to be higher in Group 2, which was statistically significant (P = 0.005). The mean AMH was higher in Group 1, which was statistically significant (P = 0.002). Group 1 had higher adiponectin levels, which was statistically significant (P = 0.04). The above findings suggest that patients without diagnostic PCO morphology have a worse metabolic profile compared to those with PCO morphology on USG. Obese patients without PCO morphology probably have a higher cardiovascular risk compared to obese patients with PCO morphology.


Incidence of Progression of Persistent Nondysplastic Barrett's Esophagus to Malignancy.
The risk of esophageal adenocarcinoma (EAC) in patients with non-dysplastic Barrett's esophagus (NDBE) is low, so there is debate over the role of ongoing surveillance for patients with NDBE. It is important to identify patients at low risk for progression. We assessed cancer risk based on the subsequent number of endoscopies showing persistence of NDBE in a nationwide study in the Netherlands. In a population-based study, patients with a first diagnosis of NDBE were selected from the Dutch nationwide registry of histopathology. We calculated incidence rates and incidence rate ratios (IRR) for high-grade dysplasia (HGD) and EAC to determine whether the number of endoscopies negative for dysplasia and the persistence of NDBE over time associate with progression to malignancy. We identified 12,728 patients with NDBE during 2003 and 2013. HGD or EAC developed in 436 patients (3.4%) during 64,537 person-years of follow up (median, 4.9 years). The rate of progression to HGD or EAC was 0.68 (95% CI, 0.61-0.74) per 100 person-years. In patients with 2 consecutive endoscopies showing NDBE, the rate of progression to HGD or EAC decreased to 0.55 (95% CI, 0.46-0.64) per 100 person-years (IRR, 0.72; 95% CI, 0.60-0.87). Overall, the incidence of HGD or EAC decreased by 14% for each year of progression-free follow-up (IRR, 0.86; 95% CI, 0.81-0.92). In a population-based study in the Netherlands, we found patients with stable NDBE to have a low risk of progression to HGD or EAC. These findings indicate that surveillance intervals might be lengthened or even discontinued in subgroups patients with persistent NDBE.


Evaluation of three-dimensional changes after sinus floor augmentation with different grafting materials.
The aim of this retrospective investigation was to assess the dimensional stability of different grafting materials after maxillary sinus floor augmentation with computed tomography (CT) scans. Two postoperative CT scans were available from 16 patients who had undergone maxillary sinus lift procedures. The first scan was made within a few days after the surgical intervention and the second one >6 months later. A total of 25 maxillary sinuses were augmented with different materials before implant insertion by lateral antrostomy in a staged approach. The volume of bone formation was calculated using the Somaris Sienet Magic View software. Based on volumetric measurements of the augmented domes derived from the image sections, shrinkage was about 26%. The mean of the augmented bone volume was 3.02 cm(3) (1.4-5.56 cm(3); SD+/-1.18 cm(3)) as determined in the first CT scan. The respective mean volume in the second CT scan amounted to 2.28 cm(3) (0.92-4.46 cm(3); SD+/-1.07 cm(3)). Within the limits of our descriptive and analytic study, the results indicate a significant reduction of the graft volume after maxillary sinus augmentation. Further prospective studies will have to evaluate the quantitative changes of different bone graft materials for maxillary sinus augmentation procedures in order to improve long-term implant stability.


Fatty acid pattern and cholesterol in skeletal muscle of men aged 22 to 73.
In order to examine the relationship between fatty acid distribution of skeletal muscle membranes and age, a needle biopsy was performed on the vastus lateralis muscle of 20 healthy, non-obese males, ranging in age from 22 to 73 years. The muscle sample was homogenized, centrifuged at 100,000 x g, and the resulting pellet was saponified and acidified. The fatty acids and cholesterol were removed by a single hexane extraction and analyzed by gas--liquid chromatography with flame ionization detection. All subjects regardless of age had no consistent differences in the fatty acid profiles and cholesterol composition in the tissue. Correlation coefficients indicated no significant relationship between the age of the individual and any of the analyzed lipids. The results of this study indicated that aging may not be reflected by gross changes in the composition of structural lipids in the cell.


Patient Characteristics Associated with the Development of Oral Lichen Planus in Two Provinces in Canada.
To understand the risk factors that may be associated with the development of oral lichen planus (OLP) and its progression. We conducted retrospective chart reviews of adult patients with OLP who presented to oral medicine and oral pathology clinics in 2 provinces between September 2016 and January 2020. Data regarding age, sex, disease duration, sites of involvement, comorbidities, medications, allergies, smoking, alcohol use, treatment and follow up were collected. Descriptive statistics were assessed. Among the 94 patients with OLP, mean age was 62 years and most were female (73%). Mean disease duration was 3.1 years. Hypertension, thyroid disorders and diabetes were present in 32%, 28% and 17% of patients, respectively. A significant proportion of patients reported a major surgical procedure (47%) as a preceding event and an additional 7% reported a preceding stressful life event. Three OLP patients (3%) developed squamous cell carcinoma or dysplasia. The mean disease duration for these patients was 4.06 years and the frequency of biopsy in our study was approximately 14%. Female sex, endocrine and immunological comorbidities, such as thyroid disease and diabetes, and psychological stress may play a role in the development of OLP in the Canadian population. A small percentage of patients may develop malignant transformation and, thus, require long-term monitoring.


The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease.
The severity of renal cystic disease in the major form of autosomal dominant polycystic kidney disease (PKD1) is highly variable. Clinical data was analyzed from 324 mutation-characterized PKD1 patients (80 families) to document factors associated with the renal outcome. The mean age to end-stage renal disease (ESRD) was 54 yr, with no significant difference between men and women and no association with the angiotensin-converting enzyme polymorphism. Considerable intrafamilial variability was observed, reflecting the influences of genetic modifiers and environmental factors. However, significant differences in outcome were also found among families, with rare examples of unusually late-onset PKD1. Possible phenotype/genotype correlations were evaluated by estimating the effects of covariants on the time to ESRD using proportional hazards models. In the total population, the location of the mutation (in relation to the median position; nucleotide 7812), but not the type, was associated with the age at onset of ESRD. Patients with mutations in the 5' region had significantly more severe disease than the 3' group; median time to ESRD was 53 and 56 yr, respectively (P = 0.025), with less than half the chance of adequate renal function at 60 yr (18.9% and 39.7%, respectively). This study has shown that the position of the PKD1 mutation is significantly associated with earlier ESRD and questions whether PKD1 mutations simply inactivate all products of the gene.


Glutamate-receptor-induced modulation of GABAergic synaptic transmission in the hippocampus.
There is a large body of evidence about the short- and long-term changes in GABAergic transmission in the hippocampus produced by the action of different endogenous neuromodulators and in particular neurotransmitters. Both intrinsic hippocampal cells and afferent fibres coming into the hippocampus from various parts of the CNS release substances that are capable of changing inhibitory transmission. This review surveys current understanding of the action of glutamate on the inhibitory transmission mediated in the hippocampus via GABA(A) receptors. Here we pay special attention to the molecular and cellular mechanisms leading to spatio-temporal changes of the glutamate concentration in the extracellular space and to the localization and identity of glutamate receptors involved in this direct modulation of inhibition.


A Child with elemental mercury poisoning and unusual brain MRI findings.
Mercury vapor poisoning is a serious and potentially fatal problem. Neurological manifestations involving the central nervous system are seen with chronic mercury intoxication. We present the case of a 10-year-old child who demonstrated acrodynia, seizures, and visual impairment following 20 days of exposure to elemental mercury at home. The initial blood mercury concentration was 27.7 microg/L (normal <2 microg/L) and the initial 24-hour urine mercury concentration was 34.4 microg/L (normal =10 microg/L). After 9 months of treatment with D-penicillamine, the patient's clinical condition, biochemical laboratory parameters, and mercury concentrations all returned to normal. The T2-weighted MRI images of the patient's brain initially showed multiple hyperintense lesions in cerebral white matter, left globus pallidus, and putamen, which also improved.


[A retrospective study of the impressions and psychic reactions experienced by patients in a traumatological intensive care unit (author's transl)].
30 persons who had been treated for an average of 22 days on a traumatological intensive care unit were asked to comment on their impressions and experiences. 80% of the patients had been in need of artificial respiration; but this had not unduly distressed them and they remembered it only vaguely. The major worry in 30% of the cases was awareness of their condition and the fear of permanent physical and mental disablement. 25% had greatly suffered from thirst. There was no mention that finding themselves in an intensive care ward, being dependent on a respirator or monitoring equipment or being disorientated had caused distress. None of them had seriously contemplated the possibility of his own death. The frequent visits by relatives were regarded as great comfort and help towards achieving mental equilibrium. All these critically ill persons were highly impressed by the constant and dedicated medical and nursing care they had received.


The human complement component C1R gene: the exon-intron structure and the molecular basis of allelic diversity.
Human C1r is a component of the complement system, which is a major mediator of innate immunity. In this study we investigated the exon-intron organization of the human C1R gene, which spans 11 kb from the initiation codon to the stop codon, and is very similar in exon-intron structure to the C1S gene. Six common and rare alleles, C1R*1, C1R*2, C1R*5, C1R*8, C1R*9, and C1R*13, were characterized by five mutations at amino acid positions 114, 135, 146, 167 and 244, in exons 4, 5 and 7 where the CUB1, EGF and CUB2 domains are encoded, respectively. A comparison with the cDNA of the mouse C1r gene showed that C1R*2is likely to be an ancestral allele. In addition, nine nucleotide substitutions and one length polymorphism were found in introns 2, 3, 4, 8 and 10.


Radiofrequency glow-discharge devices for direct solid analysis.
The enormous potential of radiofrequency glow discharges (rf-GD) as photon, atom, or ion sources, coupled to spectrometric techniques, for rapid direct analysis of almost any conductor, semiconductor, or insulating material with good in-depth resolution has been demonstrated world-wide. This outstanding performance has prompted a great effort to develop and characterise rf-GD for direct materials analysis in recent years. The state of the art of rf-GD coupled to atomic absorption spectrometry, optical emission spectrometry, and mass spectrometry for direct solid analysis is reviewed here. A description of the principles of operation of the rf-GD and attempts to model these discharges are also given. Rf-GD instrumentation, both developed at research laboratories and commercially available, is described. Several practical examples are given demonstrating the capabilities of these techniques for bulk and depth-profile analysis. Finally, the research gaps to be filled for full implementation of rf-GD spectrometric techniques in industry and research centres alike for materials science studies and technical development are discussed.


A rapid purification of T4 polynucleotide kinase using Blue Dextran-Sepharose chromatography.
A rapid batch procedure is described for purification of T4 polynucleotide kinase (ATP:5'-dephosphopolynucleotide 5'-phosphotransferase, EC 220.127.116.11) to near homogeneity using Blue Dextran-Sepharose chromatography. The enzyme preparation is sufficiently free of contaminating endonuclease and alkaline phosphatase activities to be suitable for radioactively labeling nucleic acids in vitro. Kinetic measurements indicate that the chromophore of Blue Dextran, Cibacron Blue F3GA, inhibits the activity of T4 polynucleotide kinase competitively with respect to single stranded DNA substrate and non-competitively with respect to the rATP substrate.


Anaerobic degradation of benzoate: batch studies.
Response of benzoate along with phenol to different anaerobic inocula has been investigated in batch reactors. In Phase I, the anaerobic biodegradability of benzoate and phenol were evaluated using (a) washed acclimatized granular sludge (WAGS) collected from a passive phenol fed bench-scale up-flow anaerobic sludge blanket reactor (UASBR) and (b) unacclimatized flocculent sludge (UFS) from a UASB based sewage treatment plant (STP). The effect of varying concentrations of benzoate has been investigated in Phase II using acclimatized granular sludge (AGS) from a bench-scale UASBR. Extent of degradation of benzoate was more than the phenol. Increasing benzoate COD from 2500 to 11,700mg/L, resulted in decrease in (i) rate constant, k from 0.79 to 0.11/d and (ii) ultimate biochemical methane potential (microb, g CH4-COD formed/g benzoate COD) from 84% to 60%. Temporal trend conforming to logistic S-curve indicated stressed conditions at higher benzoate concentration. Benzoate degradation was found to be sensitive to nature as well as quantity i.e. food to microorganism (F/M) of inocula used.


Effects of probiotic supplements on cognition, anxiety, and physical activity in subjects with mild and moderate Alzheimer's disease: A randomized, double-blind, and placebo-controlled study.
Probiotics have been suggested as an effective adjuvant treatment for Alzheimer's disease (AD) due to their modulating effect on the gut microbiota, which may affect the gut-brain axis. Therefore, we aimed to evaluate the effects of two different single-strain probiotics on cognition, physical activity, and anxiety in subjects with mild and moderate AD. Eligible patients (n = 90) with AD were randomly assigned to either of two interventions [Lactobacillus rhamnosus HA-114 (1015 CFU) or Bifidobacterium longum R0175 (1015 CFU)] or placebo group, receiving probiotic supplement twice daily for 12 weeks. The primary outcome of the study was cognitive function measured by using the two tests, namely, the Mini-Mental State Examination (MMSE) and the categorical verbal fluency test (CFT). Secondary outcomes included a performance in Activities of Daily Living (ADL), the Lawton Instrumental Activities of Daily Living (IADL) scale, and the Generalized Anxiety Disorder (GAD-7) scale. Linear mixed-effect models were used to investigate the independent effects of probiotics on clinical outcomes. After 12 weeks, MMSE significantly improved cognition (P Interaction < 0.0001), with post hoc comparisons identifying significantly more improvement in the B. longum intervention group (differences: 4.86, 95% CI: 3.91-5.81; P < 0.0001) compared with both the placebo and L. rhamnosus intervention groups (differences: 4.06, 95% CI: 3.11-5.01; P < 0.0001). There was no significant difference between the two intervention groups (differences: -0.8, 95% CI: -1.74 to 0.14; P = 0.09). In conclusion, this trial demonstrated that 12-week probiotic supplementation compared with placebo had beneficial effects on the cognition status of patients with AD.


[Transplantation of mesenchymal derived stem cells followed by G-CSF injection can reconstitute hematopoiesis of lethally irradiated BALB/c mice].
To explore the hematopoietic reconstitution potential of mesenchymal derived stem like cells. We transplanted bone marrow mesenchymal derived stem like cells into lethally irradiated BALB/c mice. Hematopoietic cells were derived from the non-adherent bone marrow cells 24 hours after initial culture while murine mesenchymal derived stem like cells from bone marrow of donor mice were cultured for 10 days before the transplantation. All mice of group 1 and 3 died in 7-8 days post irradiation following transplantation, while all the mice from group 2 and 4 survived. The time course of hematopoietic reconstitution was then observed. The peripheral blood and bone marrow cell count recovered in the MSC + G-CSF transplanted group and the BM transplanted group after 3 weeks. Interestingly, CFU-GM number in the MSC + G-CSF transplanted group increased significantly after 2 weeks and even more than that in the BM transplanted group after 3 weeks while as CFU-GM colony dropped 2 weeks after in the BM transplanted group. Spleen colony (CFU-S) number and size of the MSC + G-CSF transplanted group was significantly greater than the BM transplanted group. Furthermore, PCR analysis was performed using peripheral blood cells to determine if any male-derived cells were present. No male-derived cells were found in any of the mice from group 1 and 3. Y-chromosome-specific src gene was found to be dominant in the MSC + G-CSF transplanted group and the BM transplanted group by week 4 post transplantation. In addition, we demonstrated that induction with G-CSF lead to CFU-GM colony formation from MSC compartment in vitro. These results indicate that under stimulation of G-CSF, mesenchymal derived stem like cells might differentiate into hematopoietic primitive stem cells in vivo and have the capacity to re-establish hematopoiesis in lethally irradiated mice. This study should provide an alternative transplantation treatment for malignancy.


Perioperative mortality and associated factors in patients undergoing radical nephrectomy.
To determine the incidence and related factors of perioperative mortality associated with radical nephrectomy in patients with renal tumours in a tertiary hospital. We conducted a cross-sectional study that reviewed the medical records of patients undergoing radical nephrectomy between January 1, 2007 and December 31, 2011 in a tertiary university hospital (Cali, Colombia). We measured sociodemographic variables and factors that may be associated with perioperative mortality. The statistical analysis was performed using STATA. We analysed 57 patients who underwent radical nephrectomy, 54.4% of whom were male, whose ages ranged from 14 to 81 years. All tumours had a unilateral presentation; 96.5% of the tumours were solid renal lesions, and 3.5% were cystic lesions. The most frequent histological findings were clear cell (63.2%), papillary (8.7%) and chromophobe cell (5.2%) renal carcinoma. There were no complications in 27 (47.3%) of the patients. According to the Clavien-Dindo classification of surgical complications, 16 (28%) patients had minor (grades i and ii) complications and 9 (15.6%) had major (grades iii and iv) complications, with an overall perioperative mortality (grade v) of 8.7% (5 patients). The perioperative mortality at 30 days for patients with nonmetastatic renal carcinoma who underwent radical nephrectomy at a tertiary university hospital in Cali, Colombia, was 4.1% (2 patients).


Role of peroxidation in erythrocyte aging.
The role of membrane peroxidation in red cell aging was investigated by exposing rat erythrocytes to a peroxide-generating system of xanthine oxidase with hypoxanthine, and the resulting alterations were compared to those observed during in vivo aging. Erythrocyte incubation with peroxides decreased the activities of adenylate cyclase and protein kinase, enzymes which were found to be reliable markers reflecting differences between young and old cells. Membranes from age-separated erythrocytes were solubilized and subjected to electrophoresis on gradient polyacrylamide-sodium dodecyl sulfate gels. Electrophoretic patterns indicated that old erythrocytes contained higher amounts of several membrane proteins than young cells. These were proteins in bands 2.1 and 4.1, and proteins of molecular weight larger than 250,000. There was a relative increase in the amount of proteins in band 4.1 and the high molecular weight (greater than 250,000) proteins as a results of peroxidation. These studies demonstrate that cells incubated in vitro with a peroxide-generating system resemble senescent erythrocytes in membrane enzyme activities, cell density, and membrane protein composition. We propose that peroxidation plays an important role in red cell aging.


Irradiated lactic acid-stimulated tumour cells promote the antitumour immunity as a therapeutic vaccine.
Low pH and lactate accumulation are characteristic features of the tumour microenvironment. With our study finding that high concentrations of lactic acid can inhibit tumour growth, it is conceivable that the administration of lactic acid could promote antitumour immunity in the context of a tumour vaccine. To test this concept, we studied the antitumour effect of irradiated tumour cells stimulated with lactic acid in mouse xenograft models to potentially improve whole-cell tumour vaccines. In this study, we found that the effects of lactic acid-stimulated tumour cells on dendritic cells (DCs) included enhancing phagocytic function and stimulating maturation and aggregation. Moreover, lactic acid could potentiate the immunogenicity of an irradiated whole-tumour cell vaccine and thus inhibit tumour growth. We further verified that the antitumour immune response was mediated by CD8+ T cells. In addition, interferon-γ-expressing CD4+ and CD8+ T cell numbers increased in the spleen and lymph nodes of mice immunized with the irradiated lactic acid-stimulated cells. Furthermore, changes in the tumour microenvironment were also observed in this study. Our findings may be helpful for developing a new strategy for cancer therapy.


Mycelium-Like Networks Increase Bacterial Dispersal, Growth, and Biodegradation in a Model Ecosystem at Various Water Potentials.
Fungal mycelia serve as effective dispersal networks for bacteria in water-unsaturated environments, thereby allowing bacteria to maintain important functions, such as biodegradation. However, poor knowledge exists on the effects of dispersal networks at various osmotic (Ψo) and matric (Ψm) potentials, which contribute to the water potential mainly in terrestrial soil environments. Here we studied the effects of artificial mycelium-like dispersal networks on bacterial dispersal dynamics and subsequent effects on growth and benzoate biodegradation at ΔΨo and ΔΨm values between 0 and -1.5 MPa. In a multiple-microcosm approach, we used a green fluorescent protein (GFP)-tagged derivative of the soil bacterium Pseudomonas putida KT2440 as a model organism and sodium benzoate as a representative of polar aromatic contaminants. We found that decreasing ΔΨo and ΔΨm values slowed bacterial dispersal in the system, leading to decelerated growth and benzoate degradation. In contrast, dispersal networks facilitated bacterial movement at ΔΨo and ΔΨm values between 0 and -0.5 MPa and thus improved the absolute biodegradation performance by up to 52 and 119% for ΔΨo and ΔΨm, respectively. This strong functional interrelationship was further emphasized by a high positive correlation between population dispersal, population growth, and degradation. We propose that dispersal networks may sustain the functionality of microbial ecosystems at low osmotic and matric potentials.


Hope in the context of chronic musculoskeletal pain: relationships of hope to pain and psychological distress.
The cognitive model of hope suggests that people with high levels of hope are able to think about the ways to goals (pathways) and motivated to pursue those pathways to reach their goals (agency). We hypothesized that higher levels of hope would be related to lower levels of pain and less psychological distress (ie, anxiety and depression) and better adjustment. This study aims to examine the relationship, if any, between cognition of hope and chronic musculoskeletal pain. One hundred and six patients with chronic musculoskeletal pain were recruited by convenient sampling from 2 public hospitals in Hong Kong. We assessed the hope level, psychological distress, and health outcomes by psychometric inventories. Zero-order correlation results showed that hope was inversely associated with psychological distress (ie, anxiety and depression) and positively related to subjective self-efficacy. There was no significant relationship with severity of pain. Patients presented with longer duration of chronic musculoskeletal pain have higher hope level while pain developed after injury on duty have lower hope level. The findings of this cross-sectional study highlight the potential importance of hope in understanding adjustment to chronic musculoskeletal pain. Future longitudinal research could help reveal how hope and adjustment interact over the treatment of chronic pain cases.


Spatial distribution of fecal pollution indicators in sewage sludge flocs and their removal and inactivation as revealed by qPCR/viability-qPCR during potassium ferrate treatment.
Sludge reuse and utilization is one of important routines of disseminating fecal pollution to surface water and groundwater. However, it remains unclear the spatial distribution of fecal pollution indicators in sludge flocs and their reductions during sludge treatment processes. In this study, the abundances of fecal pollution indicators including cross-assembly phage (crAssphage), JC and BK polyomavirus (JCPyV, BKPyV), human adenovirus (HAdV), the human-specific HF183 Bacteroides (HF183) and Escherichia coli (EC) in soluble extracellular polymeric substances (S-EPS), loosely-bound EPS (LB-EPS), tightly-bound EPS (TB-EPS), and pellets of sludge flocs were determined, and the effect of potassium ferrate (PF) treatment on their removal and inactivation was investigated by using both qPCR and viability-qPCR. Results showed that all investigated indicators were detected in each fraction of sludge flocs. The PF treatment led to a great migration of indicators from sludge pellets to sludge EPS and some extent of their inactivation in each fraction of sludge flocs. The overall reductions of human fecal indicators in sludge determined by qPCR were 0-1.30 logs, which were 0-2 orders of magnitude lower than those of 0.69-2.39 logs detected by viability-qPCR, implying their inactivation by PF treatment to potentially alleviate the associated human health risks.


Estimating the number of granule cells in the dentate gyrus with the disector.
A practical example is given of how a newly developed stereological estimator of particle number, the disector, can be used to make estimates of neuron number in the dentate gyrus of rats. The estimates are free of biases related to lost caps, overprojection and assumptions about size, shape and orientation of the objects that are counted. The disector principle and the practical considerations relating to histological preparations and sampling are presented.


Correction to: Benefit-Cost Analysis of the Danish Sun Safety Campaign 2007-2015: Cost Savings from Sunburn and Sunbed Use Reduction and Derived Skin Cancer Reductions 2007-2040 in the Danish Population.
Abstract, Results, first sentence, which previously read: "The results were based on a reduction of 9000 skin cancer cases, saving €47 million of which €29 million were derived from sunburn reductions and €16 million from reductions in sunbed use."