Manipulation of components of the renin angiotensin system in renal proximal tubules fails to alter atherosclerosis in hypercholesterolemic mice.
Whole body manipulation of the renin-angiotensin system (RAS) consistently exerts profound effects on experimental atherosclerosis development. A deficit in the literature has been a lack of attention to the effects of sex. Also, based on data with gene-deleted mice, the site of RAS activity that influences lesion formation is at an unknown distant location. Since angiotensin (AngII) concentrations are high in kidney and the major components of the RAS are present in renal proximal tubule cells (PTCs), this study evaluated the role of the RAS in PTCs in atherosclerosis development. Mice with an LDL receptor -/- background were fed Western diet to induce hypercholesterolemia and atherosclerosis. We first demonstrated the role of AT1 receptor antagonism on atherosclerosis in both sexes. Losartan, an AngII type 1 (AT1) receptor blocker, had greater blood pressure-lowering effects in females than males, but equivalent effects between sexes in reducing atherosclerotic lesion size. To determine the roles of renal AT1a receptor and angiotensin-converting enzyme (ACE), either component was deleted in PTCs after weaning using a tamoxifen-inducible Cre expressed under the control of an Ndrg1 promoter. Despite profound deletion of AT1a receptor or ACE in PTCs, the absence of either protein did not influence development of atherosclerosis in either sex. Conversely, mice expressing human angiotensinogen and renin in PTCs or expressing human angiotensinogen in liver but human renin in PTCs did not change atherosclerotic lesion size in male mice. Whole-body AT1R inhibition reduced atherosclerosis equivalently in both male and female mice; however, PTC-specific manipulation of the RAS components had no effects on hypercholesterolemia-induced atherosclerosis.


Increasing incidence of melanoma among middle-aged adults: an epidemiologic study in Olmsted County, Minnesota.
To identify changes in the incidence of cutaneous melanoma over time in the fastest-growing segment of the US population-middle-aged adults. By using the Rochester Epidemiology Project resource, we identified patients aged 40 to 60 years who had a first lifetime diagnosis of melanoma between January 1, 1970, and December 31, 2009, in Olmsted County, Minnesota. The incidence of melanoma and overall and disease-specific survival rates were compared by age, sex, year of diagnosis, and stage of disease. Between 1970 and 2009, age- and sex-adjusted incidence increased significantly over time (P<.001) from 7.9 to 60.0 per 100,000 person-years, with a 24-fold increase in women and a 4.5-fold increase in men. Although not significant (P=.06), the incidence of melanoma increased with age. Overall and disease-specific survival improved over time, with hazard ratios of 0.94 (P<.001) and 0.93 (P<.001) for each 1-year increase in the year of diagnosis, respectively. Each 1-year increase in the age at diagnosis was associated with an increased risk of death from any cause (hazard ratio, 1.07; P=.01) but was not significantly associated with disease-specific death (P=.98). Sex was not significantly associated with death from any cause (P=.81) or death from disease (P=.23). No patient with malignant melanoma in situ died from disease. Patients with stage II, III, and IV disease were more than 14 times more likely to die from disease than were patients with stage 0 or I disease (P<.001). The incidence of cutaneous melanoma among middle-aged adults increased over the past 4 decades, especially in middle-aged women, whereas mortality decreased.


Autologous neutralizing antibodies to the transmitted/founder viruses emerge late after simian immunodeficiency virus SIVmac251 infection of rhesus monkeys.
While the simian immunodeficiency virus (SIV)-infected rhesus monkey is an important animal model for human immunodeficiency virus type 1 (HIV-1) infection of humans, much remains to be learned about the evolution of the humoral immune response in this model. In HIV-1 infection, autologous neutralizing antibodies emerge 2 to 3 months after infection. However, the ontogeny of the SIV-specific neutralizing antibody response in mucosally infected animals has not been defined. We characterized the kinetics of the autologous neutralizing antibody response to the transmitted/founder SIVmac251 using a pseudovirion-based TZM-bl cell assay and monitored env sequence evolution using single-genome amplification in four rhesus animals that were infected via intrarectal inoculations. We show that the SIVmac251 founder viruses induced neutralizing antibodies at 5 to 8 months after infection. Despite their slow emergence and low titers, these neutralizing antibodies selected for escape mutants that harbored substitutions and deletions in variable region 1 (V1), V2, and V4 of Env. The neutralizing antibody response was initially focused on V4 at 5 to 8 months after infection and then targeted V1/V2 and V4 by 16 months. These findings reveal a striking delay in the development of neutralizing antibodies in SIVmac-infected animals, thus raising questions concerning the suitability of SIVmac251 as a challenge strain to screen AIDS vaccines that elicit neutralizing antibodies as a means to prevent virus acquisition. They also illustrate the capacity of the SIVmac quasispecies to modify antigenic determinants in response to very modest titers of neutralizing antibodies.


Hepatic resection for colorectal metastasis; time to challenge the accepted doctrine.
The selection of patients for resection of colorectal liver metastasis (CRLM) is based around a set of established rules and principles, some of which date back to and have changed little since the mid 1980's. In this paper the authors challenge this accepted doctrine and describe the criteria used for selection of patients for surgery in their own centre, criteria which permit the inclusion of many more patients for potentially curative surgery. They go on to describe methods used to increase resectability and discuss their own results achieved for the resection of CRLM.


Frailty, Age, ASA Classification, and BMI on Postoperative Morbidity in Mandibular Fracture ORIF.
To assess how traditional, simple markers of health independently affect postoperative morbidity of mandibular fracture open reduction-internal fixations (ORIFs). Cohort study. National Surgical Quality Improvement Project (NSQIP) Database. The 2005 to 2017 NSQIP database was queried for patients who underwent mandibular ORIF. To control for the severity of the trauma, an additional "concurrent surgery" variable was created. A modified 5-item frailty index was calculated based on the following: presurgery-dependent functional status, chronic hypertension, diabetes mellitus, history of chronic obstructive pulmonary disease, and history of congestive heart failure. Among 1806 patients with mandibular ORIFs (mean age 34.8 ± 15.4 years), modified frailty index (mFI) was associated with 30-day medical complications (p < .001), reoperation (p < .001), and readmission (p = .005) on univariate analysis. Increased age was associated with prolonged hospitalization (p < .001) and medical complications (p < .001). The increased American Society of Anesthesiologists (ASA) score was associated with all endpoints (p ≤ .003), while increased body mass index (BMI) was associated with none. On multivariate analysis, only increased ASA was associated with any adverse event (reference: ASA 1; ASA 2, odds ratio [OR]: 2.17 [95% confidence interval, CI: 2.17-3.71], p = .004; ASA 3-4, OR: 3.63 [95% CI: 1.91-6.91], p < .001). Similarly, mFI and BMI were not independently associated with prolonged hospitalization (≥2 days) (p ≥ .015), but 65+ age (reference: 18-49; OR: 2.33 [95% CI: 1.40-3.86], p = .001) and ASA 3 to 4 groups (reference: ASA 1; OR: 3.26 [95% CI: 2.06-5.14], p < .001) were. ASA status and age are more useful modalities than mFI or BMI in predicting poor postoperative morbidity in mandibular ORIF. These simple metrics can assist with managing surgeons' expectations for mandibular ORIF patients.


Synthesis of pyrazolo[5,1-a]isoquinolines via a silver(I)-catalyzed reaction of (1-arylethylidene)hydrazides with N'-(2-alkynylbenzylidene)hydrazides.
A silver(I)-catalyzed reaction of (1-arylethylidene)hydrazides with N'-(2-alkynylbenzylidene)hydrazides is reported, which provides an efficient approach for the synthesis of pyrazolo[5,1-a]isoquinolines. During the reaction process, azo-alkene and isoquinolinium-2-yl amide acted as the key intermediates, which then underwent [3 + 2] cycloaddition and intramolecular rearrangement leading to the corresponding pyrazolo[5,1-a]isoquinolines. Azo-alkene would be formed in situ from (1-arylethylidene)hydrazide in the presence of I2 and TBHP, and isoquinolinium-2-yl amide would be generated in situ via a silver(I)-promoted 6-endo cyclization of N'-(2-alkynylbenzylidene)hydrazide. This transformation proceeds smoothly under mild conditions and tolerates a broad range of functional groups.


Leukemia associated mutant Wilms' tumor gene 1 protein promotes expansion of human hematopoietic progenitor cells.
The transcription factor Wilms' tumor gene 1 (WT1) is highly expressed in the majority of leukemias, suggesting a role in leukemogenesis. Acquired WT1 mutations are reported as an independent predictor of poor clinical outcome, and mutations resulting in deletion of the entire DNA-binding zinc-finger domain (WT1delZ), is the most common type. The aim of this study was to study cellular effects of WT1(delZ) that may contribute to an oncogenic phenotype. We found that expression of WT1(delZ) supported proliferation of human hematopoietic CD34(+) progenitor cells. Moreover, WT1(delZ) transduced cells expressed erythroid markers, including raised levels of STAT5, independently of addition of erythropoietin. At the global gene expression level, WT1(delZ) caused upregulation of genes related to cell division and genes associated with erythroid maturation, in the absence of added erythropoietin. Our results indicate that WT1(delZ) promotes cell proliferation and expansion of progenitor cells, consistent with a possible role in leukemogenesis.


[Vertigo: it all revolves around the physical exam].
Dizziness is a common complaint in an emergency department. True vertigo, characterized by subjective sensation of rotation of the subject or of objects around the subject, may be peripheral (85%) or central (15%). Patient's history and physical exam identify the etiology of vertigo in more than 70% of patients. Hallpike test is easily performed and crucial for the diagnosis of benign paroxysmal peripheral vertigo. Central vertigo should be suspected and brain imaging performed in the presence of neurological symptoms, in older patients, or when several risk factors for cerebrovascular disease are present.


Failed utopias and practical chemistry: the Priestleys, the Du Ponts, and the transmission of transatlantic science, 1770-1820.
Eighteenth-century events, replete with Dickensian dualities, brought two Enlightenment families to America. Pierre-Samuel du Pont and Joseph Priestley contemplated relocating their families decades before immigrating. After arriving, they discovered deficiencies in education and chemistry. Their experiences were indicative of the challenges in transmitting transatlantic chemistry. The Priestleys were primed to found an American chemical legacy. Science connected Priestley to British manufacturers, Continental chemists, and American statesmen. Priestley's marriage into the Wilkinson ironmaster dynasty, and Lunar Society membership, helped his sons apprentice, and befriend manufacturer-chemist Thomas Cooper. However, ideological persecution forced them from England. Priestley's plans for his sons to inherit Wilkinson's ironworks evaporated; in America, efforts to establish manufactories, colonies, farms, and a college miscarried. Cooper taught college chemistry, but his materialism provoked dismissals. The Du Ponts were unlikely founders of an industrial-chemistry empire. Du Pont's philosophy promulgated that agriculture, not industry, produced wealth. Eleuthère-Irénée apprenticed in France's gunpowder administration, however, plans for his succession died and director Antoine Lavoisier, a family friend, was executed. E.-I. and Du Pont's arrest precipitated relocation to America. Du Pont's utopian colony and schemes proved unrealistic. Nevertheless, E.-I.'s gunpowder manufactory-utilizing transatlantic contacts and privileged knowledge of advanced French chemistry-succeeded through practical application.


Congenital cystic polypoid rectal hamartoma in a newborn foal.
A neonatal foal with signs of rectal bleeding was diagnosed with an intraluminal rectal mass and intussusception on surgical exploration of the abdomen. Histologically, the mass consisted of cystic spaces lined by simple columnar epithelium with numerous goblet cells and was surrounded by thin bands of smooth muscle in a myxomatous stroma. Although the mass shared similarities with retrorectal cystic hamartoma (tailgut cyst) and juvenile polyps, described in human medicine, location and histologic findings were not entirely consistent with either condition.


A method for immunofluorescent demonstration of three coexisting neurotransmitters in rat brain and spinal cord, using the fluorophores fluorescein, lissamine rhodamine, and 7-amino-4-methylcoumarin-3-acetic acid.
Coexistence of neurotransmitters within single nerve fibers or terminals can be convincingly demonstrated by the use of multicolor immunofluorescence. The present study examined whether three-color immunocytochemical localization of coexisting neurotransmitters can be performed using the blue fluorophore AMCA. Spectrofluorometric examination of secondary antibodies conjugated with AMCA, fluorescein, and lissamine rhodamine showed that the peaks of excitation and emission were well separated and that dots of AMCA-conjugated IgG dried on slides were not visible when viewed using microscope filters for rhodamine and fluorescein. These findings suggest that AMCA might be suitable for three-color immunofluorescence. The usefulness of AMCA for triple labeling was tested directly by staining sections of rat brainstem and spinal cord for serotonin (5HT), substance P (SP), and either enkephalin (ENK) or prepro-thyrotropin-releasing hormone 160-169 (ppT), a marker peptide for thyrotropin-releasing hormone. Triple labeling for 5HT, SP, and ppT was observed in both brainstem and spinal cord but was only very rarely observed for 5HT,SP, and ENK. No evidence was found for artifactual triple labeling, although false negatives appeared to be possible in some circumstances. We conclude that AMCA can be combined with fluorescein and lissamine rhodamine for three-color immunofluorescent studies of coexisting neurotransmitters. In addition, the coexistence of 5HT with ENK appears to be much less common than the coexistence of 5HT with either SP or ppT.


Splicing modulation therapy in the treatment of genetic diseases.
Antisense-mediated splicing modulation is a tool that can be exploited in several ways to provide a potential therapy for rare genetic diseases. This approach is currently being tested in clinical trials for Duchenne muscular dystrophy and spinal muscular atrophy. The present review outlines the versatility of the approach to correct cryptic splicing, modulate alternative splicing, restore the open reading frame, and induce protein knockdown, providing examples of each. Finally, we outline a possible path forward toward the clinical application of this approach for a wide variety of inherited rare diseases.


Nucleolar organizer regions: their significance in the maturation of the gut-associated lymphoid tissue.
Nucleolar organizer regions (NORs) are important for regulating protein synthesis. Our study points towards the possibility of determining gut-associated lymphoid (GAL) cell proliferation and maturation in fetuses from ten to 35 weeks of gestation by means of the Argyrophilic (Ag) staining for NORs. This technique was performed on paraffin-embedded small intestine and mesentery tissue sections from 30 fetuses at the 10th, 14th, 15th, 19th, 20th, 23rd, 31st, and 35th week of gestation. Our results showed that there was no statistically significant difference concerning the mean AgNOR values, between GAL cells and mesentery lymphoid cells (2.81 +/- 0.63 to 2.63 +/- 0.71; p > 0.1), from ten to 15 weeks' gestation. In this specific period, the lymphoid cells first appear and Peyer's patches are formed in the small intestinal mucosa. In contrast, in fetuses from 19 to 35 fetal weeks NOR counts were statistically significantly greater in GAL cells than in fetuses from ten to 15 gestational weeks (as compared to NOR counts in GAL cells in fetuses at an earlier fetal age) (3.28 +/- 0.73 to 2.81 +/- 0.63). Mean AgNOR values in mesentery lymphoid cells remained unchanged (2.62 +/- 0.57) (p < 0.001). In conclusion, increasing protein synthesis from the 19th till the 35th week of gestation is indicative of immune system maturation, given that at the same time GAL cells become fully mature. Mesentery lymphoid cells pass (migrate) to the small intestinal mucosa from the bloodstream, and they form the whole out-associted lymphoid tissue (GALT) organ (Peyer's patches). The lymphatics associated with mucosa associated lymphoid tissue (MALT) are all efferent; it seems that during fetal life due to genetically determined factors, draining vessels operating as afferent lymphatics at that time, change to efferent (where the immunological response is greatly amplified) as embryonal life progresses.


[Treatment of refractory malignant lymphomas with cisplatin, vinblastine, and bleomycin].
Eighteen patients with advanced malignant lymphoma resistant to previous chemotherapy were treated with combination chemotherapy consisting of cisplatinum, vinblastine and bleomycin. Ten patients (55%) responded (two complete remissions and eight partial). The median survivaL time of patients responding was 15 weeks which was better that the one in patients with no response (3 weeks). Toxicity was mild. We believe that the use of cisplatinum could be useful in patients with refractory malignant lymphoma in combination with other drugs.


Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners.
Systemic sclerosis (SSc) is a rare disabling autoimmune disease with a similar mortality to many cancers. Two randomized controlled trials of autologous hematopoietic stem cell transplantation (AHSCT) for SSc have shown significant improvement in organ function, quality of life and long-term survival compared to standard therapy. However, transplant-related mortality (TRM) ranged from 3-10% in patients undergoing HSCT. In SSc, the main cause of non-transplant and TRM is cardiac related. We therefore updated the previously published guidelines for cardiac evaluation, which should be performed in dedicated centers with expertize in HSCT for SSc. The current recommendations are based on pre-transplant cardiopulmonary evaluations combining pulmonary function tests, echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic testing, initiated at Northwestern University (Chicago) and subsequently discussed and endorsed within the EBMT ADWP in 2016.


Sensitivity and specificity of magnetic resonance imaging and computed tomography for the determination of the developmental state of cranial sutures and synchondroses in the dog.
During skull ontogenesis, growth centers in the skull base and calvarial bones allow gradual expansion of the cranial vault. Premature growth termination of cranial base synchondroses and/or calvarial sutures can result in devastating skull dysmorphologies. There is evidence to believe that a premature closure in one or more cranial growth centers contribute to the brachycephalic skull morphology in dogs. To provide a proof of concept for the non-invasive investigation of ontogenetic changes in cranial sutures and synchondroses in living dogs, we compared magnet resonance imaging (MRI) and computed tomography (CT) with histologic findings. Our aim was to determine the in vitro sensitivity and specificity for conventional clinical imaging methods in the assessment of cranial suture closure and synchondroses ossification in dogs. The evaluation of cranial base synchondroses in MRI had a sensitivity of up to 93.1% and a specificity of 72.7% dependent on the observer. The evaluation of cranial base synchondroses in CT had a sensitivity of 92.2% and a specificity of 86.4%. Suture assessment on MRI suture assessment had a sensitivity of 82.1% dependent on the observer and a specificity of 19.3%. CT suture assessment had a sensitivity of 85.1% and a specificity of 40.4% in dependence of the observer. Conventional cross-sectional imaging techniques (MRI and CT) allow reliable assessment of the open or closed state of synchondroses within the cranial base. In contrast CT and MRI are not suitable for a reliable assessment of the cranial sutures in dogs.


Oral exposure of mice to cadmium (II), chromium (VI) and their mixture induce oxidative- and endoplasmic reticulum-stress mediated apoptosis in the livers.
Health concerns regarding the environmental heavy metals in wildlife and humans have increased in recent years. We evaluated the effects of exposure of mice to low doses of cadmium (Cd), chromium (Cr) and their mixtures on oxidative- and ER-stress. Male adult mice were orally exposed to Cd (0.5 and 2 mg kg(-1) ), Cr (1 and 4 mg kg(-1) ) and binary Cd+Cr mixtures (0.25 + 05 and 1 + 2 mg kg(-1) ) daily for 36 days. We observed that the bioaccumulation of Cd and Cr in the liver in a dose-dependent manner, and the Cd and Cr contents in the 2 mg kg(-1) Cd and 4 mg kg(-1) Cr treated groups reached 2.43 and 3.46 µg g(-1) liver weight. In addition, treatments with 2 mg kg(-1) Cd, 4 mg kg(-1) Cr or their mixture (1 + 2 mg kg(-1) ) significantly decreased body and liver weights, increased the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and activities of catalase (CAT) and glutathione peroxidase (GPX) in the liver. Moreover, Cd and Cr exposures also elevated the transcription of the oxidative- and endoplasmic reticulum (ER)-stress related genes including Cat, Gpx, heme oxygenase 1 (Ho-1), regulated protein 78 (Grp78), activating transcription factor 6 (Atf6) and proaoptotic CCAAT/-enhancer-binding protein homologous protein (Chop) in a dose dependent manner in the liver. And hepatic cytochrome c levels increased in all Cd, Cr or their mixture treated groups. Furthermore, the transcriptional status and the activities of Caspase 9 and Caspase 3 were increased significantly in the liver when exposed to high doses of Cd, Cr or their mixture. These results suggested that a long period exposure of mice to Cd or Cr has the potential to elicit oxidative- and ER-stress mediated apoptosis in their livers. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 693-705, 2016.


The autoinflammatory side of recurrent pericarditis: Enlightening the pathogenesis for a more rational treatment.
Recurrent pericarditis (RP) is a troublesome and debilitating complication of acute pericarditis. Although the etiopathogenesis of this condition remains unknown, an intricate overlap of autoimmune and autoinflammatory pathways has been hypothesized to explain its beginning and recurrence over time. The majority of cases are defined as "idiopathic", reflecting our awkwardness to unravel the intimate mechanisms of RP. Given the possible occurrence of anti-nuclear, anti-heart and anti-intercalated disk antibodies as well as the association with peculiar human leukocyte antigen haplotypes, an autoimmune contribution has been claimed to specify the nature of RP. However, the most innovative pathogenic scenario of RP has been conferred to the innate immune system, mainly involving neutrophils and macrophages that produce a large amount of interleukin (IL)-1 via inflammasome activation. The clinical resemblance of RP with autoinflammatory diseases that may be marked by symptomatic serositis, high fevers and strikingly increased inflammatory parameters further suggests a similar inflammasome-mediated pathogenesis. Aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of therapy in RP, whereas colchicine is recommended on top of standard anti-inflammatory therapy, due to its role in inhibiting the IL-1 converting enzyme (caspase 1) within the inflammasome as well as the release of additional pro-inflammatory mediators and reactive oxygen species. With regard to treatment of RP refractory to NSAIDs and colchicine, blockade of IL-1 is the most relevant advance achieved in the last decade: the outstanding effect of the short-acting IL-1 receptor antagonist anakinra has been first recognized in the pediatric population, giving a proof of its practical feasibility. Over a more recent time, a growing experience with anakinra deriving from both large and small studies has further confirmed that RP might be regarded as an IL-1-mediated disease. This review aims to provide a contemporary insight into the mechanisms leading to RP as well as into the most recent literature data showing the beneficial approach originating from IL-1 blockade in this intriguing disorder.


Isolated obstruction of the right ventricular infundibulum in a patient with Williams' syndrome.
Williams' syndrome is a rare condition that is associated with severe cardiovascular manifestations. We report a patient with Williams' syndrome who also has isolated obstruction of the right ventricular infundibulum, an association that, to the best of our knowledge, has not been previously reported.


CORRECTING FOR SAMPLING BIAS IN QUANTITATIVE MEASURES OF SELECTION WHEN FITNESS IS DISCRETE.
We show with a simulation that nonrepresentative sampling of two discrete fitness classes leads to biased estimates of selection. Systematic underestimation occurs if the selected class is overrepresented in the sample and overestimation if the unselected class is overrepresented. The bias is greater the stronger the selection intensity, the smaller the true fraction of individuals favored by selected, and the lower the sample size. We present a simple method that allows a posteriori statistical correction in cases of biased sampling given a separate estimate of the actual class representation, describe its practical implementation, and show that it works.


A microscopically calcified Meckel's diverticulum: a histopathological perspective of a case of both gastric and pancreatic mucosae.
A 2-year-old child presented with a 1-week history of abdominal pain and non-bilious vomiting. Upon examination, the abdomen was distended and faecal aspirate was noted from a nasogastric tube. Ultrasound scan and a failed air enema demonstrated intestinal intussusception warranting a surgical intervention. The intraoperative findings were of an ileocolic intussusception that was reduced and a Meckel's diverticulum (MD) was noted as a lead point necessitating resection with an end-to-end anastomosis. Histopathological analysis revealed a heterotopic MD containing both gastric and pancreatic mucosae with dystrophic calcification. MD is a pathologically diverse condition. The commonest histopathological picture in MD is that of an ectopic gastric mucosa at the terminal ileum. The histopathological analysis of this case demonstrated the interesting heterotopic results with calcification, which the histopathologist needs to be aware of when interpreting a surgical specimen with a clinical picture consistent with intussusception.


Brooding Rumination and Internalizing Symptoms in Childhood: Investigating Symptom Specificity in a Multi-Wave Prospective Study.
Specificity of brooding rumination as a cognitive vulnerability for anxiety and depression was examined using the tripartite theory as a framework. The three factors of the tripartite theory (negative affect, positive affect, and physiological hyperarousal) were included in the same structural equation model (latent growth curves) to test three competing hypotheses: brooding rumination as a depression-specific vulnerability (i.e., brooding uniquely predicts shared negative affect + specific positive affect), anxiety-specific vulnerability (i.e., brooding predicts shared negative affect + specific physiological hyperarousal), or shared risk vulnerability (i.e., brooding predicts negative affect, the shared tripartite component common to both anxiety and depression). Data from children in 2nd through 7th grades (N = 303) were collected in three waves over two years. Results revealed brooding to be uniquely associated with initial levels of negative affect and physiological hyperarousal, thus providing support for the anxiety-specific vulnerability. Results from the multigroup analysis confirmed that the relationship among these variables did not differ across sex. Longitudinal associations between brooding and the tripartite factors are also discussed.


Challenges in the Heterologous Production of Antibiotics in Streptomyces.
The fast growing genome databases provide us with a large number of so far unknown secondary metabolite biosynthetic gene clusters. A key method to study these gene clusters is their heterologous expression in an engineered host strain. Gene clusters derived from actinomycetes are usually expressed in a Streptomyces host strain to identify and investigate the corresponding compounds. However, heterologous expression is often accompanied with some challenges affecting the production rates of secondary metabolites. The first step is therefore the selection of a suitable expression vector and host strain. Once production has been established, there are several possibilities to improve compound yields either by media screens, by overexpression of regulatory or transport genes or by introduction of constitutive or inducible promoters. A surely important, but hitherto little studied factor is also the regulation of a heterologously expressed gene cluster by its host strain. This review gives a short overview on the chances and challenges provided by heterologous production of secondary metabolites in Streptomyces.


[Glomerular filtration and associated factors in hypertensive individuals treated at primary care level].
In Brazil, arterial hypertension (AH) constitutes one of the main risk factors for chronic kidney disease (CKD). The monitoring of glomerular filtration (GF) is recommended for the assessment of kidney function in hypertensive individuals, as GF decrease precedes symptom onset. To assess GF and its associated factors in hypertensive individuals. A cross-sectional study was carried out from January to June 2008 in 297 individuals with arterial hypertension (AH) with or without diabetes mellitus (DM), treated at a primary care facility in the city of São Luís, Maranhão. Patients older than 20 years and of both sexes were included in the study. Sociodemographic and nutritional status data, GF rate and microalbuminuria levels in 24-hour urine were assessed, as well as blood pressure, glucose and serum creatinine levels and a lipidogram. Mean age was 60.6 x 11.5 years, with a predominance of the female sex (75.1%), overweight/obesity (65.0%) and large waist circumference (60.6%). The prevalence of GF < 60 ml/min was 24.6% in the AH group without DM and 18.3% in the AH group with DM, with no significant difference. For the AH group without DM, there was an association only between reduced GF and age > 65 years, which remained after adjustment. For the AH group with DM, there was an association between reduced GF and age > 65 years, smoking habit and obesity. However, after the adjustment, age and smoking habit remained as associated factors. In these patients, the prevalence of GF < 60 ml/min was high and after the adjustment, only age > 65 years and smoking habit were shown to be factors associated to GF. This reinforces the need to systematically evaluate GF in hypertensive individuals, aiming at the secondary prevention of chronic kidney disease.


Landscape composition and configuration in the central highlands of Ethiopia.
Landscape dynamics are common phenomenon in the human-dominated environments whereby it can be observed that the composition and configuration between landscape elements change over time. This dynamism brings about habitat loss and fragmentation that can greatly alter ecosystem services at patch, class, and landscape levels. We conducted a study to examine composition and configuration of forested landscape in the central highlands of Ethiopia using satellite images of over a period of four decades, and FRAGSTAT raster dataset was used to analyze fragmentation. Our result showed five land use/land cover (LULC) types in the study area. Cultivated land and settlement land increased at the expense of forestland, shrubland, and grassland. Fragmentation analysis showed the number of patches increased for all LULC types, indicating the level of fragmentation and interspersion. Juxtaposition increased for shrubland, grassland, and cultivated lands and decreased for settlement and forestland resulting in the fragmentation and isolation of patches. The study of LULC along with fragmentation at the landscape level can help improve our understanding of the pace at which conversion of landscape elements is happening and the impacts on ecosystem services as studies of LULC are courser in nature and would not show how each land use is reducing in size, proximity and shape among other things that determine ecosystem services. Such type of studies in rural landscapes are very vital to consider appropriate land management policies for the landscape level by taking into account the interaction between each element for sustainable development. We recommend land managers, conservationists, and land owners for observing the roles of each patch in the matrix to maximize the benefits than focusing on a single element.


Sinapic Acid Promotes Browning of 3T3-L1 Adipocytes via p38 MAPK/CREB Pathway.
Sinapic acid is a plant-derived phenolic compound, which acts as an antioxidant, anticancer, and anti-inflammatory agent. Although sinapic acid is valuable in a variety of therapeutic applications, its role in the improvement of obesity-related metabolic disease is relatively unexplored. Brown-like adipocytes (beige adipocytes) are characterized by a high concentration of mitochondria and high expression of uncoupling protein 1 (UCP1), which has specific functions in energy expenditure and thermogenesis. This study assessed the browning effects of sinapic acid in 3T3-L1 adipocytes. We investigated the expression of beige marker genes in 3T3-L1 adipocytes treated with sinapic acid. Sinapic acid increased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and UCP1. Sinapic acid also promoted mitochondrial biogenesis by dose-dependently upregulating the oxygen consumption rate and enhancing the expression of representative subunits of oxidative phosphorylation complexes. In addition, treatment with p38 mitogen-activated protein kinase (MAPK) inhibitor and cAMP response element binding (CREB) inhibitor decreased the expressions of genes associated with thermogenesis, mitochondrial biogenesis, and oxidative phosphorylation. In summary, sinapic acid initiates browning 3T3-L1 adipocytes via the p38 MAPK/CREB signaling pathway. Thus, sinapic acid may have potential therapeutic implication in obesity.


Poly(2-oxazoline)-Based Polyplexes as a PEG-Free Plasmid DNA Delivery Platform.
The present study expands the versatility of cationic poly(2-oxazoline) (POx) copolymers as a polyethylene glycol (PEG)-free platform for gene delivery to immune cells, such as monocytes and macrophages. Several block copolymers are developed by varying nonionic hydrophilic blocks (poly(2-methyl-2-oxazoline) (pMeOx) or poly(2-ethyl-2-oxazoline) (pEtOx), cationic blocks, and an optional hydrophobic block (poly(2-isopropyl-2-oxazoline) (iPrOx). The cationic blocks are produced by side chain modification of 2-methoxy-carboxyethyl-2-oxazoline (MestOx) block precursor with diethylenetriamine (DET) or tris(2-aminoethyl)amine (TREN). For the attachment of a targeting ligand, mannose, azide-alkyne cycloaddition click chemistry methods are employed. Of the two cationic side chains, polyplexes made with DET-containing copolymers transfect macrophages significantly better than those made with TREN-based copolymer. Likewise, nontargeted pEtOx-based diblock copolymer is more active in cell transfection than pMeOx-based copolymer. The triblock copolymer with hydrophobic block iPrOx performs poorly compared to the diblock copolymer which lacks this additional block. Surprisingly, attachment of a mannose ligand to either copolymer is inhibitory for transfection. Despite similarities in size and design, mannosylated polyplexes result in lower cell internalization compared to nonmannosylated polyplexes. Thus, PEG-free, nontargeted DET-, and pEtOx-based diblock copolymer outperforms other studied structures in the transfection of macrophages and displays transfection levels comparable to GeneJuice, a commercial nonlipid transfection reagent.


Ionization and excitation of uranium in a hollow-cathode lamp.
The influence of different carrier gases (Ne, Ar, Kr, Xe), their pressure, and discharge current on the excitation and ionization of uranium atoms in a vapor generator of hollow-cathode design has been investigated by monitoring emission line intensities. From our measurements of line intensities as a function of the carrier gas we obtain an indication of the role of Penning collisions on the excitation of radiative levels in U II.


Immunogenomics: using genomics to personalize cancer immunotherapy.
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy. A T cell-dependent mechanism of cancer progression was discovered in 2012, providing a potential link to cancer immunotherapy. Since then, an antibody against cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), ipilimumab, and three programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, pembrolizumab (Keytruda), nivolumab (Opdivo), and atezolizumab (Tecentriq), were approved by the Food and Drug Administration (FDA) in the USA. In this review article, based on evidence that has been emerging in the literature over the last decade, we will discuss the basis for including genomic data in immunotherapy regimens, the current progress in identifying biomarkers targetable by immune checkpoint blockade, and the application of these therapies in modern oncology programs. Going forward, the clinical application of NGS in personalized oncology programs could include dose monitoring and adjustment or the development of individualized vaccines or other personalized therapies based on the mutational landscape. The continued identification of new neoantigens and the efficient mobilization of tumor-reactive lymphocytes in patients with cancer will promote the advancement of immunotherapy using personalized NGS-guided technologies.


The role of community mixing styles in shaping epidemic behaviors in weighted networks.
The dynamics of infectious diseases that are spread through direct contact have been proven to depend on the strength of community structure or modularity within the underlying network. It has been recently shown that weighted networks with similar modularity values may exhibit different mixing styles regarding the number of connections among communities and their respective weights. However, the effect of mixing style on epidemic behavior was still unclear. In this paper, we simulate the spread of disease within networks with different mixing styles: a dense-weak style (i.e., many edges among the communities with small weights) and a sparse-strong style (i.e., a few edges among the communities with large weights). Simulation results show that, with the same modularity: 1) the mixing style significantly influences the epidemic size, speed, pattern and immunization strategy; 2) the increase of the number of communities amplifies the effect of the mixing style; 3) when the mixing style changes from sparse-strong to dense-weak, there is a 'saturation point', after which the epidemic size and pattern become stable. We also provide a mean-field solution of the epidemic threshold and size on weighted community networks with arbitrary external and internal degree distribution. The solution explains the effect of the second moment of the degree distribution, and a symmetric effect of internal and external connections (incl. degree distribution and weight). Our study has both potential significance for designing more accurate metrics for the community structure and exploring diffusion dynamics on metapopulation networks.


Time scale of eutherian evolution estimated without assuming a constant rate of molecular evolution.
Controversies over the molecular clock hypothesis were reviewed. Since it is evident that the molecular clock does not hold in an exact sense, accounting for evolution of the rate of molecular evolution is a prerequisite when estimating divergence times with molecular sequences. Recently proposed statistical methods that account for this rate variation are overviewed and one of these procedures is applied to the mitochondrial protein sequences and to the nuclear gene sequences from many mammalian species in order to estimate the time scale of eutherian evolution. This Bayesian method not only takes account of the variation of molecular evolutionary rate among lineages and among genes, but it also incorporates fossil evidence via constraints on node times. With denser taxonomic sampling and a more realistic model of molecular evolution, this Bayesian approach is expected to increase the accuracy of divergence time estimates.


Physiological characterization of Mycobacterium sp. strain 1B isolated from a bacterial culture able to degrade high-molecular-weight polycyclic aromatic hydrocarbons.
The aim of this study was to further characterize a bacterial culture (VUN 10,010) capable of benzo[a]pyrene cometabolism. The bacterial culture, previously characterized as a pure culture of Stenotrophomonas maltophilia (VUN 10,010), was found to also contain another bacterial species (Mycobacterium sp. strain 1B), capable of degrading a similar range of PAH substrates. Analysis of its 16S rRNA gene sequence and growth characteristics revealed the strain to be a fast-growing Mycobacterium sp., closely related to other previously isolated PAH and xenobiotic-degrading mycobacterial strains. Comparison of the PAH-degrading characteristics of Mycobacterium sp. strain 1B with those of S. maltophilia indicated some similarities (ability to degrade phenanthrene and pyrene), but some differences were also noted (S. maltophilia able to degrade fluorene, but not fluoranthene, whereas Mycobacterium sp. strain 1B can degrade fluoranthene, but not fluorene). Unlike the S. maltophilia culture, there was no evidence of benzo[a]pyrene degradation by Mycobacterium sp. strain 1B, even in the presence of other PAHs (ie pyrene) as co-metabolic substrates. Growth of Mycobacterium sp. strain 1B on other organic carbon sources was also limited compared with the S. maltophilia culture. This study isolated a Mycobacterium strain from a bacterial culture capable of benzo[a]pyrene cometabolism. The Mycobacterium strain displays different PAH-degrading characteristics to those described previously for the PAH-degrading bacterial culture. It is unclear what role the two bacterial strains play in benzo[a]pyrene cometabolism, as the Mycobacterium strain does not appear to have endogenous benzo[a]pyrene degrading ability. This study describes the isolation and characterization of a novel PAH-degrading Mycobacterium strain from a PAH-degrading culture. Further studies utilizing this strain alone, and in combination with other members of the consortium, will provide insight into the diverse roles different bacteria may play in PAH degradation in mixed cultures and in the environment.


Emotion fingerprints or emotion populations? A meta-analytic investigation of autonomic features of emotion categories.
The classical view of emotion hypothesizes that certain emotion categories have a specific autonomic nervous system (ANS) "fingerprint" that is distinct from other categories. Substantial ANS variation within a category is presumed to be epiphenomenal. The theory of constructed emotion hypothesizes that an emotion category is a population of context-specific, highly variable instances that need not share an ANS fingerprint. Instead, ANS variation within a category is a meaningful part of the nature of emotion. We present a meta-analysis of 202 studies measuring ANS reactivity during lab-based inductions of emotion in nonclinical samples of adults, using a random effects, multilevel meta-analysis and multivariate pattern classification analysis to test our hypotheses. We found increases in mean effect size for 59.4% of ANS variables across emotion categories, but the pattern of effect sizes did not clearly distinguish 1 emotion category from another. We also observed significant variation within emotion categories; heterogeneity accounted for a moderate to substantial percentage (i.e., I2 ≥ 30%) of variability in 54% of these effect sizes. Experimental moderators epiphenomenal to emotion, such as induction type (e.g., films vs. imagery), did not explain a large portion of the variability. Correction for publication bias reduced estimated effect sizes even further, increasing heterogeneity of effect sizes for certain emotion categories. These findings, when considered in the broader empirical literature, are more consistent with population thinking and other principles from evolutionary biology found within the theory of constructed emotion, and offer insights for developing new hypotheses to understand the nature of emotion. (PsycINFO Database Record


Moving Fast-Scan Cyclic Voltammetry toward FDA Compliance with Capacitive Decoupling Patient Protection.
Carbon-fiber microelectrodes allow for high spatial and temporal measurements of electroactive neurotransmitter measurements in vivo using fast-scan cyclic voltammetry (FSCV). However, common instrumentation for such measurements systems lack patient safety precautions. To add safety precautions as well as to overcome chemical and electrical noise, a two-electrode FSCV headstage was modified to introduce an active bandpass filter on the electrode side of the measurement amplifier. This modification reduced the measured noise and ac-coupled the voltammetric measurement and moved it from a classical direct current response measurement. ac-coupling not only reduces the measured noise, but also moves FSCV toward compliance with IEC-60601-1, enabling future human trials. Here, we develop a novel ac-coupled voltammetric measurement method of electroactive neurotransmitters. Our method allows for the modeling of a system to then calculate a waveform to compensate for added impedance and capacitance for the system. We describe how first by measuring the frequency response of the system and modeling the analogue response as a digital filter we can then calculate a predicted waveform. The predicted waveform, when applied to the bandpass filter, is modulated to create a desired voltage sweep at the electrode interface. Further, we describe how this modified FSCV waveform is stable, allowing for the measurement of electroactive neurotransmitters. We later describe a 32.7% sensitivity enhancement for dopamine with this new measurement as well as maintaining a calibration curve for dopamine, 3,4-dihydroxyphenylacetic acid, ascorbic acid, and serotonin in vitro. We then validate dopamine in vivo with stimulated release. Our developed measurement method overcame the added capacitance that would traditionally make a voltammetric measurement impossible, and it has wider applications in electrode sensor development, allowing for measurement with capacitive systems, which previously would not have been possible.


[Exceptions to hygienic requirements of dwellings in building restoration and indemnity for abuses in Italy].
Building restoration represents a fundamental tool to combine the population needs for housing with soil saving. Old buildings offer great possibilities, if we consider that 20% of residential buildings in Italy have been constructed before the beginning of XX century. In order to understand the public health impact of exemptions from hygienic requirements of dwellings, as well as indemnity for abuses, the authors analyse the national legislation on this topic. There is a strong need to update health standards and to rationalize and simplify the regulations, as a fundamental tool for the protection of public health in indoor environment.


Tissue penetration of antifungal agents.
Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection.


Influence of size and charge of unstructured polypeptides on pharmacokinetics and biodistribution of targeted fusion proteins.
Alternative non-IgG binding proteins developed for therapy are small in size and, thus, are rapidly cleared from the circulation by renal filtration. To avoid repeated injection or continuous infusion for the maintenance of therapeutic serum concentrations, extensions of unfolded polypeptides have been developed to prolong serum half-life, but systematic, comparative studies investigating the influence of their size and charge on serum half-life, extravasation, tumor localization and excretion mechanisms have so far been lacking. Here we used a high-affinity Designed Ankyrin Repeat Protein (DARPin) targeting the tumor marker epithelial cell adhesion molecule (EpCAM) in a preclinical tumor xenograft model in mice, and fused it with a series of defined unstructured polypeptides. We used three different sizes of two previously described polypeptides, an uncharged one consisting of only Pro, Ala and Ser (termed PAS) and a charged one consisting of Pro, Ala, Ser, Thr, Gly, Glu (termed XTEN) and performed for the first time a precise comparative localization, distribution and extravasation study. Pharmacokinetic analysis showed a clear linear relationship between hydrodynamic radius and serum half-life across both polypeptides, reaching a half-life of up to 21 h in mice. Tumor uptake was EpCAM-dependent and directly proportional to half-life and size, showing an even tumor penetration for all fusion proteins without unspecific accumulation in non-target tissue. Unexpectedly, charge had no influence on any parameter, neither tumor nor tissue accumulation nor kidney elimination kinetics. Thus, both polypeptide types have a very similar potential for precise half-life modification and tumor targeting.


Exposure to Adverse Social Behavior in the Workplace and Sickness Presenteeism among Korean Workers: The Mediating Effects of Musculoskeletal Disorders.
Adverse social behavior (ASB) by colleagues or superiors in the workplace is considered highly stressful for workers in South Korea. The authors investigate the mechanism by which ASB reduces productivity (measured in terms of sickness presenteeism (SP)), by examining the potential mediating role of musculoskeletal disorders (MSDs). All data are derived from the fourth Korean Working Conditions Survey, which investigated a representative sample of the working population. The authors analyze their general characteristics (age, gender, income, and education), work-related factors (job type, occupational ergonomic risk, job resource, employment contract, work schedule, working hour, and job demand), and health-related factors (self-rated health and MSDs). The authors use a two-step regression analysis to estimate the direct effect of ASB on SP and the indirect effect of SP via MSDs. The authors find that MSDs mediate 16.7% of the total effect of ASB on SP. When employment type and job conditions are considered, the role of the mediating variable in the group with a permanent contract, no shift or night work, and high working time is greater than the counterpart of each variable. Various strategies are needed to address MSDs according to the working environment, which might help limit the negative impact of ASB on SP.


The Benefits and Challenges of Using Patient Decision Aids to Support Shared Decision Making in Health Care.
Shared decision making (SDM) and patient-centered care require patients to actively participate in the decision-making process. Yet with the increasing number and complexity of cancer treatment options, it can be a challenge for patients to evaluate clinical information and make risk-benefit trade-offs to choose the most appropriate treatment. Clinicians face time constraints and communication challenges, which can further hamper the SDM process. In this article, we review patient decision aids (PDAs) as a means of supporting SDM by presenting clinical information and risk data to patients in a format that is accessible and easy to understand. We outline the benefits and limitations of PDAs as well as the challenges in their development, such as a lengthy and complex development process and implementation obstacles. Lastly, we discuss future trends and how change on multiple levels-PDA developers, clinicians, hospital administrators, and health care insurers-can support the use of PDAs and consequently SDM. Through this multipronged approach, patients can be empowered to take an active role in their health and choose treatments that are in line with their values.


Immobilization and ethanol stress induce the same molecular response at the level of the cell wall in growing yeast.
The effect of immobilization on the cell wall of Saccharomyces cerevisiae cells was investigated in comparison with freely suspended batch grown cells. The pattern of mannoproteins released from the cell wall after Zymolyase digestion showed the presence of new mannoprotein species when cell growth takes place in a state of immobilization. The same result was obtained by exposure of freely suspended cells to a stressful concentration of ethanol, showing that two different adverse culture conditions induce a similar molecular response at the cell wall level.


Characterization of extended-spectrum β-lactamases (ESBLs)-producing Salmonella in retail raw chicken carcasses.
Extended-spectrum β-lactamases (ESBLs)-producing Salmonella is considered a serious concern to public health worldwide. However, limited information is available on ESBLs-producing Salmonella in retail chicken products in China. The objective of this study was to characterize ESBLs-producing Salmonella isolates from retail chickens in China. A total of 890 Salmonella isolates from retail chicken carcasses collected from 4 provinces were firstly screened for ESBLs-production phenotype via the double-disk synergy test method. A total of 96 (10.8%, n=890) ESBLs-producing Salmonella were identified and subjected to PFGE analysis, characterization for the presence of ESBLs encoding genes, transposons, carbapenemase and virulence genes. A total of 59 PFGE profiles were detected in these 96 isolates, among which 57.3% were found to harbor blaTEM-1, whereas 30.2%, 24.0%, 18.8% and 7.3% were carrying blaOXA-1, blaCTX-M-15, blaCTX-M-3 and blaPSE-1 genes, respectively. Moreover, 42 (43.8%) isolates co-carried 2 ESBLs-producing genes, and two (2.1%) isolates co-carried 3 genes. Furthermore, 24 (25.0%) ESBLs-producing isolates carried VIM and 10 (10.4%) carried KPC encoding genes that closely associated with carbapenems resistance. Eighty-eight isolates harbored transposons ranging from 4.2% for Tn903 to 76.0% for Tn21. Out of the 88 Salmonella that harbored transposons, 25%, 22.7%, 23.9%, 10.2% and 1.1% of isolates were found to carry 2, 3, 4, 5 and 6 transposons, respectively. The minimum inhibitory concentration (MIC) values for cephalosporins (ceftriaxone, cefoperazone and cefoxitin) to ESBLs-producing isolates were from 4 to 1024μg/mL, for nalidixic acid were from 64 to 512μg/mL, for fluoroquinolones (ciprofloxacin, levofloxacin and gatifloxacin) were from 4 to 256μg/mL. Twenty-nine virulence genes were detected in the 96 ESBLs-producing isolates with 2.1% harbored spvR (lowest) and 90.6% harbored marT and steB (highest). All isolates carried at least one virulence gene, 83.3% of the isolates co-carried ≥10, 17.7% co-carried ≥15, and 1.0% co-carried 23 virulence genes. Interestingly, 16.7% of the isolates resistant to >12 antibiotics tested and shown to carry >4 transposons and 10 virulence genes. Our findings indicated that ESBLs-producing Salmonella isolated from retail chicken meat in China were highly resistant to antibiotics, frequently harbored transposons, virulence genes, carbapenems hydrolysis enzymes and ESBLs encoding genes. These isolates can pose a significant public health risk.


British expert advice on diet and heart disease C. 1945-2000.
This chapter looks at the evolution over fifty years of government recommendations for reducing the risk of coronary heart disease amongst the British population. It also explores how non-governmental organisations such as the BMA established their own nutritional advice giving mechanisms and tried to influence such recommendations--and how networks of scientists constituted advisory committees. Scientists tended to favour recommendations which would lead to interventions within the scope of their own disciplines. It was also the case that consensus was lacking for a long while; this was only arrived at during the end of the period under consideration.


Fertility and Endometriosis.
Approximately 30% to 50% of women that have the diagnosis of endometriosis also struggle with infertility. Twenty five percent to 50% of women diagnosed with infertility also have endometriosis, but the endometriosis may not be severe enough to be the primary etiology of infertility. White women have been reported to be more likely than African American women to have endometriosis. In addition, risk factors for endometriosis include below average body mass index, smoking, and alcohol use. Below is a discussion regarding the various ways in which endometriosis decreases fecundity and also discusses potential outcomes of fertility treatments regarding endometriosis.


Influence of cell type and cell culture media on the propagation of foot-and-mouth disease virus with regard to vaccine quality.
Suspension culture of BHK cells allows large-scale virus propagation and cost-efficient vaccine production, while the shift to animal-component-free cell culture media without serum is beneficial for the quality and downstream processing of the product. Foot-and-mouth disease virus is still endemic in many parts of the world and high-quality vaccines are essential for the eradication of this highly contagious and economically devastating disease. Changes to the viral genome sequence during passaging in an adherent and a suspension cell culture system were compared and the impact of amino acid substitutions on receptor tropism, antigenicity and particle stability was examined. Virus production in suspension cells in animal-component-free media and in serum-containing media as well as in adherent cells in serum-containing media was compared. Infection kinetics were determined and the yield of intact viral particles was estimated in all systems using sucrose density gradient centrifugation. Capsid protein sequence alterations were serotype-specific, but varied between cell lines. But The A24-2P virus variant had expanded its receptor tropism, but virus neutralization tests found no changes in the antigenic profile in comparison to the original viruses. There were no differences in viral titer between a suspension and an adherent cell culture system, independent of the type of media used. Also, the usage of a serum-free suspension culture system promoted viral growth and allowed an earlier harvest. For serotype O isolates, no differences were seen in the yield of 146S particles. Serotype A preparations revealed a decreased yield of 146S particles in suspension cells independent of the culture media. The selective pressure of the available surface receptors in different cell culture systems may be responsible for alterations in the capsid coding sequence of culture-grown virus. Important vaccine potency characteristics such as viral titer and the neutralization profile were unaffected, but the 146S particle yield differed for one of the tested serotypes.


Biomechanical study of two-level oblique lumbar interbody fusion with different types of lateral instrumentation: a finite element analysis.
The aim of this study was to verify the biomechanical properties of a newly designed angulated lateral plate (mini-LP) suited for two-level oblique lumbar interbody fusion (OLIF). The mini-LP is placed through the lateral ante-psoas surgical corridor, which reduces the operative time and complications associated with prolonged anesthesia and placement in the prone position. A three-dimensional nonlinear finite element (FE) model of an intact L1-L5 lumbar spine was constructed and validated. The intact model was modified to generate a two-level OLIF surgery model augmented with three types of lateral fixation (stand-alone, SA; lateral rod screw, LRS; miniature lateral plate, mini-LP); the operative segments were L2-L3 and L3-L4. By applying a 500 N follower load and 7.5 Nm directional moment (flexion-extension, lateral bending, and axial rotation), all models were used to simulate human spine movement. Then, we extracted the range of motion (ROM), peak contact force of the bony endplate (PCFBE), peak equivalent stress of the cage (PESC), peak equivalent stress of fixation (PESF), and stress contour plots. When compared with the intact model, the SA model achieved the least reduction in ROM to surgical segments in all motions. The ROM of the mini-LP model was slightly smaller than that of the LRS model. There were no significant differences in surgical segments (L1-L2, L4-L5) between all surgical models and the intact model. The PCFBE and PESC of the LRS and the mini-LP fixation models were lower than those of the SA model. However, the differences in PCFBE or PESC between the LRS- and mini-LP-based models were not significant. The fixation stress of the LRS- and mini-LP-based models was significantly lower than the yield strength under all loading conditions. In addition, the variances in the PESF in the LRS- and mini-LP-based models were not obvious. Our biomechanical FE analysis indicated that LRS or mini-LP fixation can both provide adequate biomechanical stability for two-level OLIF through a single incision. The newly designed mini-LP model seemed to be superior in installation convenience, and equally good outcomes were achieved with both LRS and mini-LP for two-level OLIF.


[Analysis of amelogenesis imperfecta with abnormal tooth eruption caused by FAM83H mutation].
Objective: FAM83H is one of the major pathogenic genes of amelogenesis imperfecta (AI). Previous studies focused on the abnormal enamel development and mineralization caused by the mutations in FAM83H. Here we aimed to observe other effects of FAM83H mutations on tooth eruption besides AI through clinical case analysis. Methods: Published AI cases with FAM83H mutations were searched through PubMed database, and the characteristics of tooth eruption of each cases were counted and analyzed. The literature search range was from January 1, 2008 to February 28, 2023, using the keywords FAM83H and amelogenesis imperfecta. The included literature must provide the detailed radiographic imaging or dental eruption information of AI patients, as well as FAM83H gene mutation information. The basic clinical information, tooth phenotypes, and mutations of all the enrolled cases were collected and analyzed in order to find the characteristics of abnormal tooth eruption. Results: Among 45 papers about FAM83H related to AI, twenty meeting the inclusion criteria were selected, involving 50 AI patients carrying FAM83H mutations who had radiographic image data or the detailed description of tooth eruption. A total of 34 abnormal erupted teeth were from 12 patients (12/50, 24%), among which 85% (29/34) had clear eruption path without any eruption obstructions, either embedded (25/34, 74%) or partially erupted (4/34, 12%). Tooth position analysis found that abnormal eruption of canines and second molars accounted for the highest proportion, accounting for 38% (13/34) respectively. Conclusions: The mutations in FAM83H may lead to amelogenesis imperfecta as well as abnormal tooth eruption at specific tooth positions.


Exercise cardiac power and the risk of heart failure in men: A population-based follow-up study.
Little is known about exercise cardiac power (ECP), defined as the ratio of directly measured maximal oxygen uptake with peak systolic blood pressure during exercise, on heart failure (HF) risk. We examined the association of ECP and the risk of HF. This was a population-based cohort study of 2351 men from eastern Finland. The average time to follow-up was 25 years. Participants participated at baseline in an exercise stress test. A total of 313 cases of HF occurred. Men with low ECP (<9.84 mL/mmHg, the lowest quartile) had a 2.37-fold (95% confidence interval (95%CI): 1.68-3.35, p < 0.0001) hazards ratio of HF as compared with men with high ECP (>13.92 mL/mmHg, the highest quartile), after adjusting for age. Low ECP was associated with a 1.96-fold risk (95%CI: 1.38-2.78, p < 0.001) of HF after additional adjustment for conventional risk factors. After further adjustment for left ventricular hypertrophy, the results hardly changed (hazards ratio = 1.87, 95%CI: 1.31-2.66, p < 0.001). One SD increase in ECP (3.16 mL/mmHg) was associated with a decreased risk of HF by 28% (95%CI: 17%-37%). ECP provides a noninvasive and easily available measure from cardiopulmonary exercise tests in predicting HF. However, ECP did not provide additional value over maximal oxygen uptake.


Shared governance: is it a catalyst of change?
The purpose of this study is to evaluate a practical application of shared governance in a clinical health care setting. This investigation content analyzes monthly reports, personnel meeting minutes, individual preinterview and postinterview and satisfaction scores, a management assessment questionnaire, budget comparisons, and participant observations. Several identified shared governance applications include improved communication, conflict resolution, trust, team building, accountability, responsibility, quality care, and cost containment. This examination does support the value of the shared governance model as a catalyst of change. It indicates a need for more formalized committee structures, development of a peer review program and a staff action group to improve communications, and continued development of the shared governance model. However, this yearlong study strongly supports use of shared governance to increase job satisfaction, improve the budget, increase team building, and build job commitment.


Reduced Graphene Oxide-Reinforced Polymeric Films with Excellent Mechanical Robustness and Rapid and Highly Efficient Healing Properties.
The fabrication of nanofiller-reinforced intrinsic healable polymer composite films with both excellent mechanical robustness and highly efficient healability is challenging because the mobility of the polymer chains is suppressed by the incorporated nanofillers. In this study, we exploit the reversible host-guest interactions between nanofillers and the matrix polymer films and report the fabrication of intrinsically healable, reduced graphene oxide (RGO)-reinforced polymer composite films capable of conveniently and repeatedly healing cuts of several tens of micrometers wide. The healable films can be prepared via layer-by-layer assembly of poly(acrylic acid) (PAA) with complexes of branched poly(ethylenimine) grafted with ferrocene (bPEI-Fc) and RGO nanosheets modified with β-cyclodextrin (RGO-CD) (denoted as bPEI-Fc&RGO-CD). The as-prepared PAA/bPEI-Fc&RGO-CD films are mechanically robust with a Young's modulus of 17.2 ± 1.9 GPa and a hardness of 1.00 ± 0.30 GPa. The healing process involves two steps: (i) healing of cuts in an oxidation condition in which the host-guest interactions between bPEI-Fc and RGO-CD nanosheets are broken and the cuts on the films are healed; and (ii) reconstruction of host-guest interactions between bPEI-Fc and RGO-CD nanosheets via reduction to restore the original mechanical robustness of the films.


GLUT1 is highly expressed in cementoblasts but not in osteoblasts.
Cementum is a specialized mineralized tissue covering root surface of the tooth. Although the tissue's composition resembles bone, there are distinct structural and functional differences between the two mineralized tissues. In this study, the genes that are differentially expressed in putative cementoblasts (human cementum-derived cells [HCDCs]) compared with preosteoblastic cells (human bone marrow stromal cells [BMSCs]) were screened by two independent microarray systems, and some of the selected genes were further analyzed by quantitative real-time RT-PCR. The gene encoding glucose transporter 1 [GLUT1], which showed the greatest difference between the two groups by the latter analysis, was subjected to further analyses. High levels of the GLUT1 protein in HCDCs, but not in BMSCs, were detected by Western blotting and immunocytochemistry. Furthermore, intense immunoreactivities for GLUT1 were observed in cementoblasts and cementocytes but not in osteoblasts or osteocytes in human periodontal tissues. These results indicate that GLUT1 may play a role in cementogenesis and could serve as a biomarker to differentiate between cells of cementoblastic and osteoblastic lineage.


Predicting pleural invasion of invasive lung adenocarcinoma in the adjacent pleura by imaging histology.
The aim of the present study was to develop a non-invasive method based on histological imaging and clinical features for predicting the preoperative status of visceral pleural invasion (VPI) in patients with lung adenocarcinoma (LUAD) located near the pleura. VPI is associated with a worse prognosis of LUAD; therefore, early and accurate detection is critical for effective treatment planning. A total of 112 patients with preoperative computed tomography presentation of adjacent pleura and postoperative pathological findings confirmed as invasive LUAD were retrospectively enrolled. Clinical and histological imaging features were combined to develop a preoperative VPI prediction model and validate the model's efficacy. Finally, a nomogram for predicting LUAD was established and validated using a logistic regression algorithm. Both the clinical signature and radiomics signature (Rad signature) exhibited a perfect fit in the training cohort. The clinical signature was overfitted in the testing cohort, whereas the Rad signature showed a good fit. To combine clinical and radiomics signatures for optimal performance, a nomogram was created using the logistic regression algorithm. The results indicated that this approach had the highest predictive performance, with an area under the curve of 0.957 for the clinical signature and 0.900 for the Rad signature. In conclusion, histological imaging and clinical features can be combined in columnar maps to predict the preoperative VPI status of patients with adjacent pleural infiltrative lung carcinoma.


Contrasting internally and externally generated Atlantic Multidecadal Variability and the role for AMOC in CMIP6 historical simulations.
Atlantic multidecadal variability (AMV) has long been thought to be an expression of low-frequency variability in the Atlantic Meridional Overturning Circulation (AMOC). However, alternative hypotheses have been forwarded, including that AMV is primarily externally forced. Here, we review the current state of play by assessing historical simulations made for the sixth coupled model intercomparison project (CMIP6). Overall, the importance of external forcing is sensitive to the type of AMV index used, due to the importance of globally coherent externally forced signals in the models. There are also significant contrasts between the processes that drive internally and externally forced AMV, but these processes can be isolated by exploring the multivariate expression of AMV. Specifically, internal variability in CMIP6 models is consistent with an important role of ocean circulation and AMOC and the externally forced AMV is largely a surface-flux forced mechanism with little role for the ocean. Overall, the internal multivariate fingerprint of AMV is similar to the observed, but the externally forced fingerprint appears inconsistent with observations. Therefore, climate models still suggest a key role for ocean dynamics, and specifically AMOC, in observed AMV. Nevertheless, models remain deficient in a number of areas, and a stronger role for externally forced dynamical changes cannot be ruled out. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.


Membrane phospholipids alter nutrient transport and drug toxicity in tumorigenic fibroblasts.
The phospholipid polar head group composition of LM cell plasma membranes was nutritionally altered by choline analogue supplementation. Phosphatidylcholine (PC), normally 60% of total phospholipid, was depleted by 60 to 90% in membranes from cells cultured with N, N'-dimethylethanolamine (DME), N-monomethylethanolamine (ME), and ethanolamine (E). Enrichment of LM cell membranes with choline analogues, such as DME-, ME-, and E-containing phospholipids, decreased the transport of [3H]thymidine, [3H]2-deoxy-D-glucose, and [14C]3-O-methylglucose. Conversely, no change in the transport of [3H] uridine or [14C]aminoisobutyric acid was observed. The toxicity of antineoplastic drugs such as 5-fluorouracil, but not daunorubicin, doxorubicin, or methotrexate, was enhanced threefold in cells enriched with phospholipid containing choline or DME as compared to ME or E. Arrhenius plots of Na+-K+-ATPase activity demonstrated a characteristic temperature at 29 degrees C in plasma membranes from choline-fed cells, while those from analogue-fed cells showed an additional break at 20 degrees C and had higher energies of activation below this temperature. In addition, choline analogue supplementation altered the protein composition of the plasma membrane. The results reported herein demonstrate that nutritional alteration of LM fibroblast plasma membrane phospholipid polar head group composition affects several transport processes and toxicity of some anticancer drugs.


Interaction of prolactin and testosterone in the human prostate.
Three experiments were performed to determine whether human prolactin (hPr) affects prostatic uptake and metabolism of testosterone (T). 1) Patients with prostatic cancer were infused twice with radio-labelled androgens, the first time with basal hPR, the second time with oral thyrotrophin-releasing hormone (TRH)-elevated hPr. In 5/7, significant increases in metabolic clearance of dihydrotestosterone (DHT) and in conversion of T to DHT accompanied increased hPR. 2) The incorporation of labelled T into minced benign prostatic hypertrophy (BPH) tissue from subjects with high (40 ng/ml) hPR was measured and was found to be more than twice the uptake into tissue from those with low hPR (6.5 +/- 1.9 ng/ml). 3) Uptake and metabolism in vivo of a bolus of 3H-T by BPH and carcinomatous prostates was measured and was far greater in subjects whose hPR was elevated by chlorpromazine than in untreated controls. It is concluded that prolactin increases prostatic uptake and metabolism of T. It is suggested that the best management of prostatic cancer should include depletion of prolactin as well as androgen.


XBot2D: towards a robotics hybrid cloud architecture for field robotics.
Nowadays, robotics applications requiring the execution of complex tasks in real-world scenarios are still facing many challenges related to highly unstructured and dynamic environments in domains such as emergency response and search and rescue where robots have to operate for prolonged periods trading off computational performance with increased power autonomy and vice versa. In particular, there is a crucial need for robots capable of adapting to such settings while at the same time providing robustness and extended power autonomy. A possible approach to overcome the conflicting demand of a computational performing system with the need for long power autonomy is represented by cloud robotics, which can boost the computational capabilities of the robot while reducing the energy consumption by exploiting the offload of resources to the cloud. Nevertheless, the communication constraint due to limited bandwidth, latency, and connectivity, typical of field robotics, makes cloud-enabled robotics solutions challenging to deploy in real-world applications. In this context, we designed and realized the XBot2D software architecture, which provides a hybrid cloud manager capable of dynamically and seamlessly allocating robotics skills to perform a distributed computation based on the current network condition and the required latency, and computational/energy resources of the robot in use. The proposed framework leverage on the two dimensions, i.e., 2D (local and cloud), in a transparent way for the user, providing support for Real-Time (RT) skills execution on the local robot, as well as machine learning and A.I. resources on the cloud with the possibility to automatically relocate the above based on the required performances and communication quality. XBot2D implementation and its functionalities are presented and validated in realistic tasks involving the CENTAURO robot and the Amazon Web Service Elastic Computing Cloud (AWS EC2) infrastructure with different network conditions.


13C-NMR study of 4-azasteroids in solution and solid state.
A group of biologically active 4-azasteroids was studied by 13C-NMR spectroscopy in solution and in the solid phase. A full assignment of signals in the spectra of samples in chloroform was performed for thirteen 4-azasteroids using two-dimensional techniques. Substituent and steric effects of a nitrogen atom, and their influence on chemical shifts of the neighboring carbon atoms are discussed. CP MAS spectra were obtained for five 4-azasteroids including finasteride. The spectra confirmed polymorphism of the latter compound. In addition to the polymorphic forms that are already known, a new molecular complex of finasteride with dioxane is reported.


The mannose 6-phosphate/insulin-like growth factor 2 receptor mediates plasminogen-induced efferocytosis.
The plasminogen system is harnessed in a wide variety of physiological processes, such as fibrinolysis, cell migration, or efferocytosis; and accordingly, it is essential upon inflammation, tissue remodeling, wound healing, and for homeostatic maintenance in general. Previously, we identified a plasminogen receptor in the mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R, CD222). Here, we demonstrate by means of genetic knockdown, knockout, and rescue approaches combined with functional studies that M6P/IGF2R is up-regulated on the surface of macrophages, recognizes plasminogen exposed on the surface of apoptotic cells, and mediates plasminogen-induced efferocytosis. The level of uptake of plasminogen-coated apoptotic cells inversely correlates with the TNF-α production by phagocytes indicating tissue clearance without inflammation by this mechanism. Our results reveal an up-to-now undetermined function of M6P/IGF2R in clearance of apoptotic cells, which is crucial for tissue homeostasis.


A phase II trial of intraperitoneal cisplatin and etoposide as consolidation therapy in patients with Stage II-IV epithelial ovarian cancer following negative surgical assessment.
To determine the efficacy of three courses of intraperitoneal (i.p.) cisplatin (CDDP) and etoposide (VP-16) as consolidation therapy following pathologically negative second-look surgical reassessment for Stage IIC-IV epithelial ovarian cancer (EOC). Between September 1988 and April 1996, 40 patients were treated with three cycles of i.p. CDDP (100 mg/m2)/VP-16 (200 mg/m2) as consolidation therapy. Survival was compared to that of a group of 46 contemporaneous patients undergoing observation only. Median age of the 36 eligible patients was 52 years (range 30-70 years). Stage distribution was II (3), III (31), and IV (2); histologic grade was 1 (2), 2 (7), 3 (25), and not recorded (2); and residual disease at completion of initial surgery was none/microscopic in 13/36 (36%) patients. Median age of the 46 patients who did not receive consolidation was 52 years (range, 27-80 years); stage distribution was II (18), III (26), and IV (2); histologic grade was 1 (5), 2 (12), 3 (28), and not recorded (1). With a median follow-up of 36 months in both groups, 14/36 (39%) of the protocol group have recurred compared with 25/46 (54%) of those undergoing observation alone. Median disease-free survival (DFS) for the observed patients is 28.5 months and has not been reached in the consolidation group. Disease-free survival distribution between the two groups was compared using the log-rank test and was found to be significant (P = 0.03). Multivariate analysis revealed that the only significant predictor of improved DFS was protocol treatment (P < 0.01). Intraperitoneal consolidation with CDDP/VP-16 following negative second-look reassessment in patients with advanced EOC resulted in a significant increase in DFS compared to nonprotocol patients treated concurrently who underwent observation alone.


Listeria monocytogenes from food and food industry environments with reduced susceptibility to benzalkonium chloride, sodium hypochlorite, and peracetic acid.
The growing number of Listeria monocytogenes strains displaying increased tolerance to sanitizers widely applied in the food industry is becoming a problem. The aims of this study were to evaluate the susceptibility of L. monocytogenes isolates from food and food industry environments to sanitizers (benzalkonium chloride, sodium hypochlorite, peracetic acid, and chlorhexidine) and heavy metals (cadmium chloride), as well as to investigate the presence of the main genes related to efflux pumps. All 82 isolates showed reduced susceptibility to benzalkonium chloride (MIC from 16 to 128 µg mL-1), sodium hypochlorite (MIC of ≥ 2048 µg mL-1), and peracetic acid (MIC from 512 to ≥ 2048 µg mL-1), while 22 isolates showed reduced susceptibility to cadmium chloride (MIC > 70 µg mL-1). Susceptibility to chlorhexidine was found (MIC from 2 to 16 µg mL-1). PCR-based analysis revealed that mdrl and lde genes were harbored by 14.6% (12/82) and 40.2% (33/82) of the isolates, respectively. This study demonstrates the presence of L. monocytogenes from food and food industry environments with reduced susceptibility to sanitizers commonly used in food processing environments, highlighting the importance of continuous monitoring of the tolerance profile of this microorganism to sanitizers, as well as the need for strict control of sanitation conditions in food industries.


Positive identification in a case of intentional extreme fragmentation.
The investigation of the first of the murders of young males to which Jeffrey Dahmer confessed led to systematic survey of two acres of semirural property in Bath Township, Ohio. The survey revealed the fragmentary skeleton of a young adult male, as well as bones of several species of animals. Through archaeobiological analysis, the animal bones were identified and taphonomic modifications documented. The human bones were dry and weathered, and many were rodent-gnawed, indicating that they had been exposed for many years. The human bones displayed an extreme degree of splintering, warping, bending, and spiral breakage. The only relatively complete bone was a cervical vertebra. Dismemberment and breakage had been accomplished by cutting, blunt force, and, in the case of the ribs, manual bending. Even in so extreme a case of intentional fragmentation, however, forensic anthropological analysis resulted in positive identification, with the primary criteria based on matching osteological features evident in premortem and postmortem radiographs of a cervical vertebra.


Severe folate deficiency impairs natural killer cell-mediated cytotoxicity in rats.
Dietary folate deficiency enhances, whereas folate supplementation suppresses, the development of several cancers. This study investigated the effect of folate deficiency on natural killer cell (NK)-mediated cytotoxicity, which is important in immune surveillance against tumor cells. In Experiment 1, severe folate deficiency was induced in rats by feeding an amino acid-defined diet containing 0 mg folate and 10 g succinylsulfathiazole/kg diet. Control and folate-supplemented rats were fed the same diet containing 2 (basal requirement) and 8 mg folate/kg diet, respectively. Severe folate deficiency at the end of wk 5 was associated with 20% growth retardation, a 60% reduction in lymphocyte counts and significantly impaired NK-mediated cytotoxicity compared with the control and folate-supplemented groups (P < 0.02). The lesser degree of severe folate deficiency achieved by wk 4 was not associated with impaired NK-mediated cytotoxicity. Folate supplementation at 4x the basal requirement did not significantly enhance NK-mediated cytotoxicity at either time point. In Experiment 2, moderate folate deficiency was induced in rats by feeding the same diet without succinylsulfathiazole. NK-mediated cytotoxicity in the moderately folate-deficient rats (without growth retardation or lymphopenia) was not significantly different from that in controls. Although severe folate deficiency may have adverse effects on NK-mediated cytotoxicity, moderate folate deficiency, a degree of depletion associated with an increased risk of several cancers, appears not to affect NK-mediated cytotoxicity in rats. Furthermore, a modest level of folate supplementation above the basal requirement does not enhance NK-mediated cytotoxicity. These data collectively suggest that NK-mediated cytotoxicity is not a likely mechanism by which folate status modulates carcinogenesis.


Effective interaction between a colloid and a soft interface near criticality.
Within mean-field theory we determine the universal scaling function for the effective force acting on a single colloid located near the interface between two coexisting liquid phases of a binary liquid mixture close to its critical consolute point. This is the first study of critical Casimir forces emerging from the confinement of a fluctuating medium by at least one shape responsive, soft interface, instead of by rigid walls only as studied previously. For this specific system, our semi-analytical calculation illustrates that knowledge of the colloid-induced, deformed shape of the interface allows one to accurately describe the effective interaction potential between the colloid and the interface. Moreover, our analysis demonstrates that the critical Casimir force involving a deformable interface is accurately described by a universal scaling function, the shape of which differs from that one for rigid walls.


[Arthroscope monitored solution of adult intramuscular injection associated gluteal muscle contracture by radiofrequency].
To evaluate the result of releasing adult intramuscular injection associated gluteal muscle contracture under the monitor of arthroscope by radiofrequency probe. From June 2001 to June 2005, 108 cases of bilateral gluteal muscle contracture were treated with radiofrequency colation under the arthroscope and solution with an average age of 24 years (from 18 to 40 years). There were 57 males and 51 females. Preoperatively, the course of the outline of the femur greater trochanter the sciatic nerve in buttocks and the area of gluteal muscle contracture were marked. With the patients firmly anchored in the straight lateral position, normal saline (which contains Adnephrin) was injected between the surface of contracted gluteus and subcutaneous fat to reduce bleeding in operation. The ports for the motorized shaver and radiofrequency probe were located at the edge of gluteal muscle contracture and were 5 mm superior to the greater trochanter. The 6 mm diameter port for the arthroscope was 3 cm inferior to the greater trochanter. Space was made between contracture bands and overlying subcutaneous tissue with a periosteal elevator by blunt dissection. After the anterior and posterior edge of the contracture bands were fully revealed, normal saline were filled in the space. With the monitor of arthroscope, the procedures were: removing fatty tissue from the surface of the contracture bands with motorized shaver, then cutting off the contracture bands curve and carefully probing and cutting off contracture bands which were mixed in gluteus maximus with radiofrequency probe, finally hemostasis by radiofrequency probe. In the operation flexion, adduction, internal rotation and straightening hip joint were repeated, until it got normal range of motion without snap and bleeding. Results One hundred and one patients were followed up with an average of 19 months. According to a comprehensive evaluating system, 91 cases were excellent, 7 were good, and 3 were fair. No infection, recurrence and neurovascular injury occurred. Gluteal muscle contracture could be effectively released with radiofrequency vaporization and solution. The technique has the advantage of easy to manipulate, minimally invasive, painless, safety and reliable curative effect, and is good for early functional exercises.


A Low-Cost Time-Correlated Single Photon Counting Portable DNA Analyzer.
Photon-counting analysis of nucleic acids plays a key role in many diagnostics applications for its accurate and non-invasive nature. However, conventional photon-counting instrumentations are bulky and expensive due to the use of conventional optics and a lack of optimization of electronics. In this paper, we present a portable, low-cost time-correlated single photon-counting (TCSPC) analysis system for DNA detection. Both optical and electronic subsystems are carefully designed to provide effective emission filtering and size reduction, delivering good DNA detection and fluorescence lifetime extraction performance. DNA detection has been verified by fluorescence lifetime measurements of a V-carbazole conjugated fluorophore lifetime bioassay. The time-to-digital module of the proposed TCSPC system achieves a full width at half maximum (FWHM) timing resolution from 121 to 145 ps and a differential non-linearity (DNL) between -8.5% and +9.7% of the least significant bit (LSB) within the 500 ns full-scale range (FSR). With a detection limit of 6.25 nM and a dynamic range of 6.8 ns, the proposed TCSPC system demonstrates the enabling technology for rapid, point-of-care DNA diagnostics.


[Giant prostatic calculus with neurogenic bladder disease and prostate diverticulum: a case report and review of the literature].
To study the etiology, clinical manifestation, diagnosis and treatment of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum. We retrospectively analyzed the clinical data of a case of giant prostatic calculus with neurogenic bladder disease and prostate diverticulum and reviewed the relevant literature. The patient was a 37-year-old man, with urinary incontinence for 22 years and intermittent dysuria with frequent micturition for 9 years, aggravated in the past 3 months. He had received surgery for spina bifida and giant vesico-prostatic calculus. The results of preoperative routine urinary examination were as follows: WBC 17 -20/HPF, RBC 12 - 15/HPF. KUB, IVU and pelvic CT revealed spina bifida occulta, neurogenic bladder and giant prostatic calculus. The patient underwent TURP and transurethral lithotripsy with holmium-YAG laser. The prostatic calculus was carbonate apatite in composition. Urinary dynamic images at 2 weeks after surgery exhibited significant improvement in the highest urine flow rate and residual urine volume. Seventeen months of postoperative follow-up showed dramatically improved urinary incontinence and thicker urine stream. Prostate diverticulum with prostatic giant calculus is very rare, and neurogenic bladder may play a role in its etiology. Cystoscopy is an accurate screening method for its diagnosis. For the young patients and those who wish to retain sexual function, TURP combined with holmium laser lithotripsy can be employed, and intraoperative rectal examination should be taken to ensure complete removal of calculi.


Phosphorylation of Shc proteins in human sperm in response to capacitation and progesterone treatment.
Several authors have demonstrated the involvement of tyrosine kinases during sperm capacitation and acrosome reaction. Shc proteins (p46Shc, p52Shc, and p66Shc) are cytoplasmic substrates of activated tyrosine kinases and are widely expressed in mammalian somatic tissues. Experiments were designed to demonstrate the presence of Shc in spermatozoa and to study its involvement in the signal transduction events leading to acrosome reaction. Anti-Shc antibodies strongly reacted with the acrosomal region of methanol-fixed human sperm. Only one Shc isoform (p52Shc) was detected on Western blot. To study the degree of phosphorylation of Shc during capacitation and acrosome reaction, sperm samples were divided into two groups: noncapacitated and capacitated/progesterone treated. Lysates from both groups were immunoprecipitated with anti-phosphotyrosine antibodies and the precipitated (i.e., phosphorylated) proteins were tested with anti-Shc antibodies. The intensity of p52Shc was clearly increased in capacitated/progesterone-stimulated cells.


The corrosion behaviour of Ti-6Al-4V, Ti-6Al-7Nb and Ti-13Nb-13Zr in protein solutions.
Ti alloys are used in orthopaedic applications owing to their appropriate mechanical properties and their excellent corrosion resistance. The release of titanium and the other alloying elements into the surrounding tissue has been reported due either to passive corrosion or accelerating processes such as wear. Since the passive layer can be broken down in certain circumstances by wear it is important to study the ability of these alloys to repassivate in biological environments, in particular in the presence of proteins, and evaluate how the repassivated surface may vary from the original surface. In this study we investigated the ability of Ti-6Al-4V, Ti-6Al-7Nb and Ti-13Nb-13Zr to repassivate in phosphate buffered saline (PBS), bovine albumin solutions in PBS and 10% foetal calf serum in PBS at different pH values and at different albumin concentrations. It was found that an increase in pH had a greater effect on the corrosion behaviour of Ti-6Al-4V and Ti-6Al-7Nb than on Ti-13Nb-13Zr in PBS and that the addition of protein to the PBS reduced the influence of pH on the corrosion behaviour of all the alloys. The effect of the corrosion and repassivation was investigated by measuring changes in the surface hardness of the alloys and it was found that corrosion reduced the hardness of the surface oxides of all the alloys. In PBS the reduction was smallest for Ti-6Al-4V and largest for Ti-13Nb- 3Zr and that corrosion in protein solutions further reduced the hardness of the surface oxides. This effect was greater for Ti-6Al-4V and Ti-6Al-7Nb than for Ti-13Nb-13Zr. In conclusion, proteins in the environment appear to interact with the repassivation process at the surface of these alloys and influence the resulting surface properties.


Recommended modification of dilution procedure used for bacteriological examination of shellfish.
The dilution procedure recommended by the American Public Health Association for use in bacteriological analysis of shellfish samples may cause an underestimation of the number of bacteria in shellfish. Modifications of that procedure to include preparation of the first dilution of the shellfish homogenate on a weight rather than a volume basis, and the inoculation of 1 g portions of the shellfish from a dilution of the homogenate, have been shown to significantly increase the recovery of fecal coliform bacteria from oyster samples. It is recommended that these modifications be adopted by the American Public Health Association.