Job demands, job resources, and behavior in times of sickness: An analysis across German nursing homes.
The concept of presenteeism, that is, employees coming to work despite being sick, has recently received more attention in the literature. Presenteeism not only threatens employees' health but also substantially drains productivity and drives considerable costs. When they are sick, employees have the choice of whether to go to work or to stay at home. Therefore, determinants of (sickness) absenteeism and presenteeism should be examined simultaneously. Nursing homes are faced with a particularly high prevalence of both absenteeism and presenteeism and are therefore a relevant object of investigation. The aim of our study is to analyze the effect of job demands and job resources on absenteeism, presenteeism, and the tendency to choose one behavior (being absent or being present in times of sickness) rather than the other over the last 12 months. To do so, we identify the determinants of absenteeism and/or presenteeism behavior based on theory and existing research about absenteeism, presenteeism, and job demands and job resources. After our empirical analysis, we provide explanations for our findings and offer practical suggestions for how to decrease the frequencies of absenteeism and presenteeism. In this study, a sample of 212 nurses from German nursing homes was used for an ordinal logistic regression analysis. Our results show that role overload significantly increases the frequencies of both absenteeism and presenteeism. A good team climate decreases absenteeism and increases the tendency to choose presenteeism rather than absenteeism, whereas strategic training and development opportunities decrease presenteeism and increase the tendency to choose absenteeism rather than presenteeism.


Personal health care of internal medicine residents.
Medical residents, as part of their job to balance the demands of their work with caring for themselves so as to be mentally, emotionally, and physically sound to stay clinically competent. While regulatory and legislative attempts at limiting medical resident work hours have materialized but have yet to attain passage, there are fairly little data looking into how residents cope up with their demands and yet attend to their own personal health. Anonymous mailed survey. Three hundred and thirty-seven residents from all internal medicine residency programs within United States. We conducted a survey in the form of a questionnaire that was sent by e-mail to the program directors of various internal medicine residency programs within the United States, and responses were collected between May 19 and June 21, 2009. Response was well appreciated with total number of participants of 337 with even demographical distribution in gender, residency year, AMG/IMG, age group. Seventy-one percent of the residents felt that they would prefer getting admitted to their own hospital for any acute medical or surgical condition. Of the 216 residents who have had received health care in the past, almost half of them chose their own hospital because of the proximity, while 45% did not choose their own hospital despite proximity. Two out of three residents missed their doctors appointments or cancelled them due to demands of medical training. Only half of the residents have a primary care physician and almost 80% of them did not have their yearly health checkup. Close to 30% held back information regarding their social and sexual history from their provider because of privacy and confidentiality concerns. Eighty percent of residents never received information about barriers that physicians may face in obtaining care for their socially embarrassing conditions. Seventy percent felt that their performance then was suboptimal because of that health condition and also felt sick but did not drop the call. Half of the residents had concerns that they might be having a psychiatric illness, but only 5% of them received a formal evaluation at their own hospital and 23 (12.4%) at an outside hospital. It is very important to have more studies to emphasize on resident's physical and mental health and encourage them to have a primary care physician. There are several reasons preventing residents from getting a formal evaluation, confidentiality reasons, lack of time - schedule constraints, fear of being labeled, and social repercussions are few of them. Program directors should encourage the residents to not only care of the health of their patients but also be enthusiastic about their personal health issues for upgraded, revised patient care, and ultimately for their overall well-being.


Successful delivery after conservative resectoscopic surgery in a patient with a uterine tumor resembling ovarian sex cord tumor with myometrial invasion.
Uterine tumor resembling ovarian sex cord tumors (UTROSCT) is an extremely rare type of uterine stromal neoplasm that exhibits prominent sex cord-like differentiation. The clinical characteristics of a UTROSCT are not fully understood. Most reported cases of UTROSCT were treated by hysterectomy with or without bilateral salpingo-oophorectomy; however, a few cases have been treated by only tumor resection in patients who had a strong desire to preserve their fertility. We present a case of UTROSCT with myometrial invasion, which resulted in a successful delivery after the patient was treated by resectoscopic surgery and conservation of the uterus, and a brief review of the literature.


A novel technique for improved lesions in the coronary sinus. comparison of bipolar and unipolar ablation.
The stepwise approach to radiofrequency (RF) ablation of atrial fibrillation (AF) can include ablation of the coronary sinus (CS) by RF delivery at the left atrium (LA) and/or within the CS. In both cases, the energy is applied between the tip electrode of a percutaneous catheter and a dispersive electrode on the body surface. We explored the feasibility of using the electrode rings of a diagnostic catheter placed in the CS as dispersive electrode(s) for RF delivery within the LA and compared this technique to an established CS ablation method.Excised pig hearts were superfused with a pulsatile saline flow. Bipolar ablation was performed between a saline-irrigated (20 mL/minute) 4-mm tip electrode placed in the LA adjacent to the CS and 7 electrode rings of a 6F, septapolar, 4-mm nonirrigated electrode placed within the CS adjacent to the LA endocardial electrode. Unipolar ablation was performed between the endocardial electrode and dispersive electrode. A continuous transmural lesion was produced in 6/8 (75%) attempts with bipolar ablation, but in 0/6 (0%) attempts with unipolar ablation. However, the incidence of steam pop tended to be increased with bipolar ablation.Bipolar ablation of the CS appears to be highly effective for creating a transmural LA-CS lesion.


Case Report: A de novo NLRP3 variant resulting in autoinflammatory disease in a Chinese newborn.
Cryopyrin-associated periodic syndromes (CAPS) have been considered autoinflammatory diseases resulting from NLRP3 gene mutations. In recent years, these conditions have been redefined as NLRP3-associated autoinflammatory diseases (NLRP3-AID). Our previous study highlighted a case of a Chinese individual carrying the de novo NLRP3 mutation. A female child carrying a de novo variant (c.1718T>G, p. L573W) in the NLRP3 gene was presented in this work. The patient manifested various symptoms, including recurrent fever, a rash resembling urticaria, arthritis, physical growth retardation, a notable prominence of the forehead, and a flat nose bridge. Additionally, inflammatory markers, like WBC count, PLT count, CRP, ESR, and IL-6 showed elevated levels. Additionally, we observed interstitial pulmonary disease in the patient, which is not frequently mentioned in previous studies. Notably, the proband did not present with any ocular, auditory, or neurological symptoms. After 12 weeks of subcutaneous canakinumab injection, there was a clear improvement in the patient's clinical manifestations and inflammatory markers. Our study contributes to broadening the clinical spectrum of established pathogenic variants of NLRP3 gene, which are related to NLRP3-AID.


[The sprotte needle decreases the incidence of postspinal headache].
Postspinal headache (PSH) is the most frequent complication of spinal anesthesia. The factors responsible for the development of PSH include needle size, shape of the needle tip, patient's age, sex, infusion volume and period of resting. The purpose of this study is to compare the incidence of PSH between two different types of needle, Sprotte needle and Quincke needle. The Sprotte needle is characterized by a round profiled tip equipped with a lateral orifice. Our investigation by questionnaires revealed that the incidences of PSH after using either 22G Sprotte needle or 21-25G Quincke needle were 0% and 38.8%, respectively. We conclude that the Sprotte needle decrease the incidence of PSH.


[Causes of local edema in the infiltrative edematous form of breast cancer].
The study was concerned with comparison of the characteristics of primary tumor in 80 cases of the infiltrative-edematous form of breast cancer. The control group included 192 patients with breast cancer unaggravated by edema. The involvement of regional lymph nodes proved to be the same in both groups. On the average tumors in the edematous breast cancer group were much larger and the rate of their growth much higher than in controls. The said pathogenetic differences are discussed. It is suggested that edema is primarily caused by disturbances in transcapillary metabolism at tumor site which are, in turn, induced by tumor metabolites.


The necessity of social medicine in medical education.
Research and clinical experience reliably and repeatedly demonstrate that the determinants of health are most accurately conceptualized as biosocial phenomena, in which health and disease emerge through the interaction between biology and the social environment. Increased appreciation of biosocial approaches have already driven change in premedical education and focused attention on population health in current U.S. health care reform. Medical education, however, places primary emphasis on biomedicine and often fails to emphasize and educate students and trainees about the social forces that shape disease and illness patterns. The authors of this Commentary argue that medical education requires a comprehensive transformation to incorporate rigorous biosocial training to ensure that all future health professionals are equipped with the knowledge and skills necessary to practice social medicine. Three distinct models for accomplishing such transformation are presented: SocMed's monthlong, elective courses in Northern Uganda and Haiti; Harvard Medical School's semester-long, required social medicine course; and the Lebanese American University's curricular integration of social medicine throughout its entire four-year curriculum. Successful implementation of social medicine training requires the institutionalization of biosocial curricula; the utilization of innovative, engaging pedagogies; and the involvement of health professions students from broad demographic backgrounds and with all career interests. The achievement of such transformational and necessary change to medical education will prepare future health practitioners working in all settings to respond more proactively and comprehensively to the health needs of all populations.


Femoral catheters and deep venous thrombosis: a prospective evaluation with venous duplex sonography.
Femoral vein cannulation (FVC) with 8.5F Swan-Ganz catheter introducers allows expeditious intravenous access and rapid volume infusion; however, the incidence of associated iliofemoral deep venous thrombosis (DVT) is unknown. Trauma patients (n = 76) requiring unilateral FVC were prospectively entered into a study where they were resuscitated via FVC and serially evaluated with bilateral venous duplex sonography (VDS). The incidence of DVT in catheterized femoral veins was compared with that in uncatheterized femoral veins. Catheters were removed promptly and VDS was performed within 24 hours and weekly for 1 month. Iliofemoral DVTs were identified in 11 of the 76 patients (14%). Iliofemoral DVTs occurred on the cannulated side in 9 (81.8%) compared with 2 (18.2%) on the uncannulated side (p < 0.05). We conclude that the use of the 8.5F FVC is associated with an increased incidence of DVT and that despite its convenience, this technique should not be routine.


Regulated expression of G protein-coupled receptor kinases (GRK's) and beta-arrestins in osteoblasts.
Desensitization of G-protein coupled receptors (GPCR's) is largely mediated by a family of enzymes and protein co-factors termed GRKs and arrestins, respectively. In the present studies, we investigated expression of GRKs and arrestins in osteoblastic cell lines concentrating on the enzymes (GRK2 and GRK3) and protein co-factors (beta-arrestint 1 and beta-arrestin 2) that play dominant roles in regulating GPCR responsiveness in most tissues and cell types. We found that osteoblastic cells express similar amounts of GRK2 with either undetectable or lesser amounts of GRK3. In contrast, expression of beta-arrestin 1 and beta-arrestin 2 by osteoblastic cells varied between cell lines. To determine if GRK2 or beta-arrestin expression is modulated during osteoblast development, we assessed expression of GRK2 and beta-arrestin proteins during differentiation of the mouse osteoblastic cell line MC3T3-E1 cells over a 21-day period. We found that expression of GRK2 and beta-arrestin 2 increased to maximal levels by day 7 and then decreased 4-fold by day 21. In contrast, expression of beta-arrestin 1 increased to maximal levels by day 14 and then decreased 2-fold by day 21. Over this same time period (days 7-21), PTH/PTHrP receptor number decreased to a greater extent than the decrease in PTH(1-34)-induced cAMP generation, suggesting that responsiveness of individual PTH/PTHrP receptors was enhanced in differentiated cells. We conclude that (1) osteoblastic cell lines differentially express the enzymes and protein co-factors that modulate GPCR responsiveness and (2) expression of both GRK2 and beta-arrestins is temporally regulated during osteoblast development. These data are consistent with the notion that GPCR responsiveness may be differentially regulated in osteoblastic cell lines and during osteoblast development.


Patients age and results of treatment in discogenic cauda equina syndrome.
Cauda equina syndrome is a feared complication of lumbar disc disease. Despite of early surgery it frequently leaves persistent effects. Localisation, type, and duration of spinal nerve roots compression are quoted as the most important factors influencing the results of treatment. Statistical evaluation of data acquired by examinations of 58 persons operated on for this disease et the Department of Neurosurgery in Kosice within the period from January 1st, 1982 to December 31st, 1991 has shown that the further important facts are ageing of tissues and impairment of microcirculation. In patients over the age of 45 the recovery of motor and sexual functions, as well as the voluntary control of rectal sphincters, and the working ability were significantly worse. It is suggested thereby that in elderly persons with a proven intervertebral disc disease an early surgical intervention is indicated. (Tab. 7, Ref. 23.)


Surgical treatment of the pancreatic stump: preventive strategies of pancreatic fistula after pancreatoduodenectomy for cancer.
The institutions with high volume of pancreatic surgery report morbidity rate from 30% to 50% and mortality less than 5% after pancreaticoduodenectomy (PD). At the present, the most significant cause of morbidity and mortality is pancreatic fistula (PF). The purpose of the study is to identify the most important clinical factors which may predict PF development and eventually suggest alternative approaches to the pancreatic stump management. A retrospective analysis of a clinical data base of a tertiary care Hospital was performed. From 2002 to 2012 a single Surgeon prospectively performed 150 pancreaticoduodenectomies for cancer. Four different techniques were used: end to end pancreaticojejunostomy, end to side pancreaticojejunostomy, pancreatic duct occlusion and duct to mucosa anastomosis. The intraoperative gland texture was classified as soft, firm and hard. The duct size was preoperatively (CT scan) and intraoperatively recorded and classified: < 3 mm small, 3-6 mm medium, > 6 mm large. The histopathological characteristic of the gland fibrosis was graduate as low 1, moderate 2, high 3. Relationships between pre and intraoperative duct size measurement, pancreatic texture and pancreatic fibrosis grading were highly significant. Small duct and soft pancreas with low grade fibrosis are the most important risk factors for pancreatic fistula development. The proper selection of pancreatic stump management or the decision to refer the high risk patients to high volume Center can be suggested by the elevated correspondence of pre and intraoperative duct diameter with the related pancreatic fibrosis grade and gland consistency. Preoperative assessment of the pancreatic duct makes possible to predict the risk of pancreatic fistula.


Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats.
Crocin and safranal are the active substances of saffron and have many biological properties. In the present study, we compared the effects of crocin, safranal and diclofenac on local inflammation and its induced pain in rats. Local inflammation was induced by intraplantar (ipl) injection of carrageenan (100 μl, 2%). Paw thickness was measured before and after carrageenan injection. Inflammatory pain responses including cold allodynia, mechanical allodynia and hyperalgesia were assessed using acetone spray and von Frey filament tests, respectively. The number of neutrophils in inflammatory zone was counted 6.5 h after injection of carrageenan. Carrageenan produced edema, cold allodynia, mechanical allodynia and hyperalgesia and caused neutrophil infiltration in paw tissues. Crocin at doses of 25, 50 and 100 mg/kg, safranal at doses of 0.5, 1 and 2 mg/kg and diclofenac (as a reference drug) at a dose of 10 mg/kg attenuated edema, suppressed inflammatory pain responses and decreased the number of neutrophils. The present study showed anti-inflammatory and antinociceptive activities for crocin, safranal and diclofenac in carrageenan model of local inflammation and inflammatory pain.


Signal processing, glycosylation, and secretion of mutant hemagglutinins of a human influenza virus by Saccharomyces cerevisiae.
We investigated the nature of signal recognition, transport, and secretion of mutant hemagglutinins (HAs) of a human influenza virus by the yeast Saccharomyces cerevisiae. The cDNA sequences encoding variant forms of influenza HA were expressed in S. cerevisiae. The HA polypeptides (HA500 and HA325) that were synthesized with their N-terminal signal peptides were correctly targeted to the membrane compartment where they were glycosylated. In contrast, the HA polypeptides (HA484 and HA308) lacking the signal peptide were expressed in the cytoplasm and did not undergo any glycosidic modification, demonstrating the importance of the heterologous signal sequence in the early steps of translocation in S. cerevisiae. The analysis of the N-terminal amino acid sequence of HA500 and HA325 polypeptides demonstrated the correct cleavage of the signal peptide, indicating the structural compatibility of a heterologous signal peptide for efficient recognition and processing by the yeast translocation machinery. The membrane-sequestered and glycosylated HA polypeptides were relatively stable in S. cerevisiae compared with the signal-minus, nonglycosylated HA molecules. Although both the anchor-minus HA (HA500) and HA1 (HA325) polypeptides were targeted efficiently to the membrane, their glycosylation and transport patterns were shown to be different. During pulse-chase, the HA500 remained cell-associated with no detectable secretion into the extracellular medium, whereas the HA325 secreted into the medium. Furthermore, only the cell-associated and secreted forms of HA325 and not HA500 appeared to have undergone hyperglycosylation with the extensive addition of high-molecular-weight outer-chain mannans. Possible reasons for the observed phenotypic behavior of these two mutant HAs are discussed.


The flexibility and topology of simian virus 40 DNA in minichromosomes.
The linking number of DNA in minichromosomes increases by 2 turns during SV40 assembly. Changes in temperature also influence the average linking number of the total intracellular forms of SV40 DNA. When the isolated minichromosomes assembled in vivo are incubated with topoisomerase I at 33 degrees C in vitro, the linking number of SV40 DNA decreases. This decrease is about: -1.1 turns for minichromosomes with an average nucleosome spacing of 198 base pairs (bp), wt776; and -0.6 turns for minichromosomes containing a shorter average nucleosome repeat (177 bp), tsC219. The difference between the average linking number of naked SV40 DNA relaxed with topoI at 33 degrees C and minichromosomes relaxed with the enzyme at the same temperature indicates that SV40 chromatin contains on the average 26 nucleosomes. However, the results of studies obtained both on DNA flexibility in chromatin and in naked DNA, and on the shape of the topoisomer distribution curves, indicate that all of the minichromosomes, regardless of their overall structure, do not contain the same number of nucleosomes; this heterogeneity may be as large as 8 nucleosomes. We find no apparent correlation between the amount of minichromosomes containing unconstrained torsional stress and the abundance of the molecules with a structure characteristic of transcriptionally active chromatin.


Synthesis of Hierarchical Porous SAPO-34 and Its Catalytic Activity for 4,6-Dimethyldibenzothiophene.
Zeolite SAPO-34 has been widely used in the industry because of its special pore structure and wide distribution of acid sites in the pore channel. However, traditional SAPO-34 with a small pore size suffers from carbon deposition and deactivation in catalytic reactions, and its inability to catalytically convert bulky organic molecules limits its industrial application. Meanwhile, impurities of SAPO-5, which have weak acidity leading to rapid catalyst deactivation, appear in SAPO-34 zeolite. Therefore, it is of great significance to synthesize SAPO-34 zeolite with a mesoporous pore structure, which can significantly improve the transfer of molecules in zeolites. In this paper, SAPO-34 zeolite with a hierarchical pore structure was synthesized, and its hydrodesulfurization performance for 4,6-dimethyldibenzothiophene (4,6-DMDBT) was studied in a fixed bed reactor. The characteristic results show that BET-specific surface area, micropore volume, and mesoporous volume of synthesized SAPO-34 are 754 m2 g-1, 0.25, and 0.23 cm3 g-1 respectively, and the pore size is mainly concentrated at 4 nm. The catalytic conversion of 4,6-DMDMT with Co- and Mo-supported SAPO-34 is about 83%, which is much higher than the catalytic performance of Al2O3.


[Glucocorticoid therapy for children with idiopathic nephrotic syndrome].
The glucocorticoid treatment of patients with idiopathic nephrotic syndrome in children was reported especially focused upon the dose of initial treatment and different effect of various glucocorticoids if they were used equivalently. It appeared that lower dose prednisolone; 40 mg/m2 bsa (body surface area) was also effective same as 60 mg/m2 bsa of protocol of ISKDC (International Study of Kidney Disease in Children) for the initial treatment if time for free proteinuria was taken as index. Therefore, it was considered favorable that we could use lower dose to avoid various adverse effects of glucocorticoids. Clinically it was felt that some different effects were present despite of their equivalent use. The equivalency of various glucocorticoids was based upon anti-inflammatory effect experimentally. The etiology of idiopathic nephrotic syndrome has not been well known, however some sort of immune disorder has been thought most important. Therefore, it might be acceptable if effect of glucocorticoid treatment of nephrotic syndrome is evaluated on the basis of immunosuppression. It is hoped that these empirically proven evidence should be analysed fundamentally in the near future.


A subset of Actinobacillus pleuropneumoniae in vivo induced promoters respond to branched-chain amino acid limitation.
Actinobacillus pleuropneumoniae is the causative agent of a necrotizing hemorrhagic pleuropneumonia in swine. In this study, we investigate the possibility that the limitation of branched-chain amino acids is a stimulus that A. pleuropneumoniae will encounter during infection and will respond to by up-regulation of genes involved in branched-chain amino acid biosynthesis and virulence. Actinobacillus pleuropneumoniae genetic loci that are specifically induced during infection were screened in vitro for expression in response to limitation of branched-chain amino acids. Of 32 in vivo induced promoter clones screened in vitro, eight were induced on chemically defined medium without isoleucine, leucine and valine as compared to complete chemically defined medium. We identify the genomic context of each clone and discuss its relevance to branched-chain amino acid limitation and virulence. We conclude that limitation of branched-chain amino acids is a cue for expression of a subset in vivo induced genes, including not only genes involved in the biosynthesis of branched-chain amino acids, but also other genes that are induced during infection of the natural host. These results suggest that limitation of branched-chain amino acids may be one of an array of environmental cues responsible for the induction of virulence-associated genes in A. pleuropneumoniae.


Effective cervical neoplasia detection with a novel optical detection system: a randomized trial.
To assess whether the use of a novel optical detection system (ODS) as an adjunct to colposcopy increases the detection of biopsy-confirmed CIN 2,3. This is a multicenter two-arm randomized trial comparing colposcopy alone with colposcopy plus a pre-commercial ODS system that utilizes fluorescence, white light tissue reflectance, and cervical video imaging. Patients were recruited from 13 colposcopy clinics in a variety of practice settings. 2299 women referred for the evaluation of an abnormal cervical cytology were randomized with stratification by cytology; subsequently 113 women were excluded for a variety of reasons. The main study outcomes were differences in true-positive rates (CIN 2,3 and cancer identified) and false-positive rates between the study arms. The true-positive (TP) rates were 14.4% vs. 11.4% (p=0.035, one-sided) for the combined colposcopy and ODS arm compared to colposcopy-only arm, respectively, in women with either an atypical squamous cell (ASC) or low-grade squamous intraepithelial lesion (LSIL) cytology result. TP rates were similar between the two arms among women referred for the evaluation of HSIL. The 26.5% gain in true-positives observed with the use of ODS and colposcopy among women referred for an ASC or LSIL cytology was achieved with only a fractional increase in number of biopsies obtained per patient (0.30) and a modest increase in false-positive rate (4%). In the combined colposcopy and ODS arm among women with ASC or LSIL, the PPV of biopsies indicated by ODS was 15.0% and the PPV of biopsies indicated by colposcopy was 15.2%. Joint hypothesis testing indicates that ODS and colposcopy provides benefit compared to colposcopy alone among women with ASC or LSIL. Combining ODS with colposcopy provides a clinically meaningful increase in the detection of CIN 2,3 in women referred for the evaluation of mildly abnormal cytology results.


PCR-SSO typing for HLA-DRB alleles.
Polymerase chain reaction (PCR) amplification of the second exon of DRB genes from genomic DNA is described. Sequence-specific oligonucleotide (SSO) probes have been designed to allow for the typing of DRB alleles. The methods are described in detail and the results of a trial on both homozygous typing cells and restriction fragment length polymorphism (RFLP)-typed local caucasoid controls are given. The ease of use of this form of DRB typing is emphasized and potential complications are discussed.


PPAR{alpha} attenuates the proinflammatory response in activated mesangial cells.
The activated mesangial cell is an important therapeutic target for the control of glomerulonephritis. The peroxisome proliferator-activated receptor alpha (PPARalpha) has attracted considerable attention for its anti-inflammatory effects; however, its roles in the mesangial cells remain unknown. To determine the anti-inflammatory function of PPARalpha in mesangial cells, wild-type and Ppara-null cultured mesangial cells were exposed to lipopolysaccharide (LPS). LPS treatment caused enhanced proinflammatory responses in the Ppara-null cells compared with wild-type cells, as revealed by the induction of interleukin-6, enhanced cell proliferation, and the activation of the nuclear factor (NF)-kappaB signaling pathway. In wild-type cells resistant to inflammation, constitutive expression of PPARalpha was undetectable. However, LPS treatment induced the significant appearance and substantial activation of PPARalpha, which would attenuate the proinflammatory responses through its antagonizing effects on the NF-kappaB signaling pathway. The induction of PPARalpha was coincident with the appearance of alpha-smooth muscle actin, which might be associated with the phenotypic changes of mesangial cells. Moreover, another examination using LPS-injected wild-type mice demonstrated the appearance of PPARalpha-positive cells in glomeruli, suggesting in vivo correlation with PPARalpha induction. These results suggest that PPARalpha plays crucial roles in the attenuation of inflammatory response in activated mesangial cells. PPARalpha might be a novel therapeutic target against glomerular diseases.


AIDS, partner notification and gender issues.
The interplay between public health, human rights, legal obligations and physicians' ethical concerns was revealed dramatically in Israel in recent cases involving reporting of the HIV positive status of patients. This paper reviews and critically analyses the decision-making process of Israeli Ethics Committees regarding HIV partner notification. One aim of this analysis is to suggest principles that may guide the decision in such cases. It is argued that the resolution concerning disclosure to partners be based on the Principle of Proportionality, taking into account the type of relationship between partner and patient, their cultural background and gender issues. The paper demonstrates the advantages of addressing such issues by professional multidisciplinary Ethics Committees, whose decisions can bring to bear the scope of relevant considerations.


The microRNA-7-mediated reduction in EPAC-1 contributes to vascular endothelial permeability and eNOS uncoupling in murine experimental retinopathy.
To investigate the consequences of oxidative stress and hypoxia on EPAC-1 expression during retinopathy. Oxygen-induced retinopathy was induced in mice and EPAC-1 expression investigated by immunofluorescence. In silico analyses were used to identify a link between EPAC-1 expression and microRNA-7-5p in endothelial cells and confirmed by western blot analyses on cells expressing microRNA-7-5p. In vitro, endothelial cells were either incubated at 2% oxygen or transfected with microRNA-7-5p, and the effects of these treatments on EPAC-1 expression, endothelial hyperpermeability and NO production were assessed. In the Ins2Akita mouse model, levels of EPAC-1 expression as well as microRNA-7-5p were assessed by qPCR. Endothelial nitric oxide synthase was assessed by immunoblotting in the Ins2Akita model. Hypoxia induces the expression of microRNA-7-5p that translationally inhibits the expression of EPAC-1 in endothelial cells, resulting in hyperpermeability and the loss of eNOS activity. Activation of EPAC-1 by the cAMP analogue 8-pCPT-2'-O-Me-cAMP reduced the sensitivity of EPAC-1 to oxidative stress and restored the endothelial permeability to baseline levels. Additionally, 8-pCPT-2'-O-Me-cAMP rescued eNOS activity and NO production. In mouse models of retinopathy, i.e., oxygen-induced retinopathy and the spontaneous diabetic heterozygous Ins2Akita mice, EPAC-1 levels are decreased which is associated with an increase in microRNA-7-5p expression and reduced eNOS activity. In retinopathy, EPAC-1 expression is decreased in a microRNA-7-mediated manner, contributing to endothelial dysfunction. Pharmacological activation of remnant EPAC-1 rescues endothelial function. Collectively, these data indicate that EPAC-1 resembles an efficacious and druggable target molecule for the amelioration of (diabetic) retinopathy.


Casein kinase II from Rana temporaria oocytes. Intracellular localization and activity during progesterone-induced maturation.
A homogeneous preparation of casein kinase II has been isolated from the ribosome-free extracts of Rana temporaria oocytes by means of chromatography on heparin-Sepharose, phosphocellulose and mono Q. The enzyme consists of three subunits with molecular mass of 43 kDa, 41 kDa and 29 kDa. The protein kinase was labelled with radioactive iodine and injected back into oocytes. As shown by histoautoradiography the enzyme forms a diffuse ring around the nucleus in the oocyte cytoplasm. A part of casein kinase II is found in informosomes. During oocytes maturation casein kinase II activity increases 7 h after progesterone administration and at the final stages of maturation (20-23 h). Cycloheximide blocks the second augmentation of kinase activity and does not influence the first one.


Neuromodulation to the Rescue: Compensation of Temperature-Induced Breakdown of Rhythmic Motor Patterns via Extrinsic Neuromodulatory Input.
Stable rhythmic neural activity depends on the well-coordinated interplay of synaptic and cell-intrinsic conductances. Since all biophysical processes are temperature dependent, this interplay is challenged during temperature fluctuations. How the nervous system remains functional during temperature perturbations remains mostly unknown. We present a hitherto unknown mechanism of how temperature-induced changes in neural networks are compensated by changing their neuromodulatory state: activation of neuromodulatory pathways establishes a dynamic coregulation of synaptic and intrinsic conductances with opposing effects on neuronal activity when temperature changes, hence rescuing neuronal activity. Using the well-studied gastric mill pattern generator of the crab, we show that modest temperature increase can abolish rhythmic activity in isolated neural circuits due to increased leak currents in rhythm-generating neurons. Dynamic clamp-mediated addition of leak currents was sufficient to stop neuronal oscillations at low temperatures, and subtraction of additional leak currents at elevated temperatures was sufficient to rescue the rhythm. Despite the apparent sensitivity of the isolated nervous system to temperature fluctuations, the rhythm could be stabilized by activating extrinsic neuromodulatory inputs from descending projection neurons, a strategy that we indeed found to be implemented in intact animals. In the isolated nervous system, temperature compensation was achieved by stronger extrinsic neuromodulatory input from projection neurons or by augmenting projection neuron influence via bath application of the peptide cotransmitter Cancer borealis tachykinin-related peptide Ia (CabTRP Ia). CabTRP Ia activates the modulator-induced current IMI (a nonlinear voltage-gated inward current) that effectively acted as a negative leak current and counterbalanced the temperature-induced leak to rescue neuronal oscillations. Computational modelling revealed the ability of IMI to reduce detrimental leak-current influences on neuronal networks over a broad conductance range and indicated that leak and IMI are closely coregulated in the biological system to enable stable motor patterns. In conclusion, these results show that temperature compensation does not need to be implemented within the network itself but can be conditionally provided by extrinsic neuromodulatory input that counterbalances temperature-induced modifications of circuit-intrinsic properties.


Vibrational spectra of dissociatively adsorbed D2O on Al-terminated α-Al2O3(0001) surfaces from ab initio molecular dynamics.
Water can adsorb molecularly or dissociatively onto different sites of metal oxide surfaces. These adsorption sites can be disentangled using surface-sensitive vibrational spectroscopy. Here, we model Vibrational Sum Frequency (VSF) spectra for various forms of dissociated, deuterated water on a reconstructed, Al-terminated α-Al2O3(0001) surface at submonolayer coverages (the so-called 1-2, 1-4, and 1-4' modes). Using an efficient scheme based on velocity-velocity autocorrelation functions, we go beyond previous normal mode analyses by including anharmonicity, mode coupling, and thermal surface motion in the framework of ab initio molecular dynamics. In this way, we calculate vibrational density of states curves, infrared, and VSF spectra. Comparing computed VSF spectra with measured ones, we find that relative frequencies of resonances are in quite good agreement and linewidths are reasonably well represented, while VSF intensities coincide not well. We argue that intensities are sensitively affected by local interactions and thermal fluctuations, even at such low coverage, while absolute peak positions strongly depend on the choice of the electronic structure method and on the appropriate inclusion of anharmonicity.


Keratitis following descemet's stripping endothelial keratoplasty (DSEK): Clinical features and outcome in early vs late presentation.
To compare the clinical presentation, risk factors, causative organisms, and final outcome of early- and late- onset microbial keratitis following Descemet's Stripping Endothelial Keratoplasty (DSEK). In a retrospective, comparative, case series, twenty-three (10 early-onset keratitis, 13 late-onset keratitis) cases were included for analysis from a single centre tertiary eye care setup. Data about demography, indication, clinical features, and outcome were collected for both the groups. Comparison of clinical presentation, risk factors, microbiology and final outcome were carried out. The most common indication was failed graft. While all patients with late-onset keratitis presented with ulcerative keratitis, 60% of early-onset keratitis presented with ulcerative keratitis. Four patients in the early-onset group had interface keratitis. Associated endophthalmitis was more in the early-onset compared to the late-onset group. Early-onset interface keratitis cases are mostly associated with donor-related infection. Gram-positive bacteria were the most common organisms isolated from both early- and late- onset infection. Major surgical procedures in both early- and late- onset keratitis included lenticule removal (n = 4) and therapeutic penetrating keratoplasty (n = 5). Failed graft is a major risk factor in post-DSEK keratitis. Interface keratitis and endophthalmitis are commonly observed in early-onset keratitis. A majority of the patients need surgical intervention.


The role of foster parents in helping young people develop emancipation skills.
The current focus on preparing youths in foster care for emancipation has largely ignored the critical role foster parents have always played in preparing youths to leave their homes and take their place as successful adults in our society. To assure that programs to enhance youths' skills and abilities to function responsibly are fully effective, they must include foster parents. In doing so, they will exponentially increase the hours of service and training available to eligible youths and develop a resource that will be available to future youths after funds are redirected. It is unrealistic, however, to expect foster parents to provide all of the help that most youths in foster care need. Foster family support and training must be seen as one dimension of an integrated approach that provides all youths with a variety of resources but is specific to the needs of each youth. With appropriate support and training, foster parents can assume professional responsibility for assuring that such plans are implemented, and that youths leaving foster care have what they need to emancipate successfully.


Enhanced expression of human endogenous retroviruses in new-onset type 1 diabetes: Potential pathogenetic and therapeutic implications.
Human endogenous retroviruses (HERVs) have been studied and proposed as relevant cofactors in several autoimmune diseases, including type 1 diabetes (T1D), though with controversial results and no study at disease onset. In order to gather further information on the potential role of HERVs in the development of T1D we assessed the transcription levels of pol genes of HERV-H, HERV-K, and HERV-W in peripheral leucocytes from 37 children and adolescents with new-onset T1D and 50 age-matched control subjects. A PCR real time Taqman amplification assay was used to evaluate HERV transcripts with normalisation of the results to glyceraldehyde-3-phosphate dehydrogenase. The expression levels of HERV-H-pol gene and HERV-W-pol gene were significantly higher in diabetic patients than in control subjects. Conversely, no significant difference emerged in the expression levels of HERV-K-pol gene between diabetic patients and controls. The activation of HERV-H and HERV-W in new-onset T1D suggests their importance in the pathogenesis of the disease and supports targeted therapeutic attempts to hinder their activation.


Body balance at static posturography in vestibular migraine.
Migraine is one of the most frequent and incapacitating headaches, with a high degree of impairment in quality of life. Its association with vestibular symptoms is common, including imbalance and postural instability. To evaluate the body balance of patients with vestibular migraine through a static posturography test. An experimental group of 31 patients with a medical diagnosis of vestibular migraine in the intercritical period of the disease, and a control group of 31 healthy individuals, matched for age and gender, were submitted to the eight sensory conditions of the Tetrax Interactive Balance System. The parameters analyzed were: stability index, which measures the amount of sway, global stability and ability to compensate postural modifications; weight distribution index, which compares deviations in weight distribution; synchronization index, which measures the symmetry in the weight distribution; postural sway frequency, which indicates the frequency range with more sway; and fall risk index, which expresses the probability of falls. The stability index was higher in the experimental group in all eight sensory conditions, with a significant difference between the groups in six of them. The weight distribution index was higher in the experimental group in all conditions, with a significant difference in three of them. The number of cases with preferential sway in F2-F4 was significantly higher in the experimental group in three conditions, and in F5-F6 in two, while the fall risk was significantly higher in the experimental group than in the control group. Patients with vestibular migraine showed compromised body balance at the static posturography test.


Combinatorial QSAR modeling of human intestinal absorption.
Intestinal drug absorption in humans is a central topic in drug discovery. In this study, we use a broad selection of machine learning and statistical methods for the classification and numerical prediction of this key end point. Our data set is based on a selection of 458 small druglike compounds with FDA approval. Using easily available tools, we calculated one- to three-dimensional physicochemical descriptors and used various methods of feature selection (best-first backward selection, correlation analysis, and decision tree analysis). We then used decision tree induction (DTI), fragment-based lazy-learning (LAZAR), support vector machine classification, multilayer perceptrons, random forests, k-nearest neighbor and Naïve Bayes analysis to model absorption ratios and binary classification (well-absorbed and poorly absorbed compounds). Best performance for classification was seen with DTI using the chi-squared analysis interaction detector (CHAID) algorithm, yielding corrected classification rate of 88% (Matthews correlation coefficient of 75%). In numeric predictions, the multilayer perceptron performed best, achieving a root mean squared error of 25.823 and a coefficient of determination of 0.6. In line with current understanding is the importance of descriptors such as lipophilic partition coefficients (log P) and hydrogen bonding. However, we are able to highlight the utility of gravitational indices and moments of inertia, reflecting the role of structural symmetry in oral absorption. Our models are based on a diverse data set of marketed drugs representing a broad chemical space. These models therefore contribute substantially to the molecular understanding of human intestinal drug absorption and qualify for a generalized use in drug discovery and lead optimization.


[Distal osteotomy of the metatarsal bones in the treatment of metatarsalgia].
Authors review briefly the development of the principles of metatarsal osteotomies and the basic concepts that seem to be the most suitable in the choice of the type and execution of the operation. The effectiveness of the surgical treatment is stressed if the following viewpoints are considered: 1. Synchronous correction of the rays II, III, and IV. 2. Simultaneously achieved abbreviation and forming of the arch. 3. Instead of internal fixation transversal lifting bandage with early weight bearing. The finding, according which, beside the telescope osteotomy of Helal, Wolf's metatarsal osteotomy with axial deviation is also a valuable alternative, is supported by the follow-up of their own 2 years material.


Reduction in the earthworm metabolomic response after phenanthrene exposure in soils with high soil organic carbon content.
We evaluated the correlation between soil organic carbon (OC) content and metabolic responses of Eisenia fetida earthworms after exposure to phenanthrene (58 ± 3 mg/kg) spiked into seven artificial soils with OC contents ranging from 1 to 27% OC. Principal component analysis of (1)H nuclear magnetic resonance (NMR) spectra of aqueous extracts identified statistically significant differences in the metabolic profiles of control and phenanthrene-exposed E. fetida in the 1% OC soil only. Partial least squares analysis identified a metabolic response in the four soils with OC values ≤11% which was well correlated to estimated phenanthrene porewater concentrations. The results suggest that the higher sorption capability of high OC soils decreased the bioavailability of phenanthrene and the subsequent metabolic response of E. fetida.


The GAPs, GEFs, GDIs and…now, GEMs: New kids on the heterotrimeric G protein signaling block.
The canonical process of activation of heterotrimeric G proteins by G protein coupled receptors (GPCRs) is well studied. Recently, a rapidly emerging paradigm has revealed the existence of a new, non-canonical set of cytosolic G protein modulators, guanine exchange modulators (GEMs). Among G proteins regulators, GEMs are uniquely capable of initiating pleiotropic signals: these bifunctional modulators can activate cAMP inhibitory (Gi) proteins and inhibit cAMP-stimulatory (Gs) proteins through a single short evolutionarily conserved module. A prototypical member of the GEM family, GIV/Girdin, integrates signals downstream of a myriad of cell surface receptors, e.g., growth factor RTKs, integrins, cytokine, GPCRs, etc., and translates these signals into G protein activation or inhibition. By their pleiotropic action, GIV and other GEMs modulate several key pathways within downstream signaling network. Unlike canonical G protein signaling that is finite and is triggered directly and exclusively by GPCRs, the temporal and spatial features of non-canonical activation of G protein via GIV-family of cytosolic GEMs are unusually relaxed. GIV uses this relaxed circuitry to integrate, reinforce and compartmentalize signals downstream of both growth factors and G proteins in a way that enables it to orchestrate cellular phenotypes in a sustained manner. Mounting evidence suggests the importance of GIV and other GEMs as disease modulators and their potential to serve as therapeutic targets; however, a lot remains unknown within the layers of the proverbial onion that must be systematically peeled. This perspective summarizes the key concepts of the GEM-dependent G protein signaling paradigm and discusses the multidisciplinary approaches that are likely to revolutionize our understanding of this paradigm from the atomic level to systems biology.


Specific leukotriene receptors couple to distinct G proteins to effect stimulation of alveolar macrophage host defense functions.
Leukotrienes (LTs) are lipid mediators implicated in asthma and other inflammatory diseases. LTB(4) and LTD(4) also participate in antimicrobial defense by stimulating phagocyte functions via ligation of B leukotriene type 1 (BLT1) receptor and cysteinyl LT type 1 (cysLT1) receptor, respectively. Although both Galpha(i) and Galpha(q) proteins have been shown to be coupled to both BLT1 and cysLT1 receptors in transfected cell systems, there is little known about specific G protein subunit coupling to LT receptors, or to other G protein-coupled receptors, in primary cells. In this study we sought to define the role of specific G proteins in pulmonary alveolar macrophage (AM) innate immune responses to LTB(4) and LTD(4). LTB(4) but not LTD(4) reduced cAMP levels in rat AM by a pertussis toxin (PTX)-sensitive mechanism. Enhancement of FcgammaR-mediated phagocytosis and bacterial killing by LTB(4) was also PTX-sensitive, whereas that induced by LTD(4) was not. LTD(4) and LTB(4) induced Ca(2+) and intracellular inositol monophosphate accumulation, respectively, highlighting the role of Galpha(q) protein in mediating PTX-insensitive LTD(4) enhancement of phagocytosis and microbicidal activity. Studies with liposome-delivered G protein blocking Abs indicated a dependency on specific Galpha(q/11) and Galpha(i3) subunits, but not Galpha(i2) or G(beta)gamma, in LTB(4)-enhanced phagocytosis. The selective importance of Galpha(q/11) protein was also demonstrated in LTD(4)-enhanced phagocytosis. The present investigation identifies differences in specific G protein subunit coupling to LT receptors in antimicrobial responses and highlights the importance of defining the specific G proteins coupled to heptahelical receptors in primary cells, rather than simply using heterologous expression systems.


Transition of R factor NR1 in Proteus mirabilis: molecular structure and replication of NR1 deoxyribonucleic acid.
The structure of R factor NR1 DNA in Proteus mirabilis has been studied by using the techniques of CsCl density gradient centrifugation, sedimentation in neutral and alkaline sucrose gradients, and electron microscopy. It has been shown that the nontransitioned form of NR1 DNA isolated from P. mirabilis cultured in drug-free medium is a37-mum circular deoxyribonucleic acid (DNA) with a density of 1.712 g/ml in a neutral CsCl gradient. This circular molecule is a composite structure consisting of a 29-mum resistance transfer factor containing the tetracycline-resistance genes (RTF-TC) and an 8-mum r-determinants component conferring resistance to chloramphenicol (CM), streptomycin/spectinomycin, and the sulfonamides. There are one to two copies of NR1 per chromosome equivalent of DNA in exponential-phase cells cultured in Penassay broth. After growth of PM15/NR1 in medium containing 100 mug of CM per ml, the density of the NR1 DNA increased from 1.712 g/ml to approximately 1.718 g/ml and the proportion of NR1 DNA relative to the chromosome is amplified about 10-fold. The changes in R factor DNA structure which accompany this phenomenon (termed the transition) have been studied. DNA density profiles of the transitioned NR1 DNA consist of a 1.718 g/ml band which is skewed toward the less dense side. The transitioned NR1 DNA consists of molecules containing the RTF-TC element attached to multiple copies of r-determinants DNA (poly-r-determinant R factors) and multimeric and monomeric autonomous r-determinants structures. Poly-r-determinant R factors have a density intermediate between the basic composite structure (1.712 g/ml) and r-determinants DNA (1.718 g/ml). These species presumably account for the skewing of the 1.718-g/ml DNA band toward the less dense side. When transitioned cells are subsequently cultured in drug-free medium, poly-r-determinant R factors and autonomous poly-r-determinants undergo dissociation to form smaller structures containing fewer copies of r-determinants. This process continues until, after prolonged growth in drug-free medium the NR1 DNA returns to the nontransitioned state which consists of an RTF-TC and a single copy of r-determinants.


[Vascularization of the cervical trachea and its clinical relevance. A scanning electron microscopy study on corrosion casts].
The angioarchitecture of the cervical trachea of the rat as a model was studied using scanning electron microscopy of vascular corrosion casts. Four different types of vascular pattern are described. 1. Supplying and draining vessels of the first order (Superior and inferior thyroid arteries, and inferior thyroid veins) situated within the peritracheal tissue at the lateral sides of the trachea. 2. The vessels arising from them, which have a horizontal course and lie within the intercartilaginous membrane (vessels of the second order). 3. The vessels of the third order branching from those of the second order, perforating the intercartilaginous membrane and again running vertically within the tracheal mucosa. 4. Vessels of the fourth order forming the capillary plexus of the tracheal mucosa, consisting of irregular (pars fibrocartilaginea) or rectangular (pars membranacea) meshes. The clinical relevance of the vascular patterns of the trachea is discussed in respect to ischemic tracheal lesions.


Severe persistent unremitting dermatitis, chronic diarrhea and hypoalbuminemia in a child; Hartnup disease in setting of celiac disease.
Celiac disease (CD) is a complex autoimmune disorder that can lead to an inflammatory small intestinal villous atrophy and malabsorption. Hartnup disease is an autosomal recessive disorder caused by increased urinary excretion of neutral amino acids. Co-occurrence of Hartnup disease and CD is extremely rare with only a single case reported. We report a 3-year girl with chronic diarrhea, Hypoalbuminemia and exfoliative erythema. She was diagnosed with celiac disease, which did not improve on gluten free diet. Hartnup disease was suspected and was confirmed by neutral aminoaciduria. Niacin was started and followed by dramatic improvement. Presence of Celiac and Hartnup disease in single individual is very rare. Complete nutritional assessment of refractory celiac patient can reveal underlying nutritional deficiency.


p-NO2-Bn-H4neunpa and H4neunpa-Trastuzumab: Bifunctional Chelator for Radiometalpharmaceuticals and 111In Immuno-Single Photon Emission Computed Tomography Imaging.
Potentially nonadentate (N5O4) bifunctional chelator p-SCN-Bn-H4neunpa and its immunoconjugate H4neunpa-trastuzumab for 111In radiolabeling are synthesized. The ability of p-SCN-Bn-H4neunpa and H4neunpa-trastuzumab to quantitatively radiolabel 111InCl3 at an ambient temperature within 15 or 30 min, respectively, is presented. Thermodynamic stability determination with In3+, Bi3+, and La3+ resulted in high conditional stability constant (pM) values. In vitro human serum stability assays have demonstrated both 111In complexes to have high stability over 5 days. Mouse biodistribution of [111In][In(p-NO2-Bn-neunpa)]-, compared to that of [111In][In(p-NH2-Bn-CHX-A″-diethylenetriamine pentaacetic acid (DTPA))]2-, at 1, 4, and 24 h shows fast clearance of both complexes from the mice within 24 h. In a second mouse biodistribution study, the immunoconjugates 111In-neunpa-trastuzumab and 111In-CHX-A″-DTPA-trastuzumab demonstrate a similar distribution profile but with slightly lower tumor uptake of 111In-neunpa-trastuzumab compared to that of 111In-CHX-A″-DTPA-trastuzumab. These results were also confirmed by immuno-single photon emission computed tomography (immuno-SPECT) imaging in vivo. These initial investigations reveal the acyclic bifunctional chelator p-SCN-Bn-H4neunpa to be a promising chelator for 111In (and other radiometals) with high in vitro stability and also show H4neunpa-trastuzumab to be an excellent 111In chelator with promising biodistribution in mice.


Classification of Multiple Finger Motions During Dynamic Upper Limb Movements.
To better restore human hand function, advanced hand prostheses should be able to deal with a variety of daily living conditions. In this paper, we addressed myoelectric signal variations introduced by different muscle contractions, dynamic arm movements, and outer interfering forces in the practice of pattern recognition-based myoelectric control schemes. We examined four different training paradigms (data-collection protocols) and quantified their effectiveness for obtaining a robust classification. We further depicted the classification accuracy according to different arm/wrist motion primitives. Our results indicate the training paradigm that collects myoelectric signals on dynamic arm postures and varying muscular contractions (DPDE) can largely mitigate the motions' misclassification rate. The misclassification rate of finger motions seems to highly correlate to wrist pronation and supination, rather than different arm positions. Combining proprioceptive information, such as the hand's orientation, with myoelectric signals for classification only slightly alleviates the misclassification rate.


Polyamine requirements in nicotinamide-stimulated beta-cell differentiation in fetal porcine islet-like cell clusters.
The impact of nicotinamide on regulation of cell replication and hormone production by fetal porcine islet-like cell clusters (ICCs) containing a low fraction of beta-cells was investigated. For this purpose, ICCs were produced in tissue culture for 4 days in the presence or absence of nicotinamide (10 mM). ICCs formed in the presence of nicotinamide showed increased rates of (pro)insulin biosynthesis, contained more insulin, and displayed elevated contents of polyamines when compared with untreated ICCs. Immunocytochemical analyses of autoradiographed ICCs disclosed that nicotinamide expanded the relative size of the beta-cell population, and that the vitamin increased DNA synthesis of non-beta-cells only. The possibility that the effects of nicotinamide were conveyed by the increased polyamine content was explored by giving nicotinamide together with inhibitors of rate-limiting enzymes of polyamine biosynthesis, a maneuver that precluded the increases in polyamines of whole ICCs. Although this treatment prevented the increases in beta-cell population size, insulin production, and insulin content evoked by nicotinamide, the elevated cell replication nonetheless persisted. We conclude that the stimulatory effects of nicotinamide on insulin production and content by fetal porcine ICCs result from neoformation of beta-cells through differentiation. Since these effects were prevented by blocking the increased polyamine content, it is suggested that a stimulated synthesis of polyamines may be an important event in mediating the differentiating action of nicotinamide.


Epigenetic Regulation of TRAIL Signaling: Implication for Cancer Therapy.
One of the main characteristics of carcinogenesis relies on genetic alterations in DNA and epigenetic changes in histone and non-histone proteins. At the chromatin level, gene expression is tightly controlled by DNA methyl transferases, histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyl-binding proteins. In particular, the expression level and function of several tumor suppressor genes, or oncogenes such as c-Myc, p53 or TRAIL, have been found to be regulated by acetylation. For example, HATs are a group of enzymes, which are responsible for the acetylation of histone proteins, resulting in chromatin relaxation and transcriptional activation, whereas HDACs by deacetylating histones lead to chromatin compaction and the subsequent transcriptional repression of tumor suppressor genes. Direct acetylation of suppressor genes or oncogenes can affect their stability or function. Histone deacetylase inhibitors (HDACi) have thus been developed as a promising therapeutic target in oncology. While these inhibitors display anticancer properties in preclinical models, and despite the fact that some of them have been approved by the FDA, HDACi still have limited therapeutic efficacy in clinical terms. Nonetheless, combined with a wide range of structurally and functionally diverse chemical compounds or immune therapies, HDACi have been reported to work in synergy to induce tumor regression. In this review, the role of HDACs in cancer etiology and recent advances in the development of HDACi will be presented and put into perspective as potential drugs synergizing with TRAIL's pro-apoptotic potential.


[Association between polycyclic aromatic hydrocarbons exposure levels and nucleoplasmic bridge and nuclear bud frequencies in coke-oven workers].
To seek new effect biomarkers as to evaluating the chromosomal damage in peripheral blood lymphocytes in coke-oven workers who were exposed to polycyclic aromatic hydrocarbons (PAHs). One hundred and fifty-eight coke-oven workers and 69 controls were recruited in this study. Nucleoplasmic bridges and nuclear buds were counted as indicators of chromosomal damage in terms of cytokinesis-block micronucleus (CBMN) test. Occupational history, age, sex, smoking and alcohol using status of all subjects were collected by questionnaire. Frequencies of nucleoplasmic bridge in coke-oven workers were (9.41 +/- 3.73)% per hundred, and the frequencies of nuclear buds were (7.13 +/- 4.01)% per hundred, which were significantly higher (P < 0.01) than those of controls (1.88 +/- 1.49)% per hundred and (2.20 +/- 1.73)% per hundred respectively. The dose-effect relationships between nucleoplasmic bridges or nuclear buds and PAHs exposure levels were identified. Compared with male coke-oven workers, female workers had less nucleoplasmic bridges or nuclear buds. No effects of age, smoking and alcohol using were found on nucleoplasmic bridges or nuclear buds among coke-oven workers. Nucleoplasmic bridges and nuclear buds might be effect biomarkers in coke-oven workers.


Histidine mutagenesis of Arabidopsis thaliana pyruvate dehydrogenase kinase.
Pyruvate dehydrogenase kinase (PDK) is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex (PDC). Analysis of the primary amino-acid sequences of PDK from various sources reveals that these enzymes include the five domains characteristic of prokaryotic two-component His-kinases, despite the fact that PDK exclusively phosphorylates Ser residues in the E1alpha subunit of the PDC. This seeming contradiction might be resolved if the PDK-catalyzed reaction employed a phospho-His intermediate. The results from pH-stability studies of autophosphorylated Arabidopsis thaliana PDK did not provide any support for a phospho-His intermediate. Furthermore, site-directed mutagenesis of the two most likely phosphotransfer His residues (H121 and H168) did not abolish either PDK autophosphorylation or the ability to transphosphorylate E1alpha. Thus, PDK is a unique type of protein kinase having a His-kinase-like sequence but Ser-kinase activity.


Myocardial sensitivity to isoproterenol following abrupt propranolol withdrawal in conscious dogs.
The sensitivity of the cardiovascular system to isoproterenol following abrupt cessation of propranolol administration was studied in chronically instrumented conscious dogs pretreated orally with propranolol for 14 days. The effects of intravenous isoproterenol on heart rate, blood pressure, and mean velocity of circumferential fiber shortening (Vcf) were determined before and during propranolol administration and then at 12 hr intervals following drug withdrawal. During propranolol administration, all dose-response curves to isoproterenol were predictably shifted to the right. Twenty-four hours following propranolol withdrawal, when plasma levels of drug averaged only 7 ng/ml, the chronotropic response to isoproterenol remained significantly inhibited. In contrast, the Vcf response recovered rapidly and at 24 hr equaled the pretreatment control response. Furthermore, between 36 and 60 hr, when plasma propranolol levels averaged less than 1 ng/ml, the Vcf dose-response curve to isoproterenol was shifted to the left of control prior to returning to the pretreatment level. This leftward displacement of the Vcf response curve was not accompanied by a parallel change in the heart rate response or in afterload. Plasma norepinephrine levels were measured throughout the study and were not altered during drug treatment or following withdrawal. Thus, the data indicate that abrupt cessation of propranolol administration is associated with a period of increased myocardial sensitivity to at least the inotropic effects of isoproterenol and that abrupt withdrawal does not result in acute changes in sympathetic nervous system activity.


Comparison of open and laparoscopic pyeloplasty in ureteropelvic junction obstruction surgery: report of 49 cases.
This study aimed to evaluate laparoscopic dismembered pyeloplasty compared with open surgery and to determine whether the morbidity and outcome rates are different in each of these techniques. We report our 10-year experience with open and laparoscopic pyeloplasty at one istitution. From February 1999 to October 2010, 49 patients with ureteropelvic junction obstruction were assigned into two groups. 25 patients underwent open surgical pyeloplasty (period 1999-2010) and 24 underwent laparoscopic pyeloplasty (period 2004-2010). 25 patients undergoing open pyeloplasty had a retroperitoneal flank approach. Of the 24 laparoscopic cases 18 had a transperitoneal retrocolic access, 1 had a transperitoneal transmesocolic access and 5 had a retroperitoneal access. In all 49 cases an Anderson-Hynes dismembered pyeloplasty was used. We retrospectively compared the operative time, hospital stay, perioperative complications and follow-up of the two groups. Clinical symptoms were assessed before and after surgery, subjectively. Patients dermographic data were similar between the two groups with mean age of 42 years (range 6-78) and with a male/female ratio of 1:1.45. A crossing vessel could be identified in 37.5% (9/24) with laparoscopy vs. 32% (8/25) in open surgery. Compared with open procedures, laparoscopic procedures were associated with a longer mean operating time (274 vs 143 min), a shorter mean hospital stay (9.9 vs 15.8 day) and the perioperative complication rates were 16.7% for laparoscopic pyeloplasties and 20% for open pyeloplasties. The success rates were 90.5% for laparoscopy and 90.9% for open surgery. Average follow-up was 40.9 month for the laparoscopic group and 72.3 month for the open group. Failed procedures showed no improvement in loin pain or obstruction. The efficacy (in term of success rate and perioperative complications) of laparoscopic pyeloplasty is comparable to that of open pyeloplasty, with shorter mean hospital stay and better cosmetic results. These findings may suggest, that the laparoscopic dismembered pyeloplasty has the potential to replace open surgery and may be considered the first option for the treatment of ureteropelvic junction obstruction in expert hands.


A new technique for positioning tangential fields.
A technique that eliminates the use of a mechanical "breast-bridge" for positioning tangential fields for treatment of the intact breast or chest wall has been developed. Treatment set-up parameters are determined using measuring capabilities (gantry angles and source-skin distances) available on a standard simulator unit. A programmable scientific calculator is used to determine field geometry from polar coordinates for various points on the patient's skin. The calculator program determines the field size, a depth and lateral shift from a skin reference point to the isocenter for the tangential fields, and the gantry angles. The program provides additional information which facilitates the simulation process: First, the coordinates of the isocenter for the tangential fields are expressed relative to couch coordinates for an initial arbitrary isocenter so that the "auto go to" capability available on some simulators can be used. Second, the coordinates of the medial and lateral entry points can be edited when the first set of tangents are not accepted. This part of the program allows quick and efficient adjustment of the fields to obtain adequate treatment volume coverage and a minimum of irradiated lung or heart. Simulation of more than 300 patients has shown the technique to be a practical and efficient method for positioning tangential fields for breast or chest wall irradiation. The technique described here takes full advantage of the capabilities of the new generation of computer controlled simulators, and offers an alternative to previous methods employing a mechanical "breast-bridge."


Variability in aphasic patients' response times.
Response time studies of acquired language disorders are plagued by tremendous variability in patients' response times. In this brief report we demonstrate how variability itself may provide informative data. Lexical decision response times, generated by nine patients, illustrate how within-patient variability may estimate stability in cognitive dynamics.


Increase in Candida Parapsilosis Candidemia in Cancer Patients.
This study aimed to identify the risk factors of candidemia and asses possible clinically significant differences between Candida parapsilosis and other Candida species in a Chinese tertiary cancer center over six years. A total of 323 cancer patients were enrolled and analyzed from 2012 to 2018. Among the isolates, the species most frequently isolated was C. parapsilosis (37.15%, 120/323), and C. albicans only accounted for 34.37%. Based on statistical analysis, when candidemia patients who had C. parapsilosis were compared with other Candida spp., the following factors were found to be significantly associated with C. parapsilosis fungemia: parenteral nutrition (p < 0.001), neutropenia (p < 0.001), receipt of chemotherapy (p = 0.002), and previous antifungal use (p < 0.001). Parenteral nutrition was a factor that independently predicted C. parapsilosis candidemia (OR, 0.183; 95% CI, 0.098-0.340; p < 0.001).In short, C. parapsilosis as the leading non-albicans Candida spp. isolates in candidemia are posing a major threat for cancer patients. The study highlights the urgent need to evaluate the possibility of development of C. parapsilosis candidemia in cancer patients exposed to these risk factors effective and prevention strategies against this causative agent transmitted through nosocomial route should be implemented.


[Combined scores of 64 multi-slice CT perfusion characteristics for evaluating solitary pulmonary nodules].
To study the bloody flow mode and the perfusion feature of solitary pulmonary nodules (SPN) on 64 multi-slice CT, and to evaluate the diagnostic value of combined scores in SPN. Fifty-two patients with SPN proved by pathology or follow-up underwent dynamic enhancement CT. Perfusion characteristics, including permeability (P), blood flow, blood volume, patlak blood volume, patlak R square (PRS), patlak residual, peak enhancement, perfusion curve, and false color image were analyzed by the body perfusion software. Perfusion characteristics were compared between benign and malignant nodules. Combined scores composed of significant difference observed parameters were used to differentiate benign or malignant SPN. There were significant differences in the enhancement values at 20, 22, 24, 25, 26, 28, 30, and 34s, PRS, I or II type perfusion curve, and marginal uncomplete enhancement or patchy complete enhancement at 34s between benign and malignant SPN. With the multi-variant combined score > 0.5 as the threshold value to differentiate benign and malignant SPN, its sensitivity and specificity was 94.3% and 41.2%, respectively. The combined scores of 64 multi-slice CT can help differentiate the benign or malignant SPN.


Renal tubular acidosis type 2 with Fanconi's syndrome, osteomalacia, osteoporosis, and secondary hyperaldosteronism in an adult consequent to vitamin D and calcium deficiency: effect of vitamin D and calcium citrate therapy.
To describe a unique example of renal tubular acidosis type 2 (RTA 2) in conjunction with Fanconi's syndrome and osteomalacia consequent to vitamin D and calcium deficiency in an adult without underlying gastrointestinal disease. We review the clinical, hormonal, histomorphometric, and micro-computed tomographic findings and the response to therapy with vitamin D and calcium in our patient. On admission, a 33-year-old African American woman had the following laboratory findings: serum ionized calcium 3.8 mg/dL (0.95 mmol/L), venous pH 7.26, bicarbonate 20 mEq/L, chloride 111 mEq/L, alkaline phosphatase 1,192 U/L (20.26 microkat/L) (normal, 40 to 136 U/L), 25-hydroxyvitamin D <5 ng/mL (<12 nmol/L) (normal, 10 to 60 ng/mL), parathyroid hormone 1,620 pg/mL (165.2 pmol/L) (normal, 10 to 60 pg/mL), aldosterone 68.4 ng/dL (1,894.7 pmol/L) (normal, 4.5 to 35.4 ng/dL), supine plasma renin activity 19.8 ng/mL per hour (5.35 ng/L per second) (normal, 0.5 to 1.8 ng/mL per hour), and aminoaciduria. A lumbar spine bone density T-score was -4.6, and a femoral neck T-score was -4.9. An undecalcified tetracycline-labeled bone biopsy specimen showed severe osteomalacia, severe osteoporosis, and peritrabecular fibrosis. A small intestinal biopsy revealed normal findings. Results of an ammonium chloride loading test and a bicarbonate infusion test were consistent with RTA 2. After 24 months of vitamin D and calcium therapy, results of serum and urine chemistry studies and bicarbonate infusion normalized. The lumbar spine T-score improved to -2.0, and the femoral neck T-score improved to -2.7. Bone biopsy specimens demonstrated resolution of the osteomalacia. Nutritional vitamin D and calcium deficiency may cause RTA 2, Fanconi's syndrome, and osteomalacia in adults as well as in children.


Genetic polymorphisms of Y-chromosome short tandem repeats (Y-STRs) in a male population from Golestan province, Iran.
Short Tandem Repeats (STRs), which are located out of pseudo-autosomal parts of the human Y chromosome and passed-down from fathers to the male offspring in a non-recombinant form, are regarded as appropriate markers for forensic purposes and evolutionary investigations. Few studies concerned the genotyping of Y chromosome short tandem repeats (Y-STRs) among the ethnic groups of the north of Iran, especially the province of Golestan which is a multiethnic region of Iran. Thus, in this work we investigated the frequency of Y-STR haplotypes among the male population from Golestan province, to elucidate their identity and kinship patterns. A total number of 106 unrelated male individuals participated in this study. Genomic DNA was extracted from blood samples and the multiplex polymerase chain reaction was employed to amplify DNA fragments. Genotyping was performed using capillary electrophoresis and, finally, allele polymorphisms, haplotype diversity (HD) and haplotype discrimination capacity (DC) were determined using GenAlEXv6.5 and Arlequin v5.3.2 software and compared to other regions of Iran. A total number of 87 unique haplotypes were determined. The highest and least allelic polymorphism was observed for the DYS385b and DYS391 loci, respectively. HD and DC were 0.9962 and 0.8207, respectively. In the case of locus with the least allelic variation, we didn't observe any difference between the Gilan and Golestan but there was a difference between the Golestan and Mazandaran provinces. Our results indicated the efficiency of Y-STRs to be used as genetic markers for forensic medicine, and also the evolutionary comparison of different ethnic groups of Golestan, Iran. Also, a low genetic distance between the population of Golestan with other northern provinces was noticed.


A polydimethylsiloxane/deep eutectic solvent sol-gel thin film sorbent and its application to solid-phase microextraction of parabens.
A novel, efficient and reproducible thin-film solid-phase microextraction method using the polydimethylsiloxane/deep eutectic solvent sol-gel as coating material was developed for preconcentration of parabens from environmental samples. New sorbent materials consisting of polydimethylsiloxane with nine new synthesized deep eutectic solvents were prepared by the sol-gel method, and these materials were used to prepare thin film coatings on a mesh support. Among obtained compounds, the highest efficiency in the extraction of parabens was demonstrated by a sorbent consisting of trihexyltetradecylphosphonium chloride and n-docosanol in a molar ratio 1:2 mixed with polydimethylsiloxane. For the proposed method, the parameters affecting the extraction efficiency of parabens were optimized, including the coating material type based on polydimethylsiloxane/deep eutectic solvent, the sample volume, the salting-out effect, the pH of the sample, the extraction time, the desorption solvent and time. The limits of detection and quantitation were from 0.023 to 0.062 ng mL-1 and 0.076-0.201 ng mL-1, respectively, and the enrichment factors ranged from 174 to 186. Under optimal conditions, the proposed method based on measurements for river and lake water achieved good precision between 2.7 and 5.9% and recovery ranging from 79.1 to 88.1%. The developed method was successfully applied to determine trace levels of parabens in the samples of surface waters collected from rivers and lakes.


Dermatologic therapy in pregnancy.
Patients present during pregnancy with a variety of dermatologic conditions, most of which can be treated conservatively with topical medication by a primary obstetrician if he or she is familiar with common treatment options. Patients with moderate to severe forms of dermatologic disease or those requiring systemic therapy should be treated in consultation with a dermatologist. Dermatologic surgery can be performed safely in the second trimester using local anesthesia if needed.


Fibrin glue in thyroid and parathyroid surgery: is under-flap suction still necessary?
The introduction of fibrin sealants has brought into question the necessity of routinely placing suction drains. We conducted a retrospective study to determine whether fibrin sealants are comparable to traditional drains in terms of length of hospital stay and hematoma prevention. We evaluated 124 patients who had undergone thyroidectomy and 47 patients who had undergone parathyroidectomy. Of these, 22 thyroid surgery patients and 10 parathyroid surgery patients had their incisions closed without a drain after the application of fibrin glue. We found that the use of fibrin glue resulted in a statistically significant decrease in the length of hospital stay following both types of surgery (p = 0.033 and p = 0.022, respectively). Two hematomas in the drain group required immediate surgical evacuation; in both of these patients, the suction was clotted and ineffective. One minor hematoma occurred in the fibrin glue group, and it was opened at the bedside 24 hours after surgery. We conclude that fibrin sealants offer a comparative advantage over under-flap suction in both thyroid and parathyroid surgery. Also, fibrin glue is less expensive, and its use obviates the discomfort felt by patients when a drain is removed.


[Effect of the concomitant administration of indomethacin or ibuprofen on amikacin pharmacokinetics in premature newborns].
To evaluate whether the concomitant administration of ibuprofen or indomethacin plus amikacin may alter the latter drug s pharmacokinetic parameters, and hence amikacin plasma levels. Retrospective cohort study performed by reviewing the medical records of premature children with persistent ductus arteriosus receiving amikacin and ibuprofen, or amikacin and indomethacin. They were divided up into three groups: group 1: treatment with amikacin went before indomethacin or ibuprofen; group 2: simultaneously treated with amikacin and indomethacin; group 3: simultaneously treated with amikacin and ibuprofen. Pharmacokinetic parameters, distribution volume, and amikacin clearance were measured using the PKS program (a non-linear regression method). Half life was determined from previous parameters. Twenty-eight patients were included. No statistically significant differences were found among pharmacokinetic parameters corresponding to each study group. Further studies are needed with a greater number of patients and currently recommended doses to assess the influence of indomethacin and ibuprofen in the pharmacokinetics of amikacin in premature children with persistent ductus arteriosus.


Efficacy of mobilisation with movement in chronic shoulder pain: protocol for a systematic review and meta-analysis of controlled trials.
Shoulder pain affects approximately one in four adults and is thus one of the most common musculoskeletal problems. Only 50% of patients who begin treatment for shoulder pain are cured within 6 months. There is a need for systematic reviews to estimate the effectiveness of shoulder treatments. We decided to evaluate the effect of mobilisation with movement (MWM) on chronic shoulder pain in a systematic review. The review will include controlled trial articles identified via five electronic databases (PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Physiotherapy Evidence Database and Cochrane Central Register of Controlled Trials), reference lists, citations searches and experts in the field. Only controlled trials involving participants with a mean duration of pain of ≥3 months, in which the effectiveness of MWM has been compared with non-invasive treatments, sham mobilisation or wait-and-see will be included. The included trials will be synthesised with random effects meta-analyses. Risk-of-bias will be assessed with the Physiotherapy Evidence Database 0-10 point scale. The review does not require ethics approval as it is based on anonymised data from trial reports. The results of the review will be disseminated through a peer-reviewed publication. CRD42018109380.


A vacuum ultraviolet pulsed field ionization-photoelectron study of cyanogen cation in the energy range of 13.2-15.9 eV.
The vacuum ultraviolet pulsed field ionization-photoelectron and photoionization efficiency spectra of NCCN have been measured in the energy region of 13.25-17.75 eV. The analyses of these spectra have provided accurate ionization energy (IE) values of 13.371+/-0.001, 14.529+/-0.001, 14.770+/-0.001, and 15.516+/-0.001 eV for the formation of NCCN(+) in the X(2)Pi(g), A(2)Sigma(g) (+), B(2)Sigma(u) (+), and C(2)Pi(u) states, respectively. The ionization energy [NCCN(+)(B(2)Sigma(u) (+))] value determined here indicates that the origin of the NCCN(+)(B(2)Sigma(u) (+)) state lies lower in energy by 25 meV than previously reported. A set of spectroscopic parameters for NCCN(+)(X(2)Pi(g)) has been calculated using high level ab initio calculations. The experimental spectra are found to consist of ionizing transitions populating the vibronic levels of NCCN(+), which consist of pure vibronic progressions, combination modes involving the symmetric CN stretch, the CC stretch, and even quanta of the antisymmetric CN stretch, and bending vibrations. These bands are identified with the guidance of the present ab initio calculations.


Longitudinal Tracking of Immune Responses in COVID-19 Convalescents Reveals Absence of Neutralization Activity Against Omicron and Staggered Impairment to Other SARS-CoV-2 Variants of Concern.
Evaluating long-term protection against SARS-CoV-2 variants of concern in convalescing individuals is of high clinical relevance. In this prospective study of a cohort of 46 SARS-CoV-2 patients infected with the Wuhan strain of SARS-CoV-2 we longitudinally analyzed changes in humoral and cellular immunity upon early and late convalescence. Antibody neutralization capacity was measured by surrogate virus neutralization test and cellular responses were investigated with 31-colour spectral flow cytometry. Spike-specific, isotype-switched B cells developed already during the disease phase, showed a memory phenotype and did not decrease in numbers even during late convalescence. Otherwise, no long-lasting perturbations of the immune compartment following COVID-19 clearance were observed. During convalescence anti-Spike (S1) IgG antibodies strongly decreased in all patients. We detected neutralizing antibodies against the Wuhan strain as well as the Alpha and Delta but not against the Beta, Gamma or Omicron variants for up to 7 months post COVID-19. Furthermore, correlation analysis revealed a strong association between sera anti-S1 IgG titers and their neutralization capacity against the Wuhan strain as well as Alpha and Delta. Overall, our data suggest that even 7 month after the clearance of COVID-19 many patients possess a protective layer of immunity, indicated by the persistence of Spike-specific memory B cells and by the presence of neutralizing antibodies against the Alpha and Delta variants. However, lack of neutralizing antibodies against the Beta, Gamma and Omicron variants even during the peak response is of major concern as this indicates viral evasion of the humoral immune response.


Comparative Genotoxicity of TEMPO and 3 of Its Derivatives in Mouse Lymphoma Cells.
TEMPO (2, 2, 6, 6-tetramethylphiperidine-1-oxyl) and its derivatives are stable free radical nitroxides widely used in the field of chemistry, biology, and pharmacology. TEMPO was previously found to be mutagenic and to induce micronuclei in mammalian cells. In this study, we investigated and quantified the genotoxicity of 4 structurally similar nitroxides, TEMPO and 3 of its derivatives (4-hydroxy-TEMPO, 4-oxo-TEMPO, and 4-methoxy-TEMPO), using the mouse lymphoma assay (MLA) and Comet assay in L5178Y Tk+/- cells. The results showed that all tested nitroxides were cytotoxic and mutagenic in the MLA, both in the presence and absence of S9, with metabolic activation significantly enhancing the cytotoxicity and/or mutagenicity. In addition, the 4 nitroxides caused DNA-strand breakage. The mutagenicity and DNA damaging dose-responses of the test articles were compared using the PROAST benchmark dose software package. The potency ranking of the 4 nitroxides for mutagenicity was different from the ranking of the DNA damaging effects. The mode of action analysis by a multi-endpoint DNA damage pathway assay classified all 4 nitroxides as clastogens. In addition, the majority of the induced Tk mutants showed loss of heterozygosity at the Tk and D11Mit42 loci (ie, chromosome damage <31 Mbp). These results suggest that TEMPO and its 3 derivatives are cytotoxic and mutagenic in mouse lymphoma cells through a mechanism that involves strand breakage and large alterations to DNA. The potency rankings indicate that the different TEMPO derivatives vary in their mutagenic and DNA damaging potential.


Pushing/bearing down methods for the second stage of labour.
Maternal pushing during the second stage of labour is an important and indispensable contributor to the involuntary expulsive force developed by uterine contraction. There is no consensus on an ideal strategy to facilitate these expulsive efforts and there are contradictory results about the influence on the mother and fetus. To evaluate the benefits and possible disadvantages of different kinds of techniques regarding maternal pushing/breathing during the expulsive stage of labour on maternal and fetal outcomes. We searched Cochrane Pregnancy and Childbirth's Trials Register (19 September 2016) and reference lists of retrieved studies. Randomised controlled trials (RCTs) and quasi-RCTs assessing the effects of pushing/bearing down techniques (type and/or timing) performed during the second stage of labour on maternal and neonatal outcomes. Cluster-RCTs were eligible for inclusion, but none were identified. Studies using a cross-over design and those published in abstract form only were not eligible for inclusion in this review. Two review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. Data were checked for accuracy. In this updated review, we included 21 studies in total, eight (884 women) comparing spontaneous pushing versus directed pushing, with or without epidural analgesia and 13 (2879 women) comparing delayed pushing versus immediate pushing with epidural analgesia. Our GRADE assessments of evidence ranged from moderate to very low quality; the main reasons for downgrading were study design limitations and imprecision of effect estimates. Overall, the included studies varied in their risk of bias; most were judged to be at unclear risk of bias. Comparison 1: types of pushing: spontaneous pushing versus directed pushingThere was no clear difference in the duration of the second stage of labour (mean difference (MD) 10.26 minutes; 95% confidence interval (CI) -1.12 to 21.64 minutes, six studies, 667 women, random-effects, I² = 81%) (very low-quality evidence). There was no clear difference in 3rd or 4th degree perineal laceration (risk ratio (RR) 0.87; 95% CI 0.45 to 1.66, one study, 320 women) (low-quality evidence), episiotomy (average RR 1.05; 95% CI 0.60 to 1.85, two studies, 420 women, random-effects, I² = 81%), duration of pushing (MD -9.76 minutes, 95% CI -19.54 to 0.02; two studies; 169 women; I² = 88%) (very low-quality evidence), or rate of spontaneous vaginal delivery (RR 1.01, 95% CI 0.97 to 1.05; five studies; 688 women; I² = 2%) (moderate-quality evidence). For primary neonatal outcomes such as five-minute Apgar score less than seven, there was no clear difference between groups (RR 0.35; 95% CI 0.01 to 8.43, one study, 320 infants) (very low-quality evidence), and the number of admissions to neonatal intensive care (RR 1.08; 95% CI 0.30 to 3.79, two studies, 393 infants) (very low-quality evidence) also showed no clear difference between spontaneous and directed pushing. No data were available on hypoxic ischaemic encephalopathy. Comparison 2: timing of pushing: delayed pushing versus immediate pushing (all women with epidural)For the primary maternal outcomes, delayed pushing was associated with an increase of 56 minutes in the duration of the second stage of labour (MD 56.40, 95% CI 42.05 to 70.76; 11 studies; 3049 women; I² = 91%) (very low-quality evidence), but no clear difference in third or 4th degree perineal laceration (RR 0.94; 95% CI 0.78 to 1.14, seven studies. 2775 women) (moderate-quality evidence) or episiotomy (RR 0.95; 95% CI 0.87 to 1.04, five studies, 2320 women). Delayed pushing was also associated with a 19-minute decrease in the duration of pushing (MD -19.05, 95% CI -32.27 to -5.83; 11 studies; 2932 women; I² = 95%) (very low-quality evidence) and an increase in spontaneous vaginal delivery (RR 1.07; 95% CI 1.02 to 1.11, 12 studies, 3114 women) (moderate-quality evidence).For the primary neonatal outcomes, there was no clear difference between groups in admission to neonatal intensive care (RR 0.98; 95% CI 0.67 to 1.41, three studies, n = 2197) (low-quality evidence) and five-minute Apgar score less than seven (RR 0.15; 95% CI 0.01 to 3.00; three studies; 413 infants) (very low-quality evidence). There were no data on hypoxic ischaemic encephalopathy. Delayed pushing was associated with a greater incidence of low umbilical cord blood pH (RR 2.24; 95% CI 1.37 to 3.68, 4 studies, 2145 infants) and increased the cost of intrapartum care by CDN$ 68.22 (MD 68.22, 95% CI 55.37, 81.07, one study, 1862 women). This updated review is based on 21 included studies of moderate to very low quality of evidence (with evidence mainly downgraded due to study design limitations and imprecision of effect estimates).Timing of pushing with epidural is consistent in that delayed pushing leads to a shortening of the actual time pushing and increase of spontaneous vaginal delivery at the expense of an overall longer duration of the second stage of labour and an increased risk of a low umbilical cord pH (based only on one study). Nevertheless, there was no clear difference in serious perineal laceration and episiotomy, and in other neonatal outcomes (admission to neonatal intensive care, five-minute Apgar score less than seven and delivery room resuscitation) between delayed and immediate pushing.Therefore, for the type of pushing, with or without epidural, there is no conclusive evidence to support or refute any specific style as part of routine clinical practice, and in the absence of strong evidence supporting a specific method or timing of pushing, the woman's preference and comfort and clinical context should guide decisions.Further properly well-designed RCTs, addressing clinically important maternal and neonatal outcomes are required to add evidence-based information to the current knowledge. Such trials will provide more complete data to be incorporated into a future update of this review.


A Novel Fasciocutaneous Flap Design for Reconstructions in Scarred Tissue: A Case Report.
This article aims to introduce a technically easy and reliable flap design for the coverage of soft tissue defects in areas where traditional flap options are limited by trauma or scarring. We applied the boomerang design in cases with defects around the knee and also extrapolated it to other regions like the wrist and sacrum. Patients with soft tissue defects in regions with scarred tissues or limited flap reconstructive options were recruited. The procedures resulted in uneventful recovery and excellent cosmetic outcomes for the patients. The authors of this article recommend the usage of this uncomplicated flap design in areas with otherwise limited flap options due to restricted vascularity or surrounding scar tissue.


Enhanced Diffusion of Passive Tracers in Active Enzyme Solutions.
Colloidal suspensions containing microscopic swimmers have been the focus of recent studies aimed at understanding the principles of energy transfer in fluidic media at low Reynolds number conditions. Going down in scale, active enzymes have been shown to be force-generating, nonequilibrium systems, thus offering opportunity to examine energy transfer at the ultralow Reynolds number regime. By monitoring the change of diffusion of inert tracers dispersed in active enzyme solutions, we demonstrate that the nature of energy transfer in these systems is similar to that reported for larger microscopic active systems, despite the large differences in scale, modes of energy transduction, and propulsion. Additionally, even an enzyme that catalyzes an endothermic reaction behaves analogously, suggesting that heat generation is not the primary factor for the observed enhanced tracer diffusion. Our results provide new insights into the mechanism of energy transfer at the molecular level.


Evaluation of tenofovir disoproxil fumarate loaded silver nanoparticle on testicular morphology in experimental type-2 diabetic rats.
Reproductive derangement and metabolic disorders in human immunodeficiency virus (HIV) infected persons require a nanoparticle delivery system to convey antiretroviral drugs to the anatomical sanctuary such as testis. This study investigated the effects of tenofovir disoproxil fumarate (TDF) loaded silver nanoparticles (AgNPs) on the testicular oxidative stress, inflammatory cytokines and histology in male diabetic rats. Thirty-six Sprague-Dawley rats weighing 230 ± 20 g were randomly divided into diabetic and non-diabetic groups (n = 18). Diabetes was induced using the fructose-streptozotocin (Frt-STZ) rat model. Both groups were further divided into three (n = 6) and administered distilled water, TDF, or TDF-AgNP. Results obtained with the TDF-AgNP administration showed a significant increase (p < .05) in the reduced glutathione and catalase levels. Tumour necrosis factor-alpha and interleukin 6 were reduced in diabetic rats administered TDF-AgNP. More so, administration of TDF-AgNP to diabetic rats improved testicular histoarchitecture in diabetic rats. In addition, diabetic rats administered TDF-AgNP showed a significant reduction (p < .05) in blood glucose levels. TDF-AgNP to diabetic rats enhanced testicular antioxidant enzyme, reduced testicular inflammation, and alleviated structural derangements in the testis. Thus, the application of AgNP to deliver TDF may alleviate testicular toxicity and subsequently cater for neglected reproductive dysfunction during the management of HIV infection.


[Generalized tetanus complicating a traditional medicine applied for snakebite].
In many of Africa's rural areas, snakebite victims often resort to traditional healers for first line treatment. This may be source of infectious complications. We report a case of generalized tetanus which occured after 15 days in a 13-years old boy who had applied a traditional, plant-based concoction on a snake bite. He presented with trismus, generalized contractures and fever extended musculo-aponevrotic necrosis of the right upper limb, without loss of consciousness. The only accompanying biological sign was an increased leukocyte count (11,200/mm3) with a predominance of neutrophils (84%). Platelets count, creatinin and AST/ALT titers and haemostasis were all normal, as was the radiogram of the right hand. The clinical outcome was favourable after 3 weeks hopital care (antibiotic, muscle relaxants, antitetanus serotherapy and local wounds care). This clinical observation shows that traditional care for snake bite wounds can be an entry point for tetanus. Appropriate treatment of snake bites in a hospital setting is of the utmost importance, in addition to vaccination against tetanus, in order to reduce the incidence of tetanus in African countries.