Current trends in chemotherapy for metastatic nonseminomatous testicular germ cell tumors.
With the introduction of cisplatin-based chemotherapy, metastatic testicular cancer represents a model for a highly curable malignant disease. Approximately 70-80% of patients achieve a durable remission following chemotherapy +/- secondary surgery of residual tumors. With the development of prognostic classifications based on clinically available parameters, the aims of chemotherapy have been twofold: on the one hand, the reduction of toxicity in patients with 'low-risk' metastatic disease without a concomitant reduction in treatment efficacy and, on the other hand, the improvement of treatment results in patients with 'poor-prognosis' criteria who achieve a long-term cure rate of less than 50% with standard chemotherapy regimens. Despite a number of large randomized studies attempting either to avoid the toxicity of bleomycin or to reduce cisplatin-associated side-effects through the substitution with carboplatin, the combination of cisplatin, etoposide and bleomycin (PEB) given at 3-week intervals still remains the standard treatment for metastatic disease. The role of high-dose chemotherapy with autologous stem cell support is currently being investigated in order to improve the outcome of patients with relapse after previous chemotherapy and of patients initially exhibiting advanced metastatic disease. For patients with relapsed disease receiving high-dose chemotherapy, a prognostic score has recently been developed: cisplatin-refractory disease, beta human gonadotropin values > 1,000 U/l or primary mediastinal germ cell tumors are factors characterizing patients which will profit less from high-dose chemotherapy treatment than patients with chemosensitive disease at relapse. Standard dose salvage regimens only result in a 20% long-term survival rate. In contrast, high-dose salvage chemotherapy may yield a cure rate of approximately 40%. However, the only randomized study comparing high-dose versus conventional-dose therapy in patients with relapsed disease is still ongoing. The investigation of dose-intensive approaches as first-line treatment is currently being studied by several institutions. Despite preliminary favorable results, this approach still cannot be considered standard treatment. A randomized study comparing high-dose chemotherapy with 4 cycles of standard PEB was initiated in the USA in 1996. The evaluation of new drugs in testicular cancer patients with absolute cisplatin-refractory disease has demonstrated that paclitaxel is one of the few agents with antitumor activity in these patients. Paclitaxel has therefore been included in combination regimens--such as cisplatin, ifosfamide and paclitaxel--for the treatment of patients with first and second relapse of testicular cancer. These combinations are used as induction therapy prior to high-dose salvage treatment. Due to the large group of patients with metastatic disease being cured nowadays, the long-term side effects of treatment have become even more important. One of the major risk factors for the development of late toxicities such as oto-, neuro-, nephro-, gonadal and cardiovascular toxicity is the cumulative dose of cisplatin applied during therapy. The development of new treatment strategies, such as the use of adjuvant chemotherapy for stage I disease, the widespread application of high-dose chemotherapy with peripheral stem cell rescue and the use of new cytotoxic agents, makes the evaluation of the late effects of treatment for testicular cancer within controlled clinical trials mandatory.


Connexin 26 (GJB2) gene mutations linked with autosomal recessive non-syndromic sensor neural hearing loss in the Iraqi population.
Deafness is a total or partial hearing loss that may appear at any age and with different degrees of severity. Approximately 50% of hearing loss have a genetic origin, and among them, non-syndromic sensorineural deafness represents about 70% of the cases. From them, 80% correspond to autosomal recessive inheritance deafness. Autosomal recessive deafness was not studied enough at the molecular level in Iraq. This study aimed to verify the frequency of three GJB2 mutations in non-syndromic sensorineural deafness in the Iraqi population. The current case-control study was conducted from January 2018 to January 2020. The study included 95 deafness patients (55 males and 40 females) and 110 healthy control group. Age and sex were matched between the two groups. In order to detect c.35delG, 235delC, and 167delT mutations in the GJB2 gene, we employed the PCR-RFLP technique. The c.35delG was the main frequent mutation encountered with the GJB2 gene among patients with autosomal recessive non-syndromic sensorineural hearing loss. Among them, 35 (36.8%) were homozygous, 40 (42.1%) were heterozygous, and 20 (21.1%) were wild genotypes. The second-degree mutation in the GJB2 gene was c.235delC mutation, which from the 95 deaf patients, there were 20 (21.1%) with homozygous, 33 (34.7%) heterozygous, and 42 (44.2%) wild genotypes. None of the 95 deaf patients showed the c.167delT mutation, and no mutations appeared in the control group. Our data concluded that the GJB2 c.35delG and c.235delC gene mutations were the main cause of autosomal recessive non-syndromic sensorineural hearing loss in the Iraqi deaf population.


Inhibition of adherence of Candida albicans by conventional and experimental antifungal drugs.
We tested the effects of antifungal drugs on adherence of Candida albicans in vitro. Significant reduction of adherence occurred after 2 h incubation with amphotericin B, nystatin, miconazole, econazole, ketoconazole, chlorohexidine and ICI 195,739. Significant inhibition of candida adherence by 5-fluorocytosine and amorolfin required 18 h incubation. Combinations of amphotericin B with 5-fluorocytosine, miconazole, ICI 195,739 and amorolfin resulted in synergistic inhibition of adherence. Adherence is an important pathogenic mechanism in candida infections and interference with this process may represent a major component of the mode of action of antifungal drugs.


Pharmacokinetics of intravenous clindamycin phosphate in captive Bennett's wallabies (Macropus rufogriseus).
This study was designed to investigate the pharmacokinetics of clindamycin, a lincosamide antibiotic, in Bennett's wallabies. The pharmacokinetic properties of a single intravenous (IV) dose of clindamycin were determined in six wallabies. A single 20-min IV infusion of 20 mg/kg of clindamycin was administered, followed by blood collection prior to, and up to 12 hr after clindamycin administration. Plasma clindamycin concentrations were determined by high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection. Pharmacokinetic variables were calculated using a two-compartment model with first order elimination which best fit the data. The mean volume of distribution at steady-state, distribution half-life, and elimination half-life were 898.25 ml/kg, 0.16 hr, 1.79 hr, respectively. No adverse effects were noted after IV administration.


Chlorabietols A-C, Phloroglucinol-Diterpene Adducts from the Chloranthaceae Plant Chloranthus oldhamii.
Three unprecedented phloroglucinol-diterpene adducts, chlorabietols A-C (1-3), were isolated from the roots of the rare Chloranthaceae plant Chloranthus oldhamii. They represent a new class of compounds, featuring an abietane-type diterpenoid coupled with different alkenyl phloroglucinol units by forming a 2,3-dihydrofuran ring. Their structures were elucidated by detailed spectroscopic analysis, molecular modeling studies, and electronic circular dichroism calculations. Compounds 1-3 showed inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 12.6, 5.3, and 4.9 μM, respectively.


Acute and subacute hemodynamic effects of enalaprilat, milrinone and combination therapy in rats with chronic left ventricular dysfunction.
A model of congestive heart failure (CHF) was produced in rats approximately 76 days following surgical occlusion of the left coronary artery. In rats with healed myocardial infarction (MI size = 45% LV), hemodynamic variables were predictably elevated (LVEDP greater than 20 mm Hg) or depressed LV dP/dtmax (5200 mm Hg/sec). The hemodynamic response (MAP, HR, LVEDP, and dP/dtmax) to intravenous infusion of Mil (54 to 347 micrograms/kg) was measured on two occasions, separated by a 7-12 day period of oral treatment (2 mg/kg/day). Enalaprilat was tested in a similar design with the infusion phase (70 micrograms/kg, total dose) separated by oral enalapril (Enal), 1 mg/kg/day. The hemodynamic response to Mil was also examined in rats treated with the ACE inhibitor. At low doses, Mil modestly elevated HR (+17 beats/min) and dose-dependently increased (P less than 0.05) LV contractility by approximately 25%. Higher doses of Mil reduced preload (LVEDP) and afterload (MAP). Oral Mil produced little hemodynamic improvement except modest elevation (+9%) in LV contractility. There was no evidence of tachyphylaxis to i.v. Mil. In contrast, enalaprilat reduced MAP and preload without altering HR or contractility, effects observed after oral treatment. In the presence of the ACE inhibitor, Mil's hemodynamic actions were not enhanced. These experiments demonstrate that ACE inhibition improves ventricular performance by reducing preload and afterload. In this model, Mil improves performance by a direct inotropic mechanism as well as a reduction in afterload.


Prophylaxis with teicoplanin and cefuroxime reduces the rate of prosthetic joint infection after primary arthroplasty.
The aim of this study was to compare the prosthetic joint infection (PJI) rate after total joint arthroplasty in two consecutive periods of treatment with different antibiotic prophylaxes: cefuroxime versus cefuroxime plus teicoplanin. We retrospectively reviewed 1,896 patients who underwent total hip arthroplasty or total knee arthroplasty between March 2010 and February 2013. From March 2010 to August 2011, patients received 1.5 g of cefuroxime during induction of anesthesia and another 1.5 g 2 h later (the C group). From September 2011, 800 mg of teicoplanin was added to cefuroxime (the CT group). Throughout the period studied, there were no variations in pre- or postoperative protocols. Univariate and multivariate analyses were performed to evaluate independent predictors of PJI. There were 995 (55.7%) patients in the C group and 791 (44.3%) in the CT group. Patients in the CT group had a significantly lower PJI rate than patients in the C group (1.26% versus 3.51%, P=0.002). There were no infections due to Staphylococcus aureus in the CT group (0% versus 1.6% in the C group, P<0.001). A stepwise forward Cox regression model identified male sex (hazard ratio [HR], 3.85; 95% confidence interval [CI], 2.09 to 7.18), a body mass index of ≥35 kg/m2 (HR, 2.93; 95% CI, 1.37 to 6.27), the presence of lung disease (HR, 2.46; 95% CI, 1.17 to 5.15), and red blood cell transfusion (HR, 3.70; 95% CI, 1.89 to 7.23) to be independent variables associated with a higher risk of PJI. The addition of teicoplanin was associated with a lower risk of infection (HR, 0.35; 95% CI, 0.17 to 0.74). In conclusion, the addition of teicoplanin to cefuroxime during primary arthroplasty was associated with a significant reduction in the global PJI rate due to a reduction of infections caused by Gram-positive bacteria.


Interplay between stochastic and deterministic processes in the maintenance of alternative community states in Verrucomicrobia-dominated shallow lakes.
We analyzed the interplay between neutral and deterministic processes in maintaining contrasting alternative bacterioplankton communities through time in highly productive shallow lakes and evaluated the relevance of these processes when a regime shift from a clear to a turbid state occurred. We observed that local assembly is ruled primary deterministically, via local habitat filtering, with a secondary role of stochastic processes. We also found a hierarchy in the environmental sorting: while an unusual Verrucomicrobia dominance characterizes the three systems, local conditions limit within-bacterial community membership to closely phylogenetically related and ecologically similar taxa. These results indicate that bacterial abilities to establish in these lakes are strongly determined by their traits, and point toward special physiological adaptations to persist when these systems undergo a regime shift. Altogether, these results hint to a divergence in function among these alternative communities, mediated by major shifts in bacterial community trait structure, particularly regarding carbon use.


Neurosurgical training programme in selected European countries: from the young neurosurgeons' point of view.
In this paper we discuss the Neurosurgical Training Programme (NTP) in some European countries. Although there is no official data on how many neurosurgeons are certified in Europe, our calculation shows that this number is somewhat lower than in the United States of America and even 3 times lower than in Japan (per 100.000 population). It is also evident that there is no consensus in the Programme duration or in the official NTP content, despite the recommendations of the EANS (The European Association of Neurosurgical Societies). Trainees from outside the European Union (EU) are under-represented in the EANS training courses. We believe that in the eastern part of Europe there is the most space for improvement in neurosurgical training. Solving of all these problems requires first and foremost their recognition and consideration - then devising a solution. The purpose of this paper is to compare and contrast several NTP's in Europe in order to promote a more coherent medical education. Some remarks and suggestions from the perspective of young neurosurgeons are given.


The effect of sodium based hypo-osmolality on arterial smooth muscle reactivity in vitro.
The study tested the hypothesis that the reduced [Na+]e and hypo-osmolality of normal pregnancy are causally linked to the attenuation of vascular smooth muscle reactivity in vitro. Aortic rings from nonpregnant female rats were incubated in physiological medium containing 114 mM NaCl/l and the contractile responses to phenylephrine, KCl and CaCl2 as well as the relaxations to acetylcholine and KCl were compared with those of rings incubated in normal medium containing 119 mM NaCl/l. There was no solute substituted for the lowered [Na+]. Experiments with phenylephrine were repeated using de-endothelialized rings and intact rings pretreated with indomethacin. Contractile responses of intact rings (n = 11) in hypo-osmolar solution to phenylephrine were significantly (P < 0.001) lower than of those in normal medium (n = 11). Responses were partially restored by endothelial denudation but not in the presence of indomethacin. Relaxations to acetylcholine (n = 7 for hypo-osmolar; n = 6 for normal solution) and KCl (n = 7 for each of hypo- and normal osmolar) were significantly enhanced (P < 0.05) in rings incubated in hypo-osmolar solution. There was no significant difference between the responses of the rings to KCl, and CaCl2 in either solution. These effects are similar to some of those previously described for vascular smooth muscle in normal pregnancy suggesting that the reduced [Na+]e and hypo-osmolarity of normal pregnancy may be contributing to the diminished vascular reactivity.


Ulipristal acetate before high complexity endoscopic (hysteroscopic, laparoscopic) myomectomy - a mini-review.
Uterine myomas (fibromas, leiomyomas) are the most common tumours in women, and their clinical signs and symptoms are presented by 25-40% of patients with these benign tumours. According to current guidelines, the armamentarium for myoma management consists of: medical therapy (GnRH, SPRMs), non-surgical alternatives including uterine artery embolisation (UAE), vaginal temporary occlusion of uterine arteries using clamp-like device or MRgFUS technique, and surgical treatment (including minimally invasive techniques). In cases of submucous myomas STEPW classification correlates very well with the risk of incomplete hysteroscopic myomectomies. According to limited literature data, ulipristal acetate as a pre-treatment seems to be very prudent in high complexity hysteroscopic myomectomy (STEPW II, score 5-6). In patients with large uterine myomas (FIGO type 3, 4, 5) undergoing laparoscopic myomectomy, three-month pre-treatment with ulipristal acetate before laparoscopy is feasible and can be recommended because of shorter time of surgery, lower intraoperative blood loss, lower haemoglobin drop, and low postoperative blood transfusion rate.


Cost-utility of ferric carboxymaltose (Ferinject®) for iron-deficiency anemia patients with chronic heart failure in South Korea.
Iron-deficiency anemia (IDA) is prevalent in patients with advanced chronic heart failure (CHF). It affects the patients' overall physical condition and is suggested as a strong outcome predictor in CHF. Recent clinical trials suggested that intravenous iron supplementation improves CHF functional status and quality of life. The aim of this study was to assess the cost-effectiveness of ferric carboxymaltose(FCM) in CHF patients with IDA. Ferric carboxymaltose, an intravenous iron preparation, was compared with placebo. The target population comprised CHF patients with IDA in hospital and outpatient care settings. We conducted this study from the Korean healthcare payers' perspective with a time horizon of 24 weeks. One clinical trial provided the clinical outcomes of ferric carboxymaltose therapy. The improvement rates of the New York Heart Association (NYHA) functional class in the placebo and ferric carboxymaltose groups were used to estimate effectiveness in the base-case model. We also conducted a scenario 2 analysis using quality of life investigated in the clinical trial. A panel survey was conducted to obtain the ratio of healthcare resource use based on NYHA class in Korea. Cost-effectiveness was expressed as incremental cost (US dollars) per quality-adjusted life-year (QALY) gained. In the base-case analysis, the incremental cost-effectiveness ratio (ICER) of ferric carboxymaltose compared with placebo was $22,192 (₩25,010,451) per QALY gained. The sensitivity analysis showed robust results, with the ICERs of ferric carboxymaltose ranging from $5,156 to $29,796 per QALY gained. In the scenario 2 analysis, ICER decreased to $12,598 (₩14,198,501) per QALY gained. Iron repletion with ferric carboxymaltose for IDA in CHF patients was cost-effective compared with placebo.


FLT3 tyrosine kinase inhibitors.
The receptor tyrosine kinase FLT3 is an important regulatory molecule in hematopoiesis and is expressed on the blasts in most cases of acute leukemia. Activating mutations of this receptor are present in roughly 30% of acute myeloid leukemia (AML) patients and are associated with a distinctly worse clinical outcome. Efforts to target this mutation and improve out-comes in this subgroup of AML patients have led to the investigation of several novel small-molecule FLT3 tyrosine kinase inhibitors. These compounds derive from a wide variety of chemical classes and differ significantly, both in their potency and in their selectivity. In this review, we discuss the results of preclinical, clinical, and correlative laboratory studies of FLT3 inhibitors in demonstrating how this field represents a truly translational enterprise with multiple ongoing interactions between the laboratory and the clinic.


Acutely developing, spurious anaemia without actual blood loss. A paradigmatic case report.
We describe the case of a 55-year old women admitted at night to the emergency department (ED), complaining for acute abdominal pain lasting for nearly 5 hours. A first blood testing, performed immediately after admission, revealed mild anaemia. A second blood sample, drawn two hours after admission, revealed a considerable decrease of haemoglobin, haematocrit, total white blood cell and platelet counts (between 10-15% reduction). Abdominal ultrasonography was normal and the patient had no signs or symptoms of internal or external haemorrhage. Pre-analytical and analytical errors were accurately excluded. No infusion therapy was administered. After thoughtful discussing the sequence of events, it was ascertained that the first set of blood samples was drawn with the patient in seated position, immediately after ED admission (i.e., approximately 1 min passed from standing to seated position before venipuncture), whereas the second set of blood samples was drawn with the patient lying for two hours in supine position. This case report highlights the importance of standardizing patient position before venous blood collection, along with the crucial role played by cooperation and communication between laboratory and clinical wards for identifying and troubleshooting potential causes of spurious results of in vitro diagnostic testing.


Cr(i)Cl as well as Cr+ are stabilised between two cyclic alkyl amino carbenes.
Cr(i)Cl is a very unstable species. The present work describes the stabilisation of Cr(i)Cl in the low coordinate environment of cyclic alkyl(amino) carbene ligands and its synthetic application to yield an unprecedented cationic complex with a two coordinate Cr(i). One electron reduction of (cAAC)2CrCl2 (1) with equivalent amount of KC8 results in the formation of (cAAC)2CrCl (2), with a distorted trigonal planar configuration at the metal centre. SQUID, EPR and theoretical studies reveal a Cr(i) centre with S = 5/2 spin ground state for 2. It represents the first example of a mononuclear Cr complex showing slow relaxation of magnetisation under an applied magnetic field. The chlorine atom in 2 is expected to be prone to further reactions with appropriate reagents. This qualifies 2 as a promising precursor for the preparation of various interesting complexes with Cr(i) in a low coordinate environment. The first example of this metathesis reaction is observed when 2 is treated with Na[B(C6H3(CF3)2)4] resulting in [(cAAC)2Cr]+[B(C6H3(CF3)2)4]-, a linear cationic complex with two coordinate Cr(i) and an S = 5/2 spin ground state.


Caveats for the Use of the Active Problem List as Ground Truth for Decision Support.
Diagnoses recorded on the problem list are increasingly being used for decision support applications. To obtain insight in the adequacy of the clinical user interface to capture what the clinician has in mind, and to reconstruct the clinical reality of the patient, we analyzed in the database of an EHR system the transactions that resulted from managing the problem list. Our findings indicate (1) that caution is required when using the evolution of the problem list for determining comorbidity or ongoing disease, and (2) that similarities or differences in problem list annotation sequences do not always correspond with similarities resp. differences in disease courses. It is to be investigated whether automatically identifiable subsets of problem list evolution patterns exist from which ground truth reliably can be inferred or whether clinicians need more education in how problem list user interfaces should be used to avoid erroneous interpretations by clinical decision support applications.


History and current status of divorce in the United States.
This article explores the remarkable shift in marriage and divorce practices that has occurred in the last third of this century in the United States. Initially, information is presented on trends in divorce and remarriage; commonalities and differences between family patterns in the United States and in other industrialized nations are discussed. The author then identifies some of the factors that have transformed marriage practices in the United States and describes how changes in these practices have altered the family experiences of children. Finally, the author suggests trends in family patterns that might occur in the near future and discusses various policy initiatives and how they may influence the future of the family.


Ischemia/reperfusion-induced increase in the hepatic level of prostacyclin is mainly mediated by activation of capsaicin-sensitive sensory neurons in rats.
Capsaicin-sensitive sensory neurons are nociceptive neurons that release calcitonin gene-related peptide (CGRP) on activation by various noxious stimuli. CGRP has been shown to increase the endothelial production of prostacyclin, which reduces ischemia/reperfusion (I/R)-induced liver injury. Therefore, if the sensory neurons can be activated by the pathologic process of hepatic I/R, they might help ameliorate I/R-induced liver injury by promoting the endothelial production of prostacyclin, also known as prostaglandin I(2). In this study, we examined these possibilities using a rat model of I/R-induced liver injury. Male Wistar rats were subjected to 60-minute hepatic ischemia and subsequent reperfusion. Hepatic levels of 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), a stable metabolite of prostacyclin, were significantly increased after hepatic I/R, peaking 1 hour after reperfusion. Administration of capsaicin and CGRP significantly enhanced I/R-induced increases in hepatic levels of 6-keto-PGF(1alpha), increased hepatic-tissue blood flow after reperfusion, and inhibited the I/R-induced increase in tissue levels of both tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase. Capsazepine, a vanilloid receptor antagonist; CGRP(8-37), a CGRP-receptor antagonist; l-nitro-arginine-methyl-ester (L-NAME), a nonselective inhibitor of nitric oxide (NO) synthase (NOS); and indomethacin, a nonselective inhibitor of cyclooxygenase, inhibited the I/R-induced increases in hepatic tissue levels of 6-keto-PGF(1alpha) and decreased hepatic-tissue blood flow after reperfusion. These compounds significantly enhanced the I/R-induced increases in hepatic tissue levels of both TNF-alpha and myeloperoxidase. Although I/R-induced liver injury was significantly reduced by capsaicin and CGRP, it was exacerbated by capsazepine, CGRP(8-37), L-NAME, and indomethacin. Administration of aminoguanidine, a selective inhibitor of the inducible form of NOS, and NS-398, a selective inhibitor of cyclooxygenase-2, demonstrated no effects on the liver injury or the hepatic levels of 6-keto-PGF(1alpha). These findings strongly suggest that the activation of the sensory neurons helps ameliorate I/R-induced liver injury both by increasing hepatic-tissue blood flow and by limiting inflammatory response through the enhancement of endothelial production of prostacyclin. In the sensory neuron-mediated enhancement of endothelial production of prostacyclin, CGRP-induced activation of both endothelial NOS and cyclooxygenase-1 may be critically involved.


A human in vitro neuronal model for studying homeostatic plasticity at the network level.
Mechanisms that underlie homeostatic plasticity have been extensively investigated at single-cell levels in animal models, but are less well understood at the network level. Here, we used microelectrode arrays to characterize neuronal networks following induction of homeostatic plasticity in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons co-cultured with rat astrocytes. Chronic suppression of neuronal activity through tetrodotoxin (TTX) elicited a time-dependent network re-arrangement. Increased expression of AMPA receptors and the elongation of axon initial segments were associated with increased network excitability following TTX treatment. Transcriptomic profiling of TTX-treated neurons revealed up-regulated genes related to extracellular matrix organization, while down-regulated genes related to cell communication; also astrocytic gene expression was found altered. Overall, our study shows that hiPSC-derived neuronal networks provide a reliable in vitro platform to measure and characterize homeostatic plasticity at network and single-cell levels; this platform can be extended to investigate altered homeostatic plasticity in brain disorders.


The XPC-HR23B complex displays high affinity and specificity for damaged DNA in a true-equilibrium fluorescence assay.
The XPC-HR23B complex is a prime candidate for the initial damage recognition step during global genome nucleotide excision repair. A specific interaction between the XPC-HR23B complex and various types of damaged DNA substrates has been demonstrated in recent work by electrophoretic mobility shift assays or immunoprecipitation. Although these studies allowed the estimation of relative binding affinities for the different types of lesions, the presence of large amounts of competitor DNA or the need for glutaraldehyde fixation prevented the quantification of equilibrium constants. We have performed a quantitative study on the binding of XPC to damaged DNA using fluorescence anisotropy measurements. The XPC-HR23B complex binds with high affinity (K(D) approximately 1-3 nM) to fluorescent 36 bp DNA fragments containing a single cisplatin 1,3-intrastrand adduct or a six-nucleotide mispaired region. From stoichiometric titration experiments, it is concluded that approximately 70% of the XPC-HR23B preparation is active in DNA binding. Binding experiments employing fluorescent probes with a single defined photoproduct reveal a 30-fold preference of XPC for 6,4-photoproducts as compared to a cyclobutane dimer. Competition experiments with undamaged and damaged plasmid DNA indicate that the XPC-HR23B complex discriminates between damaged and undamaged sites with high specificity. The specificity factor is between 100 and 3000, depending on the number of nonspecific sites considered in the calculations. Upon addition of XPA to the XPC binding reaction mixtures, it was not possible to detect cooperative ternary complex formation on the platinated 36 bp probe.


[The role of environmental factors in managing labour stress].
Emotional, cognitive and behavioural aspects of birth and labour stress are strongly associated with the underlying physiological processes. To study the factors of physical security and social support, the administration of synthetic oxytocin, and how they relate to perceived stress during childbirth. Women's experienced physical security, social support and oxytocin administration was measured with targeted questions, and their perceived stress with the short and modified version of the Perceived Stress Scale. A strong negative association was found between perceived stress and physical and social security. The group of women experiencing low physical and social security perceived significantly higher stress, while those given synthetic oxytocin perceived higher stress, and lower physical and social security. Since physiological, psychological processes and behaviours are strongly intertwined, the support of natural physiological birth without interventions is recommended, which considers not only short-term but long-term health consequences for mother and child. The contribution of calming physical surroundings, minimal interventions and empowering support of caregivers to safe and satisfying birth is demonstrated in a model. Orv Hetil. 2017; 158(29): 1149-1156.


Isolated spinal cord compression syndrome revealing delayed extensive superficial siderosis of the central nervous system secondary to cervical root avulsion.
Cervical root avulsion secondary to traumatic plexus injury is a rare etiology of superficial siderosis (SS) of the central nervous system (CNS). We describe the case of an isolated progressive compressive myelopathy revealing this complication and discuss the pathogenesis of such a presentation, its clinical and imaging peculiarities with a literature review. We report on the case of a 48-year-old man with history of left brachial plexus injury at the age of 2 years. Since the age of 38 years, he had presented with a progressive paraplegia, bladder and erectile dysfunction, neuropathic pain and sensory level. The diagnosis was made by spinal cord and brain magnetic resonance follow-up imaging revealing hypointensity T2-weighted gradient echo linear dark rim around the entire neuraxis and cervical dural pseudomeningoceles. These MRI findings were suggestive of extensive hemosiderin deposition consolidating the diagnosis of SS of CNS. Our case report illustrates diagnosis difficulties in unusual or paucisymptomatic presentations of SS. A history of brachial plexus trauma with nerve root avulsion should prompt gradient-echo T2-weighted imaging to bring out such a complication. Superficial siderosis of the CNS should be included in the panel of differential diagnosis of the parethospastic syndromes and compressive myelopathy.


Objective evaluation of shoulder pain by measuring skin impedance.
The subjective nature of pain has made its objective evaluation rather difficult. Recently, skin impedance was reported to reflect pain. The purpose of this study was to determine the usefulness of measuring skin impedance in evaluating shoulder pain. Fifty-three patients with shoulder pain were examined. Skin impedance was measured by a skin impedance meter in three different conditions and was compared with the visual analog scale recorded at the same time.


Cystine-glutamate transporter SLC7A11 mediates resistance to geldanamycin but not to 17-(allylamino)-17-demethoxygeldanamycin.
The cystine-glutamate transporter SLC7A11 has been implicated in chemoresistance, by supplying cystine to the cell for glutathione maintenance. In the NCI-60 cell panel, SLC7A11 expression shows negative correlation with growth inhibitory potency of geldanamycin but not with its analog 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), which differs in the C-17 substituent in that the the methoxy moiety of geldanamycin is replaced by an amino group. Structure and potency analysis classified 18 geldanamycin analogs into two subgroups, "17-O/H" (C-17 methoxy or unsubstituted) and "17-N" (C-17 amino), showing distinct SLC7A11 correlation. We used three 17-O/H analogs and four 17-N analogs to test the role of the 17-substituents in susceptibility to SLC7A11-mediated resistance. In A549 cells, which are resistant to geldanamycin and strongly express SLC7A11, inhibition of SLC7A11 by (S)-4-carboxyphenylglycine or small interfering RNA increased sensitivity to 17-O/H, but had no effect on 17-N analogs. Ectopic expression of SLC7A11 in HepG2 cells, which are sensitive to geldanamycin and express low SLC7A11, confers resistance to geldanamycin, but not to 17-AAG. Antioxidant N-acetylcysteine, a precursor for glutathione synthesis, completely suppressed cytotoxic effects of 17-O/H but had no effect on 17-N analogs, whereas the prooxidant ascorbic acid had the opposite effect. Compared with 17-AAG, geldanamycin led to significantly more intracellular reactive oxygen species (ROS) production, which was quenched by addition of N-acetylcysteine. We conclude that SLC7A11 confers resistance selectively to 17-O/H (e.g., geldanamycin) but not to 17-N (e.g., 17-AAG) analogs partly as a result of differential dependence on ROS for cytotoxicity. Distinct mechanisms could significantly affect antitumor response and organ toxicity of these compounds in vivo.


Acute fatty liver of pregnancy: analysis of five consecutive cases from a tertiary centre.
Acute fatty liver of pregnancy is a rare cause of jaundice and liver failure associated with high maternal and fetal mortality. We analysed five consecutive cases of acute fatty liver of pregnancy, along with the associated morbidity, mortality and complications. Between January 1999 and January 2008, a total of 68,524 deliveries were assisted at the Obstetrics and Gynaecology Department of the Hospital Universitario Materno-Infantil de Canarias (Canaries University Hospital Maternity Ward); among them, five cases of acute fatty liver of pregnancy were identified.


Accessibility, availability and utilisation of malaria interventions among women of reproductive age in Kilosa district in central Tanzania.
Universal access to and utilization of malaria prevention measures is defined as every person at malaria risk sleeping under a quality insecticide-treated mosquito net (ITN) and every pregnant woman at risk receiving at least two doses of sulfadoxine-pyrimethamine (SP). This study aimed to determine factors affecting accessibility, availability and utilisation of malaria interventions among women of reproductive age in Kilosa district in central Tanzania. Women of reproductive age with children <5 years old or those who had been pregnant during the past 5 years were included in the study. A structured questionnaire was used to seek information on malaria knowledge, accessibility and utilization of malaria interventions during pregnancy. A total of 297 women (mean age=29±6.8 years) were involved. Seventy percent of the women had attained primary school education. About a quarter of women had two children of <5 years while over 58% had ≥3 children. Most (71.4%) women had medium general knowledge on malaria while only eight percent of them had good knowledge on malaria in pregnancy. A significant proportion of women were not aware of the reasons for taking SP during pregnancy (35%), timing for SP (18%), and the effect of malaria on pregnancy (45.8%). Timing for first dose of SP for intermittent preventive treatment in pregnancy (IPTp) was 1-3 months (28.4%) and 4-6 months (36.8%). Some 78.1% were provided with SP under supervision of the health provider. Knowledge on malaria in pregnancy had a significant association with levels of education (p=0.024). Ninety-eight percent had an ITN, mostly (87.1%) received free from the government. All women attended the ANC during their last pregnancy. The coverage of IPT1 was 53.5% and IPTp2 was 41.1%. The proportion of women making more ANC visits decreased with increasing parity. This study showed that the knowledge of the pregnant women on malaria in pregnancy and IPTp was average and is likely to have an impact on the low IPTp coverage. Campaigns that provide educational massages on the risk of malaria during pregnancy and the usefulness of IPTp need to be emphasised.


Mitosis-specific monoclonal antibodies block cleavage in amphibian embryos.
By microinjecting monoclonal antibodies that bind specifically to mitotic and meiotic cells of a variety of species, we studied the biological activity of antigens recognized by these antibodies. The antibodies recognize a family of phosphoprotein antigens that are found throughout the cytoplasm of mitotic cells and particularly at microtubule organizing centers, including centrosomes and kinetochores. Their binding is dependent on phosphorylation of the polypeptides. Immunoglobulins were introduced into Xenopus laevis and Rana pipiens oocytes or cleaving embryos using glass micropipettes. The ability of the antibody-injected oocytes to undergo mitosis or meiosis was compared with those injected with control mouse immunoglobulins. The antibodies failed to block chromosome condensation and germinal vesicle breakdown in progesterone-treated oocytes. However, functional mitotic spindles were not assembled in cleavage stage frog embryos injected with antibodies. In vitro, the binding of the antibodies to the antigens inhibited the dephosphorylation of the antigens by alkaline phosphatase. The antibody binding to the activated microtubule organizing centers (MTOC) seems to block not only the nucleation of microtubules and the organization of the mitotic spindle, but also the dephosphorylation of proteins associated with the MTOC that normally occurs at the mitosis-G1 transition.


Outcomes of medialization laryngoplasty with and without arytenoid adduction.
To evaluate the effect of medialization laryngoplasty (ML) performed alone compared to ML with arytenoid adduction (AA) on glottic gap and voice quality in unilateral vocal fold paralysis (UVFP) patients. Retrospective case series. UVFP patients treated with ML alone and ML with AA at the University of California San Francisco Voice and Swallowing Center were identified. Demographic information and history of laryngeal procedures were collected. Preoperative and postoperative examinations were digitally analyzed using ImageJ for normalized anterior and posterior glottic gap and voice samples graded with CAPE-V scores. Forty-seven patients underwent ML and 27 patients underwent ML with AA. Normalized anterior gap (AG) improved in both ML (preop: 4.4 pixel units (u), postop: 0.8 u; P < 0.001) and ML with AA groups (preop: 3.3 u, postop 0.6 u; P < 0.001). There was no statistically significant difference in normalized AG values between treatment groups. Postoperative normalized posterior gap (PG) improved in the ML with AA group only (preop: 1.8 u, postop: 0.5 u; P = 0.01). Overall severity, roughness, and strain voice parameters had acceptable reliability for analysis. Overall severity improved in ML (preop: 54, postop: 27; P < 0.001) and ML with AA (preop: 44, postop: 24; P = 0.005). There was no statistically significant difference in any voice parameter between treatment groups. UVFP patients undergoing ML may benefit from addition of AA when a large posterior glottic gap is present. In this study, ML with AA but not ML alone resulted in statistically significant improvement in PG. 4. Laryngoscope, 127:2591-2595, 2017.


Ultrastructural localization of angiotensin-converting enzyme in ejaculated human spermatozoa.
Angiotensin-converting enzyme (ACE) is known to be released from human spermatozoa during capacitation. However, it has not yet been localized ultrastructurally in ejaculated sperm cells. Therefore, the purpose of the present study was to demonstrate the location of ACE by means of immunoelectron microscopy and direct immunofluorescence. In addition, ACE activity of spermatozoa was correlated with standard semen parameters. The activity of angiotensin-converting enzyme was measured in spermatozoa from 115 donors and patients attending the andrological outpatient department. Progressive motility was negatively correlated with sperm ACE activity (Spearman rank correlation r=-0.364, P < 0.0001), whereas no statistically significant correlations with sperm concentration, total motility and morphology were observed. Immunoelectron microscopy demonstrated that ACE is mainly located at the plasma membrane of the acrosomal region, equatorial segment, postacrosomal region and midpiece. In contrast, only weak ACE-like immunoreactivity was found at the flagellum. In cases of cells with missing plasma membranes ACE seems also to be located at the surface of the outer acrosomal membrane. By means of immunohistochemical methods, different patterns of ACE-like immunofluorescence were observed: (i) fluorescence of the acrosome or the entire sperm head, midpiece and flagellum; (ii) fluorescence of the postacrosomal region, midpiece and flagellum; (iii) bright fluorescence of the equatorial segment with less intensive labelling of the postacrosomal region and flagellum. Induction of the acrosome reaction by calcium ionophore A23187 resulted in an increase of spermatozoa with weak acrosomal fluorescence, indicating loss of the plasma membrane.


[OREM's self-care deficit theory applied to hypertensive patients].
A study carried out with the objective of evaluating Orem's nursing self-care theory (TDAC) in women with hypertension. Four hypertensive women in an outpatient clinic were interviewed using a form with open and multiple-choice questions on conditioning factors and self-care requirements. The data were analyzed according to the TDAC theoretical framework. Based on the self-care requirements for hypertensive people, the existence or non-existence of adjustment between self-care capacity and self-care need as well as the inhibitors and enhancers of such adjustment were identified. It was concluded that TDAC allowed to identify important aspects related to hypertensive people which must be dealt with by nurses.


Assessing variability of the 24-hour pad weight test in men with post-prostatectomy incontinence.
Decision-making regarding surgery for post-prostatectomy incontinence (PPI) is challenging. The 24-hour pad weight test is commonly used to objectively quantify PPI. However, pad weight may vary based upon activity level. We aimed to quantify variability in pad weights based upon patient-reported activity. 25 patients who underwent radical prostatectomy were prospectively enrolled. All patients demonstrated clinical stress urinary incontinence without clinical urgency urinary incontinence. On three consecutive alternating days, patients submitted 24-hour pad weights along with a short survey documenting activity level and number of pads used. Pad weights collected across the three days were well correlated to the individual (ICC 0.85 (95% CI 0.74-0.93), p<0.001). The mean difference between the minimum pad weight leakage and maximum leakage per patient was 133.4g (95% CI 80.4-186.5). The mean increase in 24-hour leakage for a one-point increase in self-reported activity level was 118.0g (95% CI 74.3-161.7, p<0.001). Pad weights also varied significantly when self-reported activity levels did not differ (mean difference 51.2g (95% CI 30.3-72.1), p<0.001). 24-hour pad weight leakage may vary significantly on different days of collection. This variation is more pronounced with changes in activity level. Taking into account patient activity level may enhance the predictive value of pad weight testing.


OptiDock: virtual HTS of combinatorial libraries by efficient sampling of binding modes in product space.
Products from combinatorial libraries generally share a common core structure that can be exploited to improve the efficiency of virtual high-throughput screening (vHTS). In general, it is more efficient to find a method that scales with the total number of reagents (Sigma growth) rather with the number of products (Pi growth). The OptiDock methodology described herein entails selecting a diverse but representative subset of compounds that span the structural space encompassed by the full library. These compounds are docked individually using the FlexX program (Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. J. Mol. Biol. 1995, 251, 470-489) to define distinct docking modes in terms of reference placements for combinatorial core atoms. Thereafter, substituents in R-cores (consisting of the core structure substituted at a single variation site) are docked, keeping the core atoms fixed at the coordinates dictated by each reference placement. Interaction energies are calculated for each docked R-core with respect to the target protein, and energies for whole compounds are calculated by finding the reference core placement for which the sum of corresponding R-core energies is most negative. The use of diverse whole compounds to define binding modes is a key advantage of the protocol over other combinatorial docking programs. As a result, OptiDock returns better-scoring conformers than does serially applied FlexX. OptiDock is also better able to find a viable docked pose for each library member than are other combinatorial approaches.


Amino-terminal amino acid sequence of human leukocyte interferon.
We report the amino-terminal sequence of the first 22 amino acids of human leukocyte interferon. These and other results indicate that human leukocyte interferon consists of many individual species. We, therefore, postulate that diversity in this protein is routinely present and that the human leukocyte interferons represent a multigene family.


Expression of genes encoding antimicrobial and bradykinin-related peptides in skin of the stream brown frog Rana sakuraii.
Peptidomic analysis of an extract of the skin of the stream brown frog Rana sakuraii Matsui and Matsui, 1990 led to the isolation of a C-terminally alpha-amidated peptide (VR-23; VIGSILGALASGLPTLISWIKNR x NH2) with broad-spectrum antimicrobial activity that shows structural similarity to the bee venom peptide, melittin together with two peptides belonging to the temporin family (temporin-1SKa; FLPVILPVIGKLLNGIL x NH2 and temporin-1SKb; FLPVILPVIGKLLSGIL x NH2), and peptides whose primary structures identified them as belonging to the brevinin-2 (2 peptides) and ranatuerin-2 (1 peptide) families. Using a forward primer that was designed from a conserved region of the 5'-untranslated regions of Rana temporaria preprotemporins in a 3'-RACE procedure, a cDNA clone encoding preprotemporin-1SKa was prepared from R. sakuraii skin total RNA. Further preprotemporin cDNAs encoding temporin-1SKc (AVDLAKIANIAN KVLSSL F x NH2) and temporin-1SKd (FLPMLAKLLSGFL x NH2) were obtained by RT-PCR. Unexpectedly, the 3'-RACE procedure using the same primer led to amplification of a cDNA encoding a preprobradykinin whose signal peptide region was identical to that of preprotemporin-1SKa except for the substitution Ser18-->Asn. R. sakuraii bradykinin ([Arg0,Leu1,Thr6,Trp8] BK) was 28-fold less potent than mammalian BK in effecting B2 receptor-mediated relaxation of mouse trachea and the des[Arg0] derivative was only a weak partial agonist. The evolutionary history of the Japanese brown frogs is incompletely understood but a comparison of the primary structures of the R. sakuraii dermal peptides with those of Tago's brown frog Rana tagoi provides evidence for a close phylogenetic relationship between these species.


Synthesis of 'cineole cassette' monoterpenes in Nicotiana section Alatae: gene isolation, expression, functional characterization and phylogenetic analysis.
The scent bouquets of flowers of Nicotiana species, particularly those of section Alatae, are rich in monoterpenes, including 1,8-cineole, limonene, β-myrcene, α- and β-pinene, sabinene, and α-terpineol. New terpene synthase genes were isolated from flowers of Nicotiana bonariensis, N. forgetiana, N. longiflora, and N. mutabilis. The recombinant enzymes synthesize simultaneously the characteristic 'cineole cassette' monoterpenes with 1,8-cineole as the dominant volatile product. Interestingly, amino acid sequence comparison and phylogenetic tree construction clustered the newly isolated cineole synthases (CIN) of section Alatae together with the catalytically similar CIN of N. suaveolens of section Suaveolentes, thus suggesting a common ancestor. These CIN genes of N. bonariensis, N. forgetiana, N. longiflora, and N. mutabilis are distinct from the terpineol synthases (TERs) of the taxonomically related N. alata and N. langsdorfii (both Alatae), thus indicating gene diversification of monoterpene synthases in section Alatae. Furthermore, the presence of CINs in species of the American section Alatae supports the hypothesis that one parent of the Australian section Suaveolentes was a member of the present section Alatae. Amino acid sequences of the Nicotiana CINs and TERs were compared to identify relevant amino acids of the cyclization reaction from α-terpineol to 1,8-cineole.


Large visuospatial sex difference in line judgment: possible role of attentional factors.
This article describes a large sex difference on a new, group-administered visuospatial task, the Judgment of Line Angle and Position (JLAP) test, and investigates the role of attentional factors in the difference. On the JLAP, adapted from a neuropsychological task (Benton et al., 1983), participants evaluate spatial attributes of lines. Study 1: College males (N = 48) outperformed females (N = 80), resulting in a large effect for sex (d = 0.85). Errors were more common on oblique (vs horizontal or vertical) lines, especially for females. Study 2: Task attributes were manipulated (N = 33 males and 36 females) to study the role of attentional factors. Findings suggest that males are more likely than females to normally attend to and be aided by geometrical reference cues.


The ubiquity of big brother.
Teachers from grades K through 6 nominated the most physically active and most physically passive students from each sex. Half the schools were attended mainly by low-SES Mexican-American students and half upper-middle-SES Caucasian students. The main finding was that physically active students were more likely to have an older brother than were physically passive students. This effect was independent of sex, grade level, race, SES, and other-sibling combinations. A second study confirmed this relationship when college students rated themselves on the same active-passive dimension.


Insulin-like growth factor-I gene polymorphism in acne vulgaris.
Acne vulgaris is a multifactorial disease of the skin. Several studies have shown that elevated levels of serum insulin-like growth factor-I (IGF-I) correlate with overproduction of sebum and acne. Recently functional relationship between IGF-I (CA) polymorphism and circulating IGF-I levels in adults has been reported. The aim of our study was to investigate for the first time whether IGF-I (CA) polymorphism might be involved in the pathogenesis of acne or not. We included 115 acne patients and 117 healthy subjects to the study. The clinical grade of acne was assessed based on the Global Acne Grading System. Participants were questioned about diabetes mellitus, PCOS and other systemic disease. We searched for the IGF-I (CA) 19 polymorphism in this study. The IGF-I (CA) 19 polymorphism was performed by polymerase chain reaction. We categorized the IGF-I (CA) 19 polymorphism area into three groups as lower than 192 bp, 192–194 bp and higher than 194 bp. We found that the frequency of genotype IGF-1 (CA) 19 gene was significantly different between control and acne patients (P = 0.0002). A significant association between IGF-I (CA) genotypes and severity of acne was found (P = 0.015). No significant difference was found between male and female patients (P > 0.05). Our results suggest that IGF-I (CA) 19 polymorphism may contribute to a predisposition to acne in Turkish patients.


B virus-specific pathogen-free (SPF) breeding colonies of macaques: issues, surveillance, and results in 1992.
The NIH's National Center for Research Resources, Comparative Medicine Program has sponsored a multi-institutional program for the establishment of specific pathogen-free (SPF) macaque colonies. Herpes B virus (Cercopithecine herpesvirus I) has been targeted as part of this surveillance. Participating institutions have established individual timetables for frequency of testing, types of monitoring, and husbandry techniques, all with the common goal of producing pathogen-free monkeys for research. From January 1990 through December 1992, we screened animals for evidence of B virus infection, using ELISA and immunoblot to detect humoral antibodies. A total of 984 animals were tested during the first year of the program. At the start of the third year, 631 animals remained in our testing program. Of the 36.9% eliminated for all causes over a 3-year period, B virus screening accounted for 12.1, 1.2, and 0.5% during years 1, 2, and 3, respectively. The greatest threat to the success of the program comes from failure to detect seronegative animals with latent infections, if they do indeed exist, either in first-year animals or animals introduced in subsequent years. The best assurance that a colony is SPF comes from negative results of repeated testing. Introducing new animals into an established SPF colony should be done only after careful screening. Simulations using mathematical models suggest that the best way to detect seronegative animals with latent infections is monthly or bimonthly testing separated by a waiting period. Duration of the waiting period cannot be defined precisely until more is known about the reactivation potential of putative seronegative animals with latent infections.


Ecto- and endo-parasitic monogeneans (Platyhelminthes) on cultured freshwater exotic fish species in the state of Morelos, South-Central Mexico.
An extensive parasitological study of 365 freshwater exotic fish specimens belonging to 13 species of seven families (Cichlidae, Cyprinidae, Osphronemidae, Pangasidae, Poeciliidae, Characidae, and Loricariidae) collected from 31 Aquaculture Production Units (APU) from Central Mexico revealed the occurrence of 29 ecto- and endo-parasitic monogeneans found on gills and stomachs: Cichlidogyrussclerosus, C.thurstonae, C.tilapiae, Cichlidogyrus sp. 1, Cichlidogyrus sp. 2, Enterogyruscoronatus, E.malmbergi, Gusseviaspiralocirra, Sciadicleithrumiphthimum, Sciadicleithrum sp., Scutogyruslongicornis (all Dactylogyridae), Gyrodactyluscichlidarum, and G.yacatli (Gyrodactylidae) on Oreochromisniloticus, Pterophyllumscalare and Hemichromis sp. (Cichlidae); Dactylogyrusbaueri, D.formosus, D.intermedius, D.vastator, D.extensus, Dactylogyrus sp. (all Dactylogyridae), and G.kobayashii on Carassiusauratus, Cyprinuscarpio and Ctenopharyngodonidella (Cyprinidae); Trianchoratusacleithrium and T.trichogasterium (Dactylogyridae) on Trichogastertrichopterus (Osphronemidae); Thaparocleiduscaecus, T.siamensis (Dactylogyridae), and Dactylogyridae sp. on Pangasianodonhypophthalmus (Pangasidae); G.poeciliae on Poeciliareticulata (Poeciliidae); Diaphorocleidusarmillatus (Dactylogyridae) on Gymnocorymbusternetzy (Characidae); Unilatusunilatus (Dactylogyridae) and Gyrodactylidae sp. on Hypostomus sp. (Loricariidae). The paramount importance of the establishment of these monogeneans due to the importation/exportation of non-native ornamental and other exotic host fish species cultured for food in Mexico is briefly discussed. Quarantine is recommended for all transferred host species.


Risk factors for hospital-acquired infections in teaching hospitals of Amhara regional state, Ethiopia: A matched-case control study.
Hospital-acquired infection affects hundreds of millions of people worldwide. It is a major global issue for patient safety. Understanding the potential risk factors is important to appreciate the local context. A matched case control study design, which is the first of its kind in the study region, was undertaken to identify risk factors in teaching hospitals of Amhara regional state, Ethiopia. A matched case control study design matched with age and hospital type was used. The study was conducted in University of Gondar and Felege-Hiwot medical teaching hospital. Cases were patients who fulfilled the criteria based on CDC definition of hospital-acquired infection and controls were patients admitted to the hospital that stayed for more than 48 hours in the ward in the study period, but who did not develop infection. For one case, four controls were selected. Of 545 patients, 109 were cases and 436 were controls. Conditional logistic regression using STATA 13 was used for data analysis. The median length of stay for cases and controls was 7 and 8 days, respectively. Patients admitted in wards with the presence of medical waste container in the room had 82% less chance of developing hospital-acquired infection (AOR 0.18; 95% CI, 0.03-0.98). The odds of developing hospital-acquired infection among immune deficient patients were 2.34 times higher than their counterparts (95% CI; 1.17-4.69). Patients received antimicrobials, central vascular catheter and surgery since admission had 8.63, 6.91 and 2.35 higher odds of developing hospital-acquired infection, respectively. Health providers and mangers should consider the provision and availability of healthcare materials and facilities in all of the ward rooms, follow appropriate safe medical procedures for use of external devices on patients, and give attention to the immunocompromised patients for the prevention and control of hospital-acquired infections.


Implementation and preliminary testing of a theory-guided nursing discharge teaching intervention for adult inpatients aged 50 and over with multimorbidity: a pragmatic feasibility study protocol.
Discharge teaching by nurses during hospitalization is essential to provide multimorbid inpatients with the knowledge and skills to self-manage their health conditions. However, available disease-specific teaching guidelines do not address the cumulative complexity of multiple chronic diseases that occur with greater frequency in older adults. Therefore, there is a need for a discharge teaching intervention which uses concepts that specifically address the needs of these patients, such as considering their level of activation (i.e. knowledge, skills and confidence to self-manage their health) and the burden of multimorbid disease. The objectives of this pragmatic study will be to (1) test the feasibility of implementing a nursing discharge teaching intervention and (2) conduct a preliminary test of this novel discharge teaching intervention with adult inpatients age 50 or greater who have multiple comorbid conditions. This study uses a two-group pre-posttest design. Participants are drawn from medical units in three hospitals in the French-speaking part of Switzerland. The implementation of the intervention will be facilitated by implementation strategies from the Theoretical Domains Framework and the Behavior Change Wheel and will target change in nurses' teaching behaviours. Implementation outcomes will include measures of feasibility of the implementation strategies and the intervention process. Participants in the intervention group will receive tailored discharge teaching by trained teaching nurses. Patient outcomes will inform the preliminary testing of the intervention and will be measured with validated questionnaires assessing patients' activation level, health confidence, perceived readiness for discharge, experience with the discharge process and rate of and time to readmission. The study takes a pragmatic approach to examining the feasibility of implementing the discharge teaching intervention to contribute to the knowledge development within the context of the real-world practice setting. Results will provide the foundation for clinical trials to build evidence for widespread adoption of this intervention. The trial is registered at ClinicalTrials.gov (ID: NCT04253665 ) on the 30 of January 2020 and has been approved by the Cantonal Ethics Committee Vaud in Switzerland (2020-00141).


Critical particle size where the Stokes-Einstein relation breaks down.
The validity of the Stokes-Einstein (SE) relation for particle diffusion in the nano- and molecular scales has attracted much interest, but the results in the literature are controversial. In this work, it is shown that there exists a critical particle size where the SE relation breaks down by comparing particle transport in the macro- and molecular scales. Using molecular-dynamics simulations, we study the critical size and find that the van der Waals force plays an important role in particle diffusion as the particle size approaches molecular scale. Due to the limitations of computing facilities, we could not find exactly where the critical particle size is, but the simulation results qualitatively predict that this critical size is of a few nanometers.


Ablation of the microRNA-17-92 cluster in neural stem cells diminishes adult hippocampal neurogenesis and cognitive function.
Impairment of adult neurogenesis in the hippocampus causes cognitive deficits; however, the underlying molecular mechanisms have not been fully elucidated. microRNAs (miRNAs) regulate neural stem cell (NSC) function. With the use of a transgenic mouse line with conditional ablation of the miR-17-92 cluster in nestin lineage NSCs, we tested the hypothesis that the miR-17-92 cluster regulates adult neurogenesis and cognitive function in vivo. Compared with wild-type mice, ablation of the miR-17-92 cluster significantly reduced the number of proliferating NSCs and neuroblasts and neuronal differentiation in the dentate gyrus (DG) of the hippocampus and significantly impaired hippocampal-dependent learning and memory, as assayed by social recognition memory, novel object recognition, and Morris water-maze tests. Statistical analysis showed a highly significant correlation between newly generated neuroblasts in the DG and cognition deficits in miR-17-92 knockout (KO) mice. Western blot analysis showed that conditional KO of the miR-17-92 cluster significantly increased and reduced a cytoskeleton-associated protein, Enigma homolog 1 (ENH1), and its downstream transcription factor, inhibitor of differentiation 1 (ID1), respectively, as well as increased phosphatase and tensin homolog gene. These proteins are related to neuronal differentiation. Our study demonstrates that the miR-17-92 cluster in NSCs is critical for cognitive and behavioral function and regulates neurogenesis and that the miR-17-92 cluster may target ENH1/ID1 signaling.-Pan, W. L., Chopp, M., Fan, B., Zhang, R., Wang, X., Hu, J., Zhang, X. M., Zhang, Z. G., Liu, X. S. Ablation of the microRNA-17-92 cluster in neural stem cells diminishes adult hippocampal neurogenesis and cognitive function.


The age-related performance decline in marathon cross-country skiing - the Engadin Ski Marathon.
Demographic and performance data from 197,825 athletes competing in "Engadin Ski Marathon" between 1998 and 2016 were analysed. When all finishers per age group were considered, there was no gender difference in time (2:59:00 in women versus 2:59:09 h:min:s in men; P = 0.914, η2 < 0.001) and the main effect of age group on time was trivial (P < 0.001, η2 = 0.007). When the top 10 finishers per age group were considered, men were faster than women (1:27:32 versus 1:34:19 h:min:s, respectively; P < 0.001, η2 = 0.373), there was a large effect of age group on time (P < 0.001, η2 = 0.590) and the gender difference was larger in the older than in the younger age groups (P < 0.001, η2 = 0.534). The age of peak performance for all finishers by 1-year interval age group was 40.3 and 39.6 years in all women and men, respectively. The top 10 finishers by 1-year interval age group achieved their peak performance in the age of 38.4 and 42.2 years in women and men, respectively. The age of peak performance was older and the age-related performance decline occurred earlier in marathon cross-country skiing, compared to road-based marathon running.


A modern plan for treating hypertension.
Essential hypertension is a heterogeneous spectrum of pathophysiologic disturbances, not a single entity. Identification and characterization of two different vasoconstrictor mechanisms--one renin-mediated, the other sodium-volume mediated--has made it possible not only to apply antihypertensive drug therapy on a more rational basis but to screen out a significant number of cases of curable (high-renin) renovascular disease as well as many cases of curable (low-renin) primary aldosteronism. An array of five major drug types makes long-term monotherapy for essential hypertension an achievable goal. Converting enzyme inhibitors and beta-blockers counteract the renin-mediated vasoconstriction; diuretics, calcium-channel antagonists, and alpha-blockers oppose the low-renin sodium-volume-mediated form of vasoconstriction. This information brings us closer to the primary goal of modern therapy: to give each patient the fewest drugs in the smallest amounts and with the least frequency possible for the often lifetime commitment that antihypertensive therapy involves.


Role of donor MHC class III genes in the destruction of transplanted islets in NOD mice.
MHC class III genes are important in immune regulation and inflammation, and the gene products of this region are well conserved between species. Their role in diabetes is, however, unknown. We used islets from NOD mice that lacked expression of both MHC class I and class II molecules to test the effect of class III differences on the injury of transplanted NOD islets. Loss of islet MHC class I was highly protective, while deletion of MHC class II had no benefit on islet survival. However the combined absence of both MHC class I and class II expression by NOD islets resulted in a delayed form of injury, when islets were transplanted to NOD mice. As neither MHC class I or II molecules were expressed by donor islet tissue, these results suggest a previously unrecognized and important contribution of MHC class III differences on islet injury following transplantation.


In vitro antimicrobial effects of Hypoxis hemerocallidea against six pathogens with dermatological relevance and its phytochemical characterization and cytotoxicity evaluation.
Hypoxis hemerocallidea (commonly known as African Potato) is popular in African traditional medicine. It is used in the management of diverse ailments including burns, wounds and skin-related diseases. The current study investigated the antimicrobial effects of Hypoxis hemerocallidea against six microorganisms associated with skin diseases. In addition, the antioxidant activity, phytochemical profiles and cytotoxicity of the bulb extracts were evaluated. The antimicrobial activity of 50% methanol (MeOH) and petroleum ether (PE) extracts of Hypoxis hemerocallidea bulbs was tested against two bacterial and four fungal strains implicated in causing opportunistic skin-related diseases. Antioxidant potential of the extract was investigated via the 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging assay and β-carotene linoleic acid model. Phytochemical profiling of the 50% MeOH extract of Hypoxis hemerocallidea was done using spectrophotometric assay and Gas Chromatography-Mass Spectrometry (GC-MS). The extracts were also evaluated for cytotoxicity against African green monkey Vero kidney cell lines based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Both 50% MeOH and PE extracts showed considerable inhibitory effects against all six microorganisms. The extracts were potent against Shigella flexneri and Trichophyton tonsurans with minimum inhibitory concentration (MIC) values less than 1 mg/ml. However, there was relatively poor antifungal activity against the other fungal strains. In the DPPH assay, the MeOH extract of the bulb had an EC50 of 29.8 μg/ml while 76.91% antioxidant activity was observed in the β-carotene-linoleic acid model. The extract contained total phenolics (41 mg GAE/g) and flavonoids (10 mg CE/g). The GC-MS analysis of Hypoxis hemerocallidea bulb revealed 29 and 160 bioactive compounds for 50% MeOH and PE extracts, respectively. Based on the cytotoxicity, Hypoxis hemerocallidea had LC50 value of 210.9 ± 18.4 and 95.5 ± 13.3 μg/ml for PE and MeOH extracts, respectively. The bulb extracts of Hypoxis hemerocallidea exhibited good antimicrobial and antioxidant activities, which could be attributed to the presence of phenolics, flavonoids and the other bioactive compounds identified through GC-MS, making it a potentially effective cosmetic plant. These findings also account for the multi-pharmacological use of Hypoxis hemerocallidea in traditional medicine, especially related to skin diseases. The plant extracts can be considered as safe based on their LC50 values (< 20 μg/ml). However, other form of cytotoxicity studies need to be carried out on Hypoxis hemerocallidea, as well as in vivo tests, to confirm its safety and efficacy as a treatment for skin-related diseases.


Band gap change and interfacial reaction in Hf-silicate film grown on Ge(001).
The interfacial reaction of hafnium-silicate [(HfO(2))(x)(SiO(2))(1-x), x=0.5,0.7] thin films grown on Ge(001) by atomic layer deposition was investigated using x-ray photoelectron spectroscopy and medium energy ion scattering spectroscopy. According to the peak changes in Hf 4f and Ge 3d, the Hf-silicate film reacted with the oxidized Ge surface forming Hf-germanate at the interface. The formation of Hf-germanate induced band bending of the Ge substrate at the interface and decreased band gap to 5.1 eV, which was lower than that of GeO(2) (5.6 eV). In particular, the interfacial reaction was dependent on the amount of SiO(2) in the Hf-silicate film, which resulted in more decrement in the band gap in the film with a high SiO(2) fraction.


Strategies to increase the efficacy of using gut microbiota for the modulation of obesity.
Obesity is one of the most serious global public health challenges of the 21st century. The adjustment of gut microbiota is often recommended as an efficient strategy to treat obesity. This modulation of gut microbiota can be performed by many methods, including dietary intervention, antibiotic application, the use of prebiotics and probiotics, bariatric surgery and faecal microbiota transplantation. In most cases, positive effects have been observed in response to treatment, but invalid and even contrary effects have also been observed in some cases due to factors that are unrelated to intervention methods, such as genetic factors, patient age or gender, environmental microbiota, climate, geography and lifestyle. These factors can cause variation of gut microbial populations and thus should also be taken into consideration when selecting modulation strategies.


Changes in susceptibility to conventional insecticides of a Cry1Ac-selected population of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae).
The changes in the susceptibility of the cotton bollworm, Helicoverpa armigera (Hübner) to three insecticides (lambda-cyhalothrin, phoxim and endosulfan) commonly used for control of this pest in China were monitored by bioassays at various generations. The insects were originally collected from Bt cotton fields and selected with Cry1Ac over 44 generations. In comparison with a susceptible strain, the larval resistance of the Bt-selected populations to Cry1Ac toxin increased 106-fold. Simultaneously, the resistance levels to lambda-cyhalothrin, phoxim and endosulfan declined dramatically. The results indicated no positive cross-resistance between Cry1Ac toxin and the insecticides. Evidence of the lack of cross-resistance to three commonly used synthetic insecticides in our laboratory-derived Cry1Ac-resistant population may suggest that growers can confidently use these insecticides if and when resistance to Cry1Ac cotton does occur.


Soluble Two-Dimensional Covalent Organometallic Polymers by (Arene)Ruthenium-Sulfur Chemistry.
A class of two-dimensional (2D) covalent organometallic polymers, with nanometer-scale crosslinking, was obtained by arene(ruthenium) sulfur chemistry. Their ambivalent nature, with positively charged crosslinks and lypophylic branches is the key to the often sought-for and usually hard-to-achieve solubility of 2D polymers in various kinds of solvents. Solubility is here controlled by the planarity of the polymer, which in turn controls Coulomb interactions between the polymer layers. High planarity is achieved for high symmetry crosslinks and short, rigid branches. Owing to their solubility, the polymers are easily processable, and can be handled as powder, deposited on surfaces by mere spin-coating, or suspended across membranes by drop-casting. The novel 2D materials are potential candidates as flexible membranes for catalysis, cancer therapy, and electronics.


Hide and seek: does the toe-brachial index allow for earlier recognition of peripheral arterial disease in diabetic patients?
Arterial calcification may render the ankle-brachial index (ABI) unreliable in diabetic patients. Although guidelines recommend the toe-brachial index (TBI) for patients with falsely elevated ABI arbitrarily defined as an ABI > 1.4, arterial calcification is also common among diabetic patients with an ABI ≤ 1.4. This could result in a "falsely normalized" ABI and under-diagnosis of peripheral arterial disease (PAD). We investigated whether diabetes invalidates the ABI as opposed to the TBI, and if the TBI may therefore be more suitable for detecting PAD in diabetic patients. The difference between ABI and TBI was compared between diabetic and non-diabetic patients with an ABI ≤ 1.4 referred to the vascular laboratory. A Bland-Altman plot was constructed to assess whether ABI-TBI differences were dependent on the magnitude of the measurements. Subgroup analyses were performed for patients with a normal ABI, and for patients with critical ischemia. The population comprised 161 diabetic (252 limbs) and 160 non-diabetic (253 limbs) patients (mean age 67). Median ABIs (0.79 vs. 0.80) were similar, while median TBI was 0.07 higher in diabetics (p = 0.024). The ABI-TBI difference in diabetics and non-diabetics was similar (0.32 vs. 0.35; p = .084), and was also similar for patients with a normal ABI. Moreover, ABI-TBI differences in diabetic- and non-diabetic patients overlapped, irrespective of the magnitude of the measurements. Diabetes was not associated with larger differences between ankle and toe pressures (mean difference -0.9 mmHg, 95% confidence interval -15 to 13 mmHg) among patients with critical ischemia. No evidence was found that the TBI may overcome the potentially invalidated ABI in diabetic patients with an ABI ≤ 1.4. ABI and TBI are strongly associated, and this relationship is not influenced by diabetes. Therefore, the TBI does not allow for earlier detection of ischemia in diabetes.


Reviewing the technical designs for experiments with ultraviolet-B radiation and impact on photosynthesis, DNA and secondary metabolism.
The ultraviolet-B (UV-B) portion of sunlight has received much attention in the last three decades, because radiation from this spectral region increases due to the stratospheric ozone depletion, which results from increases of chlorofluorocarbons in the atmosphere. Plant responses to UV-B exposure vary greatly and the interpretation of and comparison between studies is hindered, mainly by the contrasting experimental conditions used and interactive factors such as low light levels and possible artifacts due to the artificial experimental conditions. It seems likely that increases in solar UV-B radiation of the magnitude anticipated under current stratospheric ozone projections will not significantly inhibit photosynthesis and cause DNA damage in plants. This is in part due to the well-evolved protection mechanisms present in most plant species. One of the significant plant responses to UV-B is changes in foliar secondary chemistry, which could be translated into significant effects at higher trophic levels through plant-herbivore interactions and decomposition. Enhanced UV-B radiation due to stratospheric ozone depletion could also cause morphological changes that would affect competitive interactions, especially if contrasting UV-B sensitivity exists among the competitors.


Using a handheld stereo depth camera to overcome limited field-of-view in simulation imaging for radiation therapy treatment planning.
A correct body contour is essential for reliable treatment planning in radiation therapy. While modern medical imaging technologies provide highly accurate patient modeling, there are times when a patient's anatomy cannot be fully captured or there is a lack of easy access to computed tomography (CT) simulation. Here, we provide a practical solution to the surface contour truncation problem by using a handheld stereo depth camera (HSDC) to obtain the missing surface anatomy and a surface-surface image registration to stich the surface data into the CT dataset for treatment planning. For a subject with truncated simulation CT images, a HSDC is used to capture the surface information of the truncated anatomy. A mesh surface model is created using a software tool provided by the camera manufacturer. A surface-to-surface registration technique is used to merge the mesh model with the CT and fill in the missing surface information thereby obtaining a complete surface model of the subject. To evaluate the accuracy of the proposed approach, experiments were performed with the following steps. First, we selected three previously treated patients and fabricated a phantom mimicking each patient using the corresponding CT images and a 3D printer. Second, we removed part of the CT images of each patient to create hypothetical cases with image truncations. Next, a HSDC was used to image the 3D-printed phantoms and the HSDC-derived surface models were registered with the hypothetically truncated CT images. The contours obtained using the approach were then compared with the ground truth contours derived from the original simulation CT without image truncation. The distance between the two contours was calculated in order to evaluate the accuracy of the method. Finally, the dosimetric impact of the approach is assessed by comparing the volume within the 95% isodose line and global maximum dose (Dmax ) computed based on the two surface contours for the breast case that exhibited the largest contour variation in the treated breast. A systematic strategy of using a 3D HSDC to compensate for missing surface information caused by the truncation of CT images was established. Our study showed that the proposed technique was able to reliably provide the full contours for treatment planning in the case of severe CT image truncation(s). The root-mean-square error for the registration between the aligned HDSC surface model and the ground truth data was found to be 2.1 mm. The average distance between the two models was 0.4 ± 1.7 mm (mean ± SD). Maximum deviations occurred in areas of high concavity or when the skin was close to the couch. The breast tissue covered by 95% isodose line decreased by 3% and Dmax increased by 0.2% with the use of the HSDC model. The use of HSDC for obtaining missing surface data during simulation has a number of advantages, such as, ease of use, low cost, and no additional ionizing radiation. It may provide a clinically practical solution to deal with the longstanding problem of CT image truncations in radiation therapy treatment planning.


The Effectiveness of Cognitive Behavioral Therapy versus Psychoeducation in the Management of Depression among Patients Undergoing Haemodialysis.
The aim of this randomized controlled trial was to compare the effectiveness of psychoeducation versus cognitive behavioral therapy (CBT) in the management of depression among renal dialysis patients. A sample of 130 dialysis patients participated in the study and they were assigned at random to one of two therapies: psychoeducation (N = 65) or CBT (N = 65). Hamilton depression rating scale was completed by the participants in both groups prior to the therapies and after completion. Both therapies were effective in the management of depression, although psychoeducation was superior. Psychoeducation is recommended over CBT in the management of depression among renal dialysis patients.


The role of the district medical officer after the pandemic - a qualitative study.
While district medical officers' role was described as unclear and lacking visibility before the COVID-19 pandemic, their community medicine expertise became highly significant in the management of the pandemic. We wished to investigate district medical officers' perceptions of their role after the pandemic was over. The study was designed as a theory-driven qualitative interview study. Twelve district medical officers in the Norwegian county of Innlandet were interviewed in the autumn of 2022. The data were subjected to thematic analysis. The study identified a number of factors associated with the capabilities, motivation, and structural and organisational framework of district medical officers that were assumed to impact on the execution of their role and participation in decision-making processes in the local authorities. The district medical officers found that their role had become clearer and more visible during the pandemic, but they had low expectations of being more involved and having a stronger voice in the development of future health services in the municipalities. One proposed measure is to devise a guide for the district medical officer function, such that the local authorities are given clear guidelines on the district medical officers' areas of responsibility and the issues in which they should be involved. The district medical officers felt that 'the pandemic effect is over', and that they had to fight their way back into important decision-making arenas. Measures at individual and organisational level can help ensure the optimal use of district medical officers' community medicine expertise in the municipalities.


[Methodological issues of health research].
This work aims at presenting a reflection on the method of research in the health field. Some questions are presented which involve the use of the method of natural sciences and that of social sciences in an attempt at understanding some methodological problems concerning the former and the latter. Problems related to the methodological issues in the elaboration of investigation projects in this field and the need for continuous discussion are pointed out as to: the differentiation of the nature of the object of investigation; the context in which a determined problem is identified; the type of question which is asked when it is problematized; technical procedures, the theory and the interpretative scheme on which it is founded; the dichotomy concerning the subject/object of knowledge; the researcher's neutrality; the concept of casualty.


Shogaols from Zingiber officinale protect IMR32 human neuroblastoma and normal human umbilical vein endothelial cells from beta-amyloid(25-35) insult.
From the rhizome of Zingiber officinale L. (Zingiberaceae), four shogaols that protect IMR32 human neuroblastoma and normal human umbilical vein endothelial cells from beta-amyloid(25 - 35) insult at EC50 = 4.5 - 81 microM were isolated. The efficacy of cell protection from beta-amyloid(25 - 35) insult by these shogaols was shown to improve as the length of the side chain increases.


Construed external image and organizational identification: a test of the moderating influence of need for self-esteem.
According to Social Identity Theory (cf., J. G. March & H. A. Simon, 1958), individuals tend to identify with prestigious or high-status groups. Researchers (J. E. Dutton, J. M. Dukerich, & C. V. Harquail, 1994) have revealed that organizational members also identify with organizations that have attractive public images. To gain a better understanding of the theoretical reasons underlying the relationship between image and identification in organizations, the authors examined this relationship in a healthcare setting. In addition, they investigated need for esteem as a moderator of the relationship between construed external image and organizational identification. Consistent with previous findings, the present results indicated that construed external image is positively related to organizational identification. Perhaps it is more important that the present findings also supported need for esteem as a moderator of the relationship between construed external image and organizational identification.


Full and Short Versions of the Coping Inventory for Stressful Situations and Social Problem-Solving Inventory-Revised: Examining Their Factor Structure in a Dutch Outpatient Sex Offender Sample.
Inadequate problem solving is associated with recidivism in sex offenders. However, the psychometric properties of two of the most widely used coping self-report questionnaires, the Social Problem-Solving Inventory-Revised and Coping Inventory for Stressful Situations, have not been established for outpatient sex offenders. Using structural equation modeling, the present study aims to contribute to an empirically based decision as to which version of the Coping Inventory for Stressful Situations or Social Problem-Solving Inventory-Revised is best suited to use with forensic outpatient sex offenders. The sample consisted of 530 Dutch sex offenders treated in an outpatient forensic facility. Results support the use of the Coping Inventory for Stressful Situations-Short Form 20 for identifying problem-solving deficits among outpatient sex offenders, consequently facilitating the assessment of treatment needs.


Gene expression signatures and molecular markers associated with clinical outcome in locally advanced head and neck carcinoma.
The purpose of this study was to identify molecular markers associated with tumor recurrence and survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). We studied the expression profile of 63 pre-treatment tumor biopsies obtained from locally advanced HNSCCs treated with standard treatments. Cluster analysis identified three tumor subtypes associated with significant differences in local recurrence-free survival (LRFS) (P<0.001), progression free-survival (PFS) (P<0.009) and overall survival (OS) (P<0.004). Tumor subtype 1, associated with short LRFS, PFS and OS, showed features of epithelial-mesenchymal transition and undifferentiation. It also overexpressed genes involved in cell adhesion, NF-κB and integrin signalling. Tumor subtype 3, associated with longer LRFS, PFS and OS, showed a high degree of differentiation and overexpressed genes located in chromosomal regions 19q13 and 1q21. Tumor subtype 2, which had an intermediate clinical outcome between subtype 1 and subtype 3, overexpressed genes involved in branching morphogenesis. Finally, we validated the association between gene cluster classification and patient survival using Gene Set Enrichment Analysis and two HNSCC data sets obtained from two independent patient cohorts. In conclusion, we generated a gene prognostic signature associated with survival in locally advanced patients using the expression profile of the pre-treatment tumor biopsy. Independent prospective studies would be necessary to assess if the proposed survival signature could help to guide clinical management of HNSCC.


Esophageal electric fields are predictive of atrial cardioversion success-a finite element analysis.
Atrial fibrillation (AF) is a debilitating cardiac arrhythmia, one potential treatment of which is external cardioversion. Studies have shown external cardioversion success is affected by electrode placement and that esophageal electric fields (EEFs) during low strength shocks have the potential to be used in determining patient-specific optimal electrode placements during animal experiments. The objective of this study was to determine the relationship between EEFs and atrial defibrillation thresholds (ADFTs) during computer simulations using an anatomically realistic computer model of a human torso. Over 600 electrode placements were simulated during which EEFs were compared to ADFTs. There was no single optimal electrode placement with multiple electrode placements resulting in similarly low ADFTs. There was over 40% difference in the ADFTs between the most and least optimal electrode configurations. There was no correlation between EEFs and ADFTs for all electrode placements, but a strong negative correlation when small shifts from clinically relevant electrode placements were performed. These results suggest a small shifts protocol from clinically relevant electrode placements has the potential to increase the probability of successful cardioversion on the first shock and reduce the cumulative number of shocks and energy to which patients are exposed.


Ventricular fibrillation causes sudden death in Southeast Asian immigrants.
Young, male, Southeast Asian immigrants living in the United States have a high incidence of unexplained, sudden, nocturnal death. We report the cases of three patients, two Laotians and one Filipino, who were resuscitated and subsequently studied extensively. Each patient was having ventricular fibrillation when first examined by paramedics outside the hospital, and episodes of fibrillation recurred in the early hospital course. Clinical evaluation found no significant coronary atherosclerosis or structural cardiac disease. One patient is asymptomatic after 2 years; the second patient died suddenly at 4 months; and the third is asymptomatic but had inducible ventricular tachycardia on electrophysiologic testing 6 months after resuscitation. The mechanism of sudden death in young Southeast Asian men appears to be ventricular fibrillation. The cause of the arrhythmia is unclear, although in our patients the arrhythmia was not an isolated event; underlying predispositions to further cardiac arrest persisted.


Describing the diversity of Ag specific receptors in vertebrates: Contribution of repertoire deep sequencing.
During the last decades, gene and cDNA cloning identified TCR and Ig genes across vertebrates; genome sequencing of TCR and Ig loci in many species revealed the different organizations selected during evolution under the pressure of generating diverse repertoires of Ag receptors. By detecting clonotypes over a wide range of frequency, deep sequencing of Ig and TCR transcripts provides a new way to compare the structure of expressed repertoires in species of various sizes, at different stages of development, with different physiologies, and displaying multiple adaptations to the environment. In this review, we provide a short overview of the technologies currently used to produce global description of immune repertoires, describe how they have already been used in comparative immunology, and we discuss the future potential of such approaches. The development of these methodologies in new species holds promise for new discoveries concerning particular adaptations. As an example, understanding the development of adaptive immunity across metamorphosis in frogs has been made possible by such approaches. Repertoire sequencing is now widely used, not only in basic research but also in the context of immunotherapy and vaccination. Analysis of fish responses to pathogens and vaccines has already benefited from these methods. Finally, we also discuss potential advances based on repertoire sequencing of multigene families of immune sensors and effectors in invertebrates.


Transvaginal Reduction of a Heterotopic Cornual Pregnancy with Conservation of Intrauterine Pregnancy.
Here we report a case of heterotopic cornual pregnancy after in vitro fertilization who was diagnosed at 6 weeks after frozen embryos transfer. The heterotopic pregnancy was successfully terminated by transvaginal ultrasound-guided selective fetal reduction. At 38+1 weeks, she underwent a cesarean section and delivered a healthy 3300 g male infant with Apgar score of 10-10' evaluated at 1 min and 5 min.


[Clinicopathologic and cytogenetic features of 114 Chinese mantle cell lymphoma cases].
To study the clinicopathologic features, immunotype and cytogenetics of Chinese mantle cell lymphoma (MCL). 114 MCL cases were collected from hematopathology lab of department of pathology, Peking University, HSC. Routine HE stain and immune stain were used to investigate the clinicopathologic features and immune type. Breaks of CCND1 and IgH/CCND1 fusion genes were detected by FISH. The ratio of male to female was 3.56:1 (89:25) with the median age of 60 years old (20 - 83 years old). 78 cases (68.42%, 78/114) primarily showed lymph node involvement, including 49 cases (49/78, 62.82%) jugular node involvement; 36 cases (31.58%, 36/114) showed extra-nodal involvement. 23 cases (23/114, 20.18%)showed bone marrow involvement. The expressions of CD3ε, CD20, CD79a, PAX5, CD5, cyclinD1 and Bcl-2 were 0% (0/114), 99.12% (113/114), 96.43% (27/28), 97.56% (40/41), 67.89% (74/109), 100% (114/114) and 94.12% (48/51), respectively. Break of CCND1 gene was found in 20 cases (80%, 20/25), the fusion gene of IgH-CCND1 in 16 cases (80%, 16/20), the break of IgH gene in 9 cases (100%, 9/9)and its fusion gene in 8 cases (88.89%, 8/9). We followed up 75 cases with a period of 2-57 months. The median survival was 40.78 months. The survivals at 1 year, 2 year and 3 year were 84.13% (53/63), 68.09% (32/47) and 37.5% (12/32), respectively. The median survival of group with more than 40% expression of Ki-67 was 36 months, the group with less than 40% expression of Ki67 57 months (P = 0.003). 7 of 13 patients accepted Rituximab plus traditional chemotherapy attained CR, 3 cases PR. 11 of 44 cases accepted traditional chemotherapy attained CR, 9 cases PR (P = 0.052). Most of Chinese MCL occurred in older male, multi-lymphadenopathy and bone marrow involvement were common in MCL as a aggressive tumor. High expression of Ki-67 was an adverse prognostic indicator. Rituximab could improve the survival. Change of CCND1 gene was the most common cytogenetic abnormality.


Determinants of microdamage in elderly human vertebral trabecular bone.
Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54-95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types.


Nocturnal plasma levels of melatonin in quails (Coturnix japonica) injected with l-5-hydroxy-tryptophan.
This study aimed to demonstrate the influence of the systemic administration of l-5-hydroxy-tryptophan (L-HTP) on the plasma levels of melatonin during the dark period in quails. Throughout daylight, the plasma levels of melatonin did not differ significantly, oscillating between 110.2 +/- 15.8 pg.mL(-1) and 157.4 +/- 34.8 pg.mL(-1), from 8 to 16 hours. L-HTP (25 mg.kg(-1), through the intracelomic route) administered at 18 hours lessened significantly the nocturnal increase of the plasma levels of melatonin (controls, 327.3 +/- 20.1 and 315.8 +/- 20.9 pg.mL(-1) vs. 242.1 +/- 24.8 and 217.5 +/- 21 pg.mL(-1), respectively, at 20 and 24 hours, P < 0.05). The results obtained showed that the administration of LHTP reduced the nocturnal melatonin release, possibly by bringing about an increase in serotonin synthesis and synaptic release in the pineal. Therefore, the serotoninergic transmission from the raphe towards the pineal would constitute a mechanism of modulation of the synthesis and melatonin release in quails.