Human DNA polymerase η accommodates RNA for strand extension.
Ribonucleotides are the natural analogs of deoxyribonucleotides, which can be misinserted by DNA polymerases, leading to the most abundant DNA lesions in genomes. During replication, DNA polymerases tolerate patches of ribonucleotides on the parental strands to different extents. The majority of human DNA polymerases have been reported to misinsert ribonucleotides into genomes. However, only PrimPol, DNA polymerase α, telomerase, and the mitochondrial human DNA polymerase (hpol) γ have been shown to tolerate an entire RNA strand. Y-family hpol η is known for translesion synthesis opposite the UV-induced DNA lesion cyclobutane pyrimidine dimer and was recently found to incorporate ribonucleotides into DNA. Here, we report that hpol η is able to bind DNA/DNA, RNA/DNA, and DNA/RNA duplexes with similar affinities. In addition, hpol η, as well as another Y-family DNA polymerase, hpol κ, accommodates RNA as one of the two strands during primer extension, mainly by inserting dNMPs opposite unmodified templates or DNA lesions, such as 8-oxo-2'-deoxyguanosine or cyclobutane pyrimidine dimer, even in the presence of an equal amount of the DNA/DNA substrate. The discovery of this RNA-accommodating ability of hpol η redefines the traditional concept of human DNA polymerases and indicates potential new functions of hpol η in vivo.


Early medicine and surgery in Calgary.
The medical history of the Calgary area can be divided into three periods: the early period before the coming of the North West Mounted Police in 1874, the middle period from 1875 to 1905, during which Fort Calgary was built and the first surgeons settled in the West, and the third period from 1905 to the present. George Alexander Kennedy was the first surgeon of the middle period. He encouraged proper sanitation, fresh air, and avoidance of cold, damp and dirt. He recommended special treatment for various systemic diseases, used chloroform in October 1880 and was known to have treated skull fractures, extradural hemorrhages, prostatic obstruction, postabortion hemorrhage, ascites and pleural effusion. Henderson, Brett, Lindsay, Rouleau, Lafferty and Mackid were the other six pioneer surgeons of the middle period. Mackid's son Ludwig took over his father's practice after studying in Europe and the United States. When he died in November 1975 at the age of 93, the last link with the pioneer surgeons of Calgary was broken.


Victim sensitivity and the accuracy of social judgments.
Recent theorizing on the relation between victim sensitivity and unethical behavior predicts that victim sensitivity is related to an asymmetrical focus on cues associated with untrustworthiness compared to cues associated with trustworthiness. This hypothesis and its consequences for the accuracy of social predictions are investigated in this article. In Study 1, participants rated the trustworthiness of 35 computer-animated faces that differed in their emotional expression. People high in victim sensitivity rated neutral and hostile faces more untrustworthy than people low in victim sensitivity, whereas no such effect was found for friendly faces. In Study 2, participants predicted the cooperativeness of 56 targets on the basis of minimal information. The accuracy of predictions was negatively related to victim sensitivity, and people high in victim sensitivity systematically underestimated targets' cooperativeness. Thus, the asymmetrical focus on untrustworthiness cues among victim-sensitive individuals seems to impair rather than improve their social judgments.


Differentiating wide complex tachycardias.
Wide complex tachycardias are cardiac rhythm disorders with three or more consecutive beats, rates exceeding 100 beats per minute and a QRS duration of 120 msec (0.12 second) or greater. The width of the QRS complex should be verified in a number of leads, since the QRS complex often appears mistakenly narrower (i.e., a QRS duration of less than 120 msec) in one or two of the 12 leads. Most wide complex tachycardias are ventricular tachycardia, and they are managed with antiarrhythmic drugs and correction of serum potassium and magnesium levels. Electrical cardioversion/defibrillation may be used in patients with serious cardiac compromise. Supraventricular tachycardias occur with or without ventricular conduction abnormalities. The management of supraventricular tachycardia requires careful evaluation for aberrant ventricular conduction or preexcitation. The cause of a wide complex tachycardia must be identified, because certain therapies can result in potentially fatal arrhythmias. If the cause cannot be determined, a test dose of intravenous adenosine can be used. Another approach is intravenous administration of procainamide and a beta-adrenergic blocker.


Spectral imaging and nucleic acid mimics fluorescence in situ hybridization (SI-NAM-FISH) for multiplex detection of clinical pathogens.
The application of nucleic acid mimics (NAMs), such as locked nucleic acid (LNA) and 2'-O-methyl-RNA (2'OMe), has improved the performance of fluorescence in situ hybridization (FISH) methods for the detection/location of clinical pathogens since they provide design versatility and thermodynamic control. However, an important limitation of FISH techniques is the low number of distinguishable targets. The use of filters in fluorescence image acquisition limits the number of fluorochromes that can be simultaneously differentiated. Recent advances in fluorescence spectral image acquisition have allowed the unambiguous identification of several microorganisms in a single sample. In this work, we aimed to combine NAM-FISH and spectral image analysis to develop and validate a new FISH variant, the spectral imaging-NAM-FISH (SI-NAM-FISH), that allows a multiplexed, robust and rapid detection of clinical pathogens. In the first stage, to implement/validate the method, we have selected seven fluorochromes with distinct spectral properties and seven bacterial species (Pseudomonas aeruginosa, Citrobacter freundii, Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter calcoaceticus). As a strong variation in fluorescence intensities is found between species and between fluorochromes, seven versions of a EUB LNA/2'OMe probe, each conjugated to one of seven fluorochromes, were used to rank species/fluorochromes by FISH and then optimize species/fluorochrome pairing. Then, final validation tests were performed using mixed populations to evaluate the potential of the technique for separating/quantifying the different targets. Overall, validation tests with different proportions of bacteria labeled with the respective fluorochrome have shown the ability of the method to correctly distinguish the species.


Length of pregnancy in African Americans: validation of a new predictive rule.
This study evaluated whether a new predictive rule is more accurate for estimating the length of pregnancy in African Americans than Nägele's rule, the accepted standard. After identifying women in early pregnancy, telephone interviews were conducted to obtain information about 16 previously established determinants of gestational length. Based on these data, a linear multivariate regression model was used to predict an estimated delivery date (EDD) for each mother. In addition, the EDD was determined using Nägele's rule. Later, the actual delivery date was compared with the EDD predicted by the new rule and with the EDD predicted by Nägele's rule. Each pregnancy was assigned to its better prediction group, either the new rule's group or the Nägele's rule group. Fifty-seven pregnancies were identified prospectively and monitored. The new rule predicted the actual delivery date more accurately in 66% (37/56) of pregnancies, Nägele's rule was a better predictor in 34% (19/56) of pregnancies, and both rules were equally accurate in predicting the delivery date for one pregnancy. The new rule was more precise than Nägele's rule (P = .022) when the binomial distribution was used. When using the linear regression model rule, a more accurate EDD can be determined for African-American women. Moreover, it is possible to predict the risk of preterm delivery (those occurring > 3 weeks earlier than the EDD).


Investigation of viable taxa in the deep terrestrial biosphere suggests high rates of nutrient recycling.
The deep biosphere is the largest 'bioreactor' on earth, and microbes inhabiting this biome profoundly influence global nutrient and energy cycles. An important question for deep biosphere microbiology is whether or not specific populations are viable. To address this, we used quantitative PCR and high throughput 16S rRNA gene sequencing of total and viable cells (i.e. with an intact cellular membrane) from three groundwaters with different ages and chemical constituents. There were no statistically significant differences in 16S rRNA gene abundances and microbial diversity between total and viable communities. This suggests that populations were adapted to prevailing oligotrophic conditions and that non-viable cells are rapidly degraded and recycled into new biomass. With higher concentrations of organic carbon, the modern marine and undefined mixed waters hosted a community with a larger range of predicted growth strategies than the ultra-oligotrophic old saline water. These strategies included fermentative and potentially symbiotic lifestyles by candidate phyla that typically have streamlined genomes. In contrast, the old saline waters had more 16S rRNA gene sequences in previously cultured lineages able to oxidize hydrogen and fix carbon dioxide. This matches the paradigm of a hydrogen and carbon dioxide-fed chemolithoautotrophic deep biosphere.


Lost in Translation? Care Coordination Across Contexts in Swedish Homecare Nursing.
The responsibilities for delivery of care in Sweden is divided between the regions and the municipalities. The regions run the hospitals and the primary care centres (PCCs) whereas the municipalities are responsible for homecare nursing and nursing homes. The homecare nurses and the doctors they need to seek advice from, thus belong to different organizations/contexts. As more patients with multi- and long-term illnesses are taken care of in their homes the workload of the homecare nurses has increased. A new healthcare agreement has thus been signed between a region in South Sweden and its municipalities. The healthcare agreement states that doctors from the PCCs are to form mobile teams together with the homecare nurses. This paper reports from a pre-study investigating how the agreement, in terms of translation sociology, is interpreted in four of the municipalities. The aim of the research project as a whole is to develop digital support systems for the mobile teams.


Intensity, Duration, and Location of High-Definition Transcranial Direct Current Stimulation for Tinnitus Relief.
Tinnitus is the perception of a phantom sound. The aim of this study was to compare current intensity (center anode 1 mA and 2 mA), duration (10 minutes and 20 minutes), and location (left temporoparietal area [LTA] and dorsolateral prefrontal cortex [DLPFC]) using 4 × 1 high-definition transcranial direct current stimulation (HD-tDCS) for tinnitus reduction. Twenty-seven participants with chronic tinnitus (>2 years) and mean age of 53.5 years underwent 2 sessions of HD-tDCS of the LTA and DLPFC in a randomized order with a 1 week gap between site of stimulation. During each session, a combination of 4 different settings were used in increasing dose (1 mA, 10 minutes; 1 mA, 20 minutes; 2 mA, 10 minutes; and 2 mA, 20 minutes). The impact of different settings on tinnitus loudness and annoyance was documented. Twenty-one participants (77.78%) reported a minimum of 1 point reduction on tinnitus loudness or annoyance scales. There were significant changes in loudness and annoyance for duration of stimulation,F(1, 26) = 10.08,P< .005, and current intensity,F(1, 26) = 14.24,P= .001. There was no interaction between the location, intensity, and duration of stimulation. Higher intensity (2 mA) and longer duration (20 minutes) of stimulation were more effective. A current intensity of 2 mA for 20-minute duration was the most effective setting used for tinnitus relief. The stimulation of the LTA and DLPFC were equally effective for suppressing tinnitus loudness and annoyance.


Comparative Risks of Aldehyde Constituents in Cigarette Smoke Using Transient Computational Fluid Dynamics/Physiologically Based Pharmacokinetic Models of the Rat and Human Respiratory Tracts.
Computational fluid dynamics (CFD) modeling is well suited for addressing species-specific anatomy and physiology in calculating respiratory tissue exposures to inhaled materials. In this study, we overcame prior CFD model limitations to demonstrate the importance of realistic, transient breathing patterns for predicting site-specific tissue dose. Specifically, extended airway CFD models of the rat and human were coupled with airway region-specific physiologically based pharmacokinetic (PBPK) tissue models to describe the kinetics of 3 reactive constituents of cigarette smoke: acrolein, acetaldehyde and formaldehyde. Simulations of aldehyde no-observed-adverse-effect levels for nasal toxicity in the rat were conducted until breath-by-breath tissue concentration profiles reached steady state. Human oral breathing simulations were conducted using representative aldehyde yields from cigarette smoke, measured puff ventilation profiles and numbers of cigarettes smoked per day. As with prior steady-state CFD/PBPK simulations, the anterior respiratory nasal epithelial tissues received the greatest initial uptake rates for each aldehyde in the rat. However, integrated time- and tissue depth-dependent area under the curve (AUC) concentrations were typically greater in the anterior dorsal olfactory epithelium using the more realistic transient breathing profiles. For human simulations, oral and laryngeal tissues received the highest local tissue dose with greater penetration to pulmonary tissues than predicted in the rat. Based upon lifetime average daily dose comparisons of tissue hot-spot AUCs (top 2.5% of surface area-normalized AUCs in each region) and numbers of cigarettes smoked/day, the order of concern for human exposures was acrolein > formaldehyde > acetaldehyde even though acetaldehyde yields were 10-fold greater than formaldehyde and acrolein.


Physicochemical and ion-binding properties of highly aliphatic humic substances extracted from deep sedimentary groundwater.
Humic substances (HSs) are ubiquitous in various aquatic systems and play important roles in many geochemical processes. There is increasing evidence of the presence of HSs in deep groundwater; nevertheless, their ion binding properties are largely unknown. In this study we investigated the physicochemical and ion-binding properties of humic and fulvic acids extracted from deep sedimentary groundwater. The binding isotherms of protons (H(+)) and copper (Cu(2+)) were measured by potentiometry and fitted to the NICA-Donnan model, and the obtained parameters were compared with the generic parameters of the model, which are the average parameters for HSs from surface environments. The deep groundwater HSs were different from surface HSs, having high aliphaticities, high sulfur contents, and small molecular sizes. Their amounts of acidic functional groups were comparable to or slightly larger than those of surface HSs; however, the magnitude of Cu(2+) binding to the deep groundwater HSs was smaller. The NICA-Donnan model attributed this to the binding of Cu(2+) to chemically homogeneous low affinity sites, which presumably consist of carboxylic groups, via mono-dentate coordination at relatively low pH. The binding mode tended to shift to multi-dentate coordination with carboxylic groups and more heterogeneous alcoholic/phenolic groups at higher pH. X-ray absorption spectroscopy also revealed that Cu(2+) binds to O/N containing functional groups and to a lesser extent S containing functional groups as its divalent from. This study shows the particularity of the deep groundwater HSs in terms of their physicochemical and ion-binding properties, compared with surface HSs.


[Diagnostic imaging within the scope of lung transplantation].
Recent progress in both surgical techniques and therapeutic medication of immunosupression have made lung transplantation a promising option for patients with untreatable diseases of the lung parenchyma. Because preoperatively and postoperatively diagnostic imaging has crucial importance for patient management and clinical decision making we aim to describe imaging features of frequent pathologies in patients after lung transplantation. We reviewed radiological examinations of patients after lung transplantation performed at our institution over a period of four years, and exemplary cases were selected for presentation. Our interest was focussed on both conventional and CT-imaging of postoperative alterations, infections, organ rejection, and pathologies of the airways. Moreover, post-biopsy alterations and lymphoproliferative disorders were documented. Together with clinical information we aimed to give a concise description of specific pathologic entities. Also, the diagnostic impact of more recent techniques such as spiral-CT and thin-section CT should be discussed. In cases of early postoperative pathologies and in infections conventional radiography is diagnostically reliable when interpreted together with clinical information. In cases of acute or chronic organ rejection, of lymphoproliferative disorders, of diseases of central or small airways, and for the choice of an appropriate biopsy site, CT has proved to be a valuable imaging modality. Spiral-CT allows airway volumetry in cases of strictures or dehiscence, thin-section CT enables assessment of subtle parenchymal pathologies, notably in cases of chronic organ rejection. The radiographic findings described below represent specific pathogenetic entities in lung-transplant patients (postoperative alterations, infections, posttransplant lymphoproliferative disorders). Their accurate recognition will have a positive impact on the further clinical history. In the near future, more sophisticated CT techniques should widen our pathogenetic knowledge of alterations in transplanted lungs.


[Fiberoptic bronchoscopy via laryngeal mask in children].
A fiberoptic bronchoscope provides a good access to the distal airways, inaccessible for a rigid bronchoscope. A major disadvantage of the fiberoptic bronchoscope in tracheal intubation of children is its little diameter, impeding the instrumentation and suction. A laryngeal mask (LM) of a suitable size was used with the fiberoptic bronchoscope in 68 children aged 0 to 15 years under TIVA. A large-sized fiberoptic bronchoscope with a channel for instruments can be safely and effectively used in anesthesized children due to LM. A relatively large internal diameter of LM permits ventilation round the fiberoptic bronchoscope. The method is atraumatic and represents a good alternative to the rigid bronchoscope in children.


Transmission probabilities of HIV and herpes simplex virus type 2, effect of male circumcision and interaction: a longitudinal study in a township of South Africa.
A synergy between HIV and herpes simplex virus type 2 (HSV-2) infections has been reported in observational studies. The objectives of this study were to estimate the per-sex-act female-to-male transmission probabilities (FtoMTPs) of HIV and HSV-2, the effect of each infection on the FtoMTP of the other and the effect of male circumcision on these FtoMTPs. We used longitudinal data collected during the male circumcision trial conducted in Orange Farm (South Africa). Results were obtained by specific mathematical modeling of HIV and HSV-2 statuses of the men as functions of their sexual behavior and male circumcision status. The model took into account an estimation of the HIV and HSV-2 statuses of each of their female partners. Confidence intervals (CI) were estimated using a bootstrap resampling method. The HIV and HSV-2 FtoMTPs, during an unprotected sexual contact for an uncircumcised male in the absence of the other virus in both partners, were 0.0047 (95% CI: 0.0014-0.017) and 0.0067 (95% CI: 0.0028-0.014), respectively. HSV-2 in either partner increased HIV FtoMTP with a relative risk (RR) of 3.0 (95% CI: 1.01-7.3). Conversely, HIV in either partner increased HSV-2 FtoMTP (RR= 2.5; 95% CI: 1.1- 6.3). Male circumcision significantly decreased these probabilities with RRs of 0.24 (95% CI: 0.11-0.44) and 0.59 (95% CI: 0.36-0.91), respectively. This study gave the first estimates of HSV-2 per-sex-act FtoMTPs in Africa. It demonstrated a synergy between HIV and HSV-2 infections and a protective effect of male circumcision on HSV-2 acquisition by males.


Melatonin reverses depressive and anxiety like-behaviours induced by diabetes: involvement of oxidative stress, age, rage and S100B levels in the hippocampus and prefrontal cortex of rats.
Diabetes is associated with depression and anxiety symptoms. The current investigation was designed to explore the effect of melatonin on depressive and anxiety like-behaviours, oxidative stress, levels of AGE, RAGE and S100B in streptozotocin-induced diabetic rats. The animals were divided into four groups: Normoglycemic; Normoglycemic + melatonin; diabetic; diabetic + melatonin (10 mg/kg, for 4 weeks). The malondialdehyde (MDA), reduced glutathione (GSH), AGE, RAGE and S100B were measured and the depressive and anxiety like-behaviours were assessed by forced swimming and elevated plus maze tests, respectively. Melatonin ameliorates depressive and anxiety like-behaviours. Concomitantly, melatonin reversed diabetes induced increase of MDA, AGE and decrease of GSH and S100B levels in the hippocampus and prefrontal cortex. In conclusion, our results showed that melatonin administration may exert antidepressant-like and anxiolytic effects in diabetic rats through normalising of AGE/RAGE, S100B and oxidative stress in the prefrontal cortex and hippocampus.


[Surgical treatment of alkaline gastritis].
A method for reconstructive operation on the stomach with formation of a Y-shaped anastomosis in patients with alkaline gastritis is discussed. The author suggests that the an area of the mesentery with the least number of vessels should be chosen between the vascular arcade and two arteries of the jejunum (at a distance of 12-15 cm from the ligament of Treitz) and then dividing the mesentery parallel and medial to the vascular arch. Maximal maintenance of blood supply and innervation of the loop isolated after Roux ensured good operative results in 84 patients.


Clinical significance of quantitative categorization of HER2 fluorescent in situ hybridization results in invasive breast cancer patients treated with HER2-targeted agents.
HER2 (ERBB2) gene status serves as a strong predictive marker of response to HER2-targeted agents in invasive breast cancers, albeit with heterogeneous response. Our aim was to determine the distribution and prognosis of HER2 groups by fluorescent in situ hybridization (FISH) using the updated 2018 American Society of Clinical Oncology-College of American Pathologist (ASCO-CAP) guidelines. We identified 226 cases of equivocal or positive HER2 FISH invasive breast cancer (interpreted by ASCO-CAP guidelines at the time of reporting) who received HER2-targeted agents from 2006 to 2017. We subcategorized Group 1 further into three subgroups: low amplified (HER2/CEP17 ratio ≥ 2.0-2.99, mean HER2/cell 4.0-5.9), amplified (HER2/CEP17 ratio ≥ 2.0-2.99, mean HER2/cell ≥ 6), and excessive amplification (HER2/CEP17 ratio ≥ 3.0, mean HER2/cell ≥ 4.0). Outcomes studied were recurrence, metastasis, second breast primary, disease-specific survival (DSS), and overall survival (OS). Univariate analysis showed that the five categories of HER2 FISH were significantly associated with OS (p < 0.01), specifically higher HER2 amplification was associated with fewer deaths. HER2 FISH status also statistically significantly relates to DFS (p < 0.01) and metastasis (p = 0.01) but not with recurrence or second breast primary in our study. Tumor type and HER2 ISH Groups are independent predictors for both OS and DFS in our cohort. The proposed Group 1 subcategories were significantly associated with OS (p < 0.01) and DFS (p < 0.01), excessive HER2 amplification was associated with longer median survival. The Cox regression models showed better survival outcomes for the excessive amplification subgroup than the low amplified subgroup, with OS (hazard ratio = 0.63, 95% CI 0.42-0.93) and DFS (HR = 0.55, 95% CI 0.37-0.83). We demonstrated that in HER2 FISH Group 1 patients, high HER2 amplification was significantly associated with longer OS and DFS; these patients seem to benefit more from HER2-targeted regimens. We recommend reporting these Group 1 subcategories when assessing HER2 FISH.


Rearranged Homoadamantane-Type Polycyclic Polyprenylated Acylphloroglucinols from Hypericum pseudohenryi.
Hypseudohenones A-C (1-3), the first rearranged homoadamantane-type polycyclic polyprenylated acylphloroglucinols, were isolated from Hypericum pseudohenryi. Their structures with an unprecedented tricyclo[184.108.40.206,8]undecane-2,4,10-trione core were determined by spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A method for determining the relative configuration at C-3 was established by the peak shape of H-28 or J-value of H-3/H-28. Moreover, 2-3 exhibited significant AChE inhibitory activity, and the interactions of 2-3 with AChE were evaluated by molecular docking.


A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult Drosophila.
A screen for neuroprotective genes in Drosophila melanogaster led to the identification of a mutation that causes extreme, progressive loss of adult brain neuropil in conjunction with massive brain overgrowth. We mapped the mutation to the brain tumor (brat) locus, which encodes a tripartite motif-NCL-1, HT2A, and LIN-41 (TRIM-NHL) RNA-binding protein with established roles limiting stem cell proliferation in developing brain and ovary. However, a neuroprotective role for brat in the adult Drosophila brain has not been described previously. The new allele, bratcheesehead (bratchs ), carries a mutation in the coiled-coil domain of the TRIM motif, and is temperature-sensitive. We demonstrate that mRNA and protein levels of neural stem cell genes are increased in heads of adult bratchs mutants and that the over-proliferation phenotype initiates prior to adult eclosion. We also report that disruption of an uncharacterized gene coding for a presumptive prolyl-4-hydroxylase strongly enhances the over-proliferation and neurodegeneration phenotypes. Together, our results reveal an unexpected role for brat that could be relevant to human cancer and neurodegenerative diseases.


Erratum.
May I point out a confusing error that occurs in the last line of Table 1 in our recent short paper (H. H. Plough and Madelon R. Grimm, "Reversal to Penicillin Sensitivity in a Cysteine-requiring Mutant of Salmonella," Science, February 18, 1949, pp. 173-4). This should read: "S. D. alone- - - - - - -," that is, seven minus signs instead of one minus and six plus signs. I had to correct in galley an error of the original manuscript under a similar heading five lines above, and I assume that somehow the last line got shifted too.


The Remission Clinic approach to halt the progression of kidney disease.
Randomized multicenter studies in diabetic and nondiabetic patients with chronic proteinuric nephropathies have clearly demonstrated that renin-angiotensin system (RAS) inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) used alone or in combination, effectively retard renal disease progression. Proteinuria reduction, in addition to arterial blood pressure control, largely mediates the nephroprotective effect of RAS inhibitor therapy. Despite RAS inhibition, however, most patients with chronic kidney disease (CKD) progress to end-stage renal disease (ESRD). This highlights the importance of innovative therapies to halt or revert CKD progression in those at risk. Along this line, a multimodal strategy (Remission Clinic) targeting urinary proteins by dual RAS inhibition with ACE inhibitors and ARBs up-titrated to maximum tolerated doses, by intensified blood pressure control, amelioration of dyslipidemia by statins, smoking cessation and healthy lifestyle implementation was safely and effectively applied at our outpatient clinic to normalize urinary proteins and prevent renal function loss in patients otherwise predicted to rapidly progress to ESRD because of nephrotic-range proteinuria refractory to standard antihypertensive dosages of an ACE inhibitor. This approach achieved remission or regression of proteinuria and stabilized kidney function in most cases, and almost fully prevented progression to ESRD. Provided patients are closely monitored and treatment is cautiously up-titrated according to tolerability, this approach might be safely applied in day-by-day hospital practice. Effective prevention of ESRD would reduce costs of renal replacement therapy by dialysis or transplantation and would be life-saving where these are not available for all patients in need.


A facile synthesis of fluorescent silver nanoclusters with human ferritin as a synthetic and interfacing ligand.
Water-soluble fluorescent silver nanoclusters (NCs) formed on biomolecule ligands have been extensively studied due to their great potential as new biocompatible fluorescent materials for biosensors. As synthetic ligands, proteins in particular can provide unique structures and functions to the assembled fluorescent silver clusters. A key challenge, however, is to develop appropriate protein ligands and synthetic approaches for cluster formation, especially using native aqueous solutions, to fully preserve the valuable properties of the protein templates. Here we report a human ferritin-templated synthesis of fluorescent silver NCs under neutral aqueous buffer conditions. The unique metal binding property of ferritin and an optimized silver ion reduction allowed us to produce highly stable fluorescent silver NCs that are steadily assembled in the cage-like ferritin proteins. The fluorescent clusters were also successfully assembled on genetically engineered ferritin with antibody-binding protein G. The resulting protein G-ferritin-silver NC complex fully retained the ferritin structure as well as the antibody binding ability. The present silver nanoclusters on ferritin (Ft-Ag NCs) also showed highly specific Cu(2+)-induced fluorescence quenching. By exploiting the large but stable nature of ferritin, we fabricated a highly robust and porous hydrogel sensor system for rapid Cu(2+) detection, where the Ft-Ag NCs were stably encapsulated in surface-bound hydrogels with large pore sizes. Our Ft-Ag NCs that are formed under native aqueous conditions will have great potential as a new fluorescent material with the high structural and functional diversities of ferritin.


NT-proBNP and Its Correlation with In-Hospital Mortality in the Very Elderly without an Admission Diagnosis of Heart Failure.
The diagnosis of heart failure (HF) is often difficult and underestimated in very elderly comorbid patients, especially when an echocardiographic evaluation is not available or feasible. to evaluate NT-proBNP values and their correlation with in-hospital mortality in a population of very elderly hospitalized for medical conditions other than HF. We performed a prospective observational study on 403 very elderly admitted to an Internal Medicine and Geriatrics Department. Exclusion criterion was an admission diagnosis of HF. Patients with at least one symptom or sign compatible with HF were tested for NT-proBNP. NT-proBNP values < 300 pg/ml were considered as an age-independent exclusion criterion for HF (high negative predictive value), while NT-proBNP values ≥ 1800 pg/ml were considered as a diagnostic criterion. Main comorbidities and laboratory parameters were considered to adjust regression analyses between NT-proBNP and in-hospital mortality. NT-proBNP values ≥ 1800 pg/ml were present in 61.0% of patients and 32.8% of patients laid between 300 ≤ NT-proBNP < 1800 pg/ml values. NT-proBNP values were associated with the main indices of disease severity/organ failure considered such as reduced eGFR, reduced albumin and elevated CRP. NT-proBNP values ≥ 1800 pg/ml and ln(NT-proBNP) values were significantly associated with in-hospital mortality independently from the main comorbidities and lab parameters considered. The patients, who were already taking ACE inhibitors/Angiotensin Receptor Blockers before admission, showed lower in-hospital mortality. Testing for NT-proBNP should be strongly recommended in the hospitalized very elderly, because of the very high prevalence of underlying HF and its impact on in-hospital mortality, to identify an underlying cardiac involvement that requires appropriate treatment.


Hormonal changes in postmenopausal women with breast cancer treated with trilostane and dexamethasone.
Postmenopausal women with metastatic breast cancer were treated with trilostane, initially 240 mg daily increasing after 3 days to 480 mg daily and after a further three days to 960 mg daily. After 3 days at this dose dexamethasone 1 mg daily was added and this combination was continued until disease progression occurred. Partial remission was seen in 26% and stabilization of previously progressive disease in a further 13% of the first twenty-three patients studied. During therapy with trilostane alone significant increases in DHEAS, androstenedione, 17-hydroxypregnenolone, progesterone, testosterone and oestradiol were seen. A significant fall in oestrone concentration occurred at the same time. After dexamethasone was added the elevated steroid concentrations fell back to the baseline while oestrone remained depressed below this and testosterone was also significantly lowered. No change was seen in cortisol or ACTH concentration while patients were on trilostane alone but cortisol levels were undetectable after dexamethasone was added though, in most patients, ACTH remained detectable. There was no change in the ratio of delta 5:delta 4 steroids at any stage of therapy but a highly significant increase in the androstenedione: oestrone ratio was seen. We conclude that in long-term use in vivo it is difficult to demonstrate that trilostane inhibits 3 beta-hydroxysteroid dehydrogenase but it may produce inhibition of aromatase.


Between hope and abandonment: black queer collectivity and the affective labour of biomedicalised HIV prevention.
This paper investigates how current transformations in HIV prevention in the USA are intensifying a logic of viral containment rooted in biomedicine and behavioural science, in order to curb the recent rise in new HIV infections, predominantly among young African-American 'men who have sex with men'. Based on fieldwork in Baltimore, I examine how this paradigm shift is translated into concrete prevention activities that focus on HIV testing and treatment. By attending to the affective labour performed by members of Baltimore's Ballroom scene - a kinship system of black queer youth structured around competitive dance and performance - I show how the emergent 'Test & Treat' approach becomes a polyvalent object that attracts a host of optimistic investments in collective and individual prosperity, which nevertheless threaten to remain unrequited. Finally, I argue that the current move towards a biomedically mediated model of viral management depoliticises the struggle against HIV by suggesting that we can treat our way out of an epidemic that in fact remains intricately interwoven with racialised violence against the queer, the poor and the otherwise dispossessed.


Sustained Cortical and Subcortical Measures of Auditory and Visual Plasticity following Short-Term Perceptual Learning.
Short-term training can lead to improvements in behavioral discrimination of auditory and visual stimuli, as well as enhanced EEG responses to those stimuli. In the auditory domain, fluency with tonal languages and musical training has been associated with long-term cortical and subcortical plasticity, but less is known about the effects of shorter-term training. This study combined electroencephalography (EEG) and behavioral measures to investigate short-term learning and neural plasticity in both auditory and visual domains. Forty adult participants were divided into four groups. Three groups trained on one of three tasks, involving discrimination of auditory fundamental frequency (F0), auditory amplitude modulation rate (AM), or visual orientation (VIS). The fourth (control) group received no training. Pre- and post-training tests, as well as retention tests 30 days after training, involved behavioral discrimination thresholds, steady-state visually evoked potentials (SSVEP) to the flicker frequencies of visual stimuli, and auditory envelope-following responses simultaneously evoked and measured in response to rapid stimulus F0 (EFR), thought to reflect subcortical generators, and slow amplitude modulation (ASSR), thought to reflect cortical generators. Enhancement of the ASSR was observed in both auditory-trained groups, not specific to the AM-trained group, whereas enhancement of the SSVEP was found only in the visually-trained group. No evidence was found for changes in the EFR. The results suggest that some aspects of neural plasticity can develop rapidly and may generalize across tasks but not across modalities. Behaviorally, the pattern of learning was complex, with significant cross-task and cross-modal learning effects.


So Many Roads: the Multifaceted Regulation of Autophagy Induction.
Autophagy is an evolutionary conserved, degradative process from single-cell eukaryotes, such as Saccharomyces cerevisiae, to higher mammals, such as humans. The regulation of autophagy has been elucidated through the combined study of yeast, Caenorhabditis elegans, mice, Drosophila melanogaster, and humans. MTOR, the major negative regulator of autophagy, and activating nutrient kinases, such as 5'-AMP-activated protein kinase (AMPK), interact with the autophagy regulatory complex: ULK1/2, RB1CC1, ATG13, and ATG101. The ULK1/2 complex induces autophagy by phosphorylating downstream autophagy complexes, such as the BECN1 PIK3 signaling complex that leads to the creation of LC3+ autophagosomes. We highlight in this review various reports of autophagy induction that are independent of these regulators. We discuss reports of MTOR-independent, AMPK-independent, ULK1/2-independent, and BECN1-PIK3C3-independent autophagy. We illustrate that autophagy induction and the components required vary by the nature of the induction signal and type of cell and do not always require canonical members of the autophagy signaling pathway. We illustrate that rather than thinking of autophagy as a linear pathway, it is better to think of autophagy induction as an interconnecting web of key regulators, many of which can induce autophagy through different requirements depending on the type and length of induction signals.


The prognostic value of Ki67 in systemically untreated patients with node-negative breast cancer.
To evaluate the utility of Ki67 as a prognostic marker in a series of patients with node-negative breast cancer untreated with adjuvant systemic therapy. The cohort consisted of 203 cases treated with breast conserving surgery and radiation only; median follow-up was 183 months (range 156-277 months). An immunohistochemical panel of oestrogen receptor (ER), progesterone receptor (PR), cytokeratin (CK)5/6 and Ki67 and human epidermal growth factor 2 in situ hybridization (HER2-ISH) was performed on the tumour samples. Ki67 scores were evaluable in 193/203 patients (95.1%). The primary outcome was breast cancer specific survival (BCSS). Of the cohort, 29 (14.2%) died of breast cancer. A cut off of 10% separated tumours into a 'Ki67-low' (n=70) or 'Ki67-high' group (n=123). The breast cancer specific survival was 97.1% and 77.6% for Ki67-low and Ki67-high groups, respectively. Univariate analysis showed that in this lymph node-negative cohort, the predictors for BCSS were tumour size, Ki67, LVI, age and histological grade 3. Multivariable analysis showed that Ki67 index and lymphovascular space invasion were independent predictors of breast cancer death. To examine the utility of Ki67 in assignment of immunohistochemically molecular subtypes, cases were assigned into Luminal A (ER-positive, HER2-negative, Ki67 ≤14%), Luminal B (ER-positive, HER2-negative, Ki67 >14%) and triple negative (ER/PR-negative and HER2-negative, any Ki67). The 15-year breast cancer specific survival was 91.7%, 79.4% and 75.8%, respectively. A statistically significant difference in breast cancer specific survival is seen in groups defined using Ki67 and receptor status, whereas histological grading was not a significant predictor of survival. Ki67 immunostaining provides prognostic information beyond traditionally assessed clinicopathological variables.


Three-dimensional conformal therapy versus standard radiation therapy in localized carcinoma of prostate: an update.
This study updates technical principles and results of 3-dimensional conformal radiation therapy (3D-CRT) in localized carcinoma of the prostate. Between January 1992 and December 1999, 312 patients were treated with 3D-CRT and 135 patients were treated with bilateral arcs standard radiation therapy (SRT) alone for clinical stage T1b-c or T2 histologically confirmed prostate cancer. None of these patients received hormonal therapy. Mean follow-up for patients in the 3D-CRT group was 3.2 years (range, 2-5.9 years) and for SRT patients, 4.7 years (range, 4-7 years). For 3D-CRT, 7 intersecting fields were used (cerrobend blocking or multileaf collimation) to deliver 68-74 Gy to the prostate. Standard radiation therapy consisted of bilateral 120 degree rotational arcs, with portals using 2-cm margins around the prostate to deliver 68-70 Gy to the prostate. The criterion for chemical disease-free survival was a postirradiation prostate-specific antigen (PSA) value following the American Society for Therapeutic Radiology and Oncology guidelines. Symptoms during treatment were quantitated weekly, and late effects were assessed every 4-6 months. Dose-volume histograms showed a two-thirds reduction with 3D-CRT in normal bladder or rectum receiving > or = 70 Gy with 3D-CRT. Higher 5-year chemical disease-free survival was observed with 3D-CRT (75%; for T1b-c and 79%; for T2 tumors) compared with SRT (61% and 65%, P = 0.01 and P = 0.12, respectively). There was no statistically significant difference in chemical disease-free survival in patients with Gleason score of < or = 4 (P = 0.85), but, with Gleason score of 5-7, the 5-year survival rates were 83% with 3D-CRT and 59% with SRT (P < or = 0.01). In 245 patients with pretreatment PSA of < or = 10 ng/mL treated with 3D-CRT, the chemical disease-free rate was 80% versus 72% in 98 patients treated with SRT (P = 0.21). In patients with PSA of 10.1-20 ng/mL, the chemical disease-free survival rate for 50 patients treated with 3D-CRT was 71% compared with 43% for 20 patients treated with SRT (P = 0.02). The corresponding values were 59% and 16%, respectively, for patients with PSA levels > 20 ng/mL (P = 0.09). On multivariate analysis, the most important prognostic factors for chemical failure were pretreatment PSA (P = 0.004), nadir PSA (P = 0.001), and 3D-CRT technique (P = 0.012). Moderate dysuria was reported by 2%-5% of patients treated with 3D-CRT in contrast to 6%-9% of patients treated with SRT. The incidence of moderate loose stools or diarrhea, usually after the fourth week of treatment, was 3%-5% in the 3D-CRT patients and 8%-19% in the SRT group. Late intestinal grade 2 morbidity (proctitis or rectal bleeding) was 1% in the 3D-CRT group in contrast to 7% in SRT patients. The 3D-CRT spares more normal tissues, yields higher chemical disease-free survival, and results in less treatment morbidity than SRT in treatment of stage T1-T2 prostate cancer. Follow-up at > or = 10 years is needed to confirm these observations.


[Sturge-Weber syndrome revisited. Evaluation of encephalic morphological changes with computerized tomography and magnetic resonance].
Sturge-Weber Syndrome (SWS) is characterized by facial flammeus nevus, leptomeningeal angiomatosis and coroidal hemangioma and MRI and CT scans are used to disclose the angiomatosis and secondary brain lesions. We review the CT and/or MRI scan of 26 patients with SWS. In 75% of cases the SWS was unilateral and in 25% bilateral, being the angiomatosis more frequent on occipital lobe (93%) than on the parietal (83%), frontal (53%) and temporal (53%) lobe. Diencephalon was involved in 13%, midbrain in 6% and cerebellum in 6% of cases. Other imaging features were: calcifications (88%), brain atrophy (85%), coroidal plexuses hypertrophy (72%), medullar veins enlargement (61%), ocular coroidal enhancement (20%). MRI was superior in depicting all morphological abnormalities of SWS, but calcifications. MRI is the best imaging method to evaluate morphologically the SWS, being useful to confirm the diagnosis and establish the extension of the disease.


A23187: a calcium ionophore that directly increases cardiac contractility (38704).
The effect of the calcium ionophore A23187 on contractility in guinea pig left atria was studied. This ionophore increased both the force of contraction and the rate of tension development in a concentration dependent manner. The positive inotropic effect of A23187 is not mediated by activation of beta-receptors or by the release of endogenous catecholamines since neither propranolol nor pretreatment with reserpine altered the inotropic effect of this agent. Our studies of the dependence of contractile force on external calcium indicate that A23187 enhances the response of atrial muscle to external calcium ions. Since A23187 is known to facilitate the movement of calcium across biological membranes, we believe the ionophore may be acting either by increasing calcium influx across the myocardial cell membrane or by facilitating calcium release from sarcoplasmic reticulum.


Echinococcus granulosus genotypes in Iran: a systematic review.
Cystic echinococcosis (CE) caused by Echinococcus granulosus sensu lato (s.l.) is a significant zoonosis, especially in developing countries of the Middle East, with many studies focusing on CE genotypes in Iran. We performed a systematic review to determine the exact status of E. granulosus genotypes in the country. We explored English (Pubmed, Scopus, ISI Web of Science and Science Direct) and Persian (Magiran, Iran Medex and Scientific Information Database) databases along with Google Scholar. Our review included 73 studies published prior to the end of 2015. In total, 2952 animal (intermediate and definitive) hosts were examined, and the prevalent genotypes comprised G1 (92.75%) and G6 (4.53%) in sheep, cattle, camels, goats and buffaloes; G3 (2.43%) in five herbivore hosts and dogs; G7 (0.2%) in sheep and goats; and G2 (0.06%) in dogs. G1 was mostly dominant in West Azerbaijan, whereas G3 and G6 were identified most frequently in the provinces of Isfahan and Fars, respectively. Regarding human CE infection, 340 cases were reported from Iran, with the identified genotypes G1 (n = 320), G6 (n = 13) and G3 (n = 7). Most CE-infected humans originated from Isfahan province (168 cases), whereas the lowest number of infected persons was noted in Kerman province (two cases). The information obtained from this systematic review is central to better understanding the biological and epidemiological characteristics of E. granulosus s.l. genotypes in Iran, leading to more comprehensive control strategies.


Solubilization and purification of a putative quisqualate-sensitive glutamate receptor from crustacean muscle.
Two high-affinity glutamate-binding proteins have been solubilized and purified from crustacean muscle membranes. L-[3H]Glutamate binding to intact membranes gave IC50 values (concn. giving 50% inhibition) of 0.35 microM for glutamate. 9.0 microM for quisqualate and 36.2 microM for ibotenic acid. Kainate, domoate, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, D-glutamate and L-aspartate were poor inhibitors of glutamate binding. The two protein were purified approx. 600-fold from muscle membranes by use of concanavalin A and gel-filtration column chromatography. One protein showed an apparent Stokes radius of 5.4 nm, as determined by gel filtration, with a subunit of Mr 74000 as shown by SDS/polyacrylamide-gel electrophoresis. Analysis of glutamate binding to this protein revealed a KD of 2.4 microM and a Bmax, of 15.5 nmol/mg, and a k1 for quisqualate inhibition of glutamate binding of 1.0 microM. The second protein was eluted anomalously from the gel-filtration column and showed a subunit of Mr 65000 on SDS/polyacrylamide gels. Glutamate binding to this protein showed a KD of 1.3 microM and a Bmax, of 14.5 nmol/mg, and was only slightly sensitive to the presence of quisqualate (Ki = 0.8 mM). Glutamate binding to both proteins was insensitive to kainate. It is concluded that the Mr-74000 protein is a prime candidate for the quisqualate-sensitive receptor of the crustacean neuromuscular junction.


Genetic diversity and haplotypes of Echinococcus granulosus isolated from cattle and buffaloes and first report of E. ortleppi (G5) in buffaloes in Pakistan based on mitochondrial cytochrome c oxidase subunit-1 gene (mt-CO1) markers.
Cystic echinococcosis (CE) is a parasitic disease that is caused by larval stage of Echinococcus granulosus tapeworm, one of the most important and neglected zoonotic disease. Although the echinococcosis is endemic in the neighboring countries, information regarding circulating genotypes of E. granulosus sensu lato is scarce in Pakistan. Therefore, the main purpose of this report was to contribute in molecular epidemiology and to find genetic variation and haplotypes of E. granulosus s.l. in cattle and buffalo isolates. To identify species circulating in country, parasite samples were collected from different slaughterhouses and butcher shops of two major cities, Rawalpindi and Peshawar located in Punjab and Khyber Pakhtunkhwa (KP) provinces, Pakistan, respectively. A total of 100 CE cyst samples were investigated from buffalo (n = 61), and cattle (n = 39) hosts. After genomic DNA extraction from individual cyst materials, mt-CO1 (875 bp) gene was amplified by PCR. After that, PCR products were electrophoresed on the agarose gel then purified and sequenced using forward primer. The sequences were trimmed (779 bp), aligned and matched with NCBI published sequences. E. granulosus s.s. (G1, G3) (71.4%; n = 20/28) was confirmed as the dominant species in buffalo and cattle. E. ortleppi (G5) (28.6%; n = 8/28) was recorded for the first time in both buffalo and cattle isolates from Rawalpindi. E. granulosus s.l. haplotype network showed single predominant haplotype, which comprised 40% of population. Tajima's D and Fu's Fs were negative and significant for E. ortleppi (G5), suggesting population expansion in Pakistan. Therefore, more studies using isolates of E. granulosus s.l. from various locations and intermediate hosts across Pakistan will add new data on molecular epidemiology and genotyping for effective control strategies of CE in Pakistan.


Reduced carotid baroreceptor distensibility-induced baroreflex resetting contributes to impairment of sodium regulation in rats fed a high-fat diet.
Decreased carotid arterial compliance has been reported in obese subjects and animals. Carotid baroreceptors are located at the bifurcation of the common carotid artery, and respond to distension of the arterial wall, suggesting that higher pressure is required to obtain the same distension in obese subjects and animals. A hyperosmotic NaCl solution induces circulatory volume expansion and arterial pressure (AP) increase, which reflexively augment renal excretion. Thus, we hypothesized that sodium regulation via the baroreflex might be impaired in response to chronic hyperosmotic NaCl infusion in rats fed a high-fat diet. To examine this hypothesis, we used rats fed a high-fat (Fat) or normal (NFD) diet, and measured mean AP, water and sodium balance, and renal function in response to chronic infusion of hyperosmotic NaCl solution via a venous catheter. Furthermore, we examined arterial baroreflex characteristics with static open-loop analysis and distensibility of the common carotid artery. Significant positive water and sodium balance was observed on the 1st day of 9% NaCl infusion; however, this disappeared by the 2nd day in Fat rats. Mean AP was significantly higher during 9% NaCl infusion in Fat rats compared with NFD rats. In the open-loop analysis of carotid sinus baroreflex, a rightward shift of the neural arc was observed in Fat rats compared with NFD rats. Furthermore, distensibility of the common carotid artery was significantly reduced in Fat rats. These results indicate that a reduced baroreceptor distensibility-induced rightward shift of the neural arc might contribute to impairment of sodium regulation in Fat rats.


Intestinal microvascular patterns during hemorrhagic shock.
While injuries due to a hypoxic state commonly appear later in both intestinal crypts and basal portion of the villi than in the apical portion, a nonhomogeneous distribution of blood flow in the intestinal mucosa may be supposed. The presence of two different microvascular plexuses inside the mucosa, corresponding to the cryptal plexus and the villous plexus, supports the above hypothesis. This work studies the intestinal microvasculature in shocked versus normal rats. Forty-five rats were divided into four groups to study the histological damage and the microvascular bed by ink injection, fluorescent microsphere infusion, and resin injection for scanning electron microscopy (SEM) of vascular corrosion cast (VCC) observations. An infusion pressure of 100 +/- 5 mm Hg was used in control animals, while 30 +/- 5 mm Hg infusion pressure was adopted for controls as well as for shocked animals to simulate physiological or shock conditions. Hemorrhagic shock was induced by removing blood and maintaining a mean arterial pressure of 30 +/- 5 mm Hg for 45-120 mins. A close connection among the patterns of microvasculature obtained with VCC and ink injection technique can be appreciated. In normal rats the whole microvasculature was visualized, but in both normal and shocked animals injected at low pressure different patterns could be found, generally showing a highly incomplete visualization of the vascular network. A significant decrease of visualization of both the entire microvasculature and the villous plexus is present in shocked animals when compared to unshocked controls, while no difference in the cryptal plexus visualization was observed. These observations suggest that the cryptal plexus is perfused preferentially during hemorrhagic shock, as a consequence of its peculiar microvascular organization. This may explain the relative resistance of the crypts, compared to villi, to hypoxic injuries in order to sustain endocrine function and the regenerative capability of the mucosa after prolonged hypoperfusion conditions that can lead to villous damage and temporary loss of the intestinal barrier function.


Screening Mexicans for psychosocial and behavioral problems during pediatric consultation.
Psychosocial and behavioral problems should be detected early during the pediatric consultation to prevent more severe psychosocial impairment as children move into adolescence. The pediatric visit offers an excellent opportunity to assess possible problems using screening tools. The aim of this study is to assess whether an adaptation of a screening tool (Pediatric Symptom Checklist) using visual aids is valid and suitable for the early detection of psychosocial problems among a sample of Mexican children and adolescents. We included 411 of 468 (87.8%) Mexican mothers or female caretakers of children and adolescents aged 4-16 undergoing routine health assessments in two Preventive Child Health Clinical Services in El Paso, Texas, USA. Mothers or female caretakers completed the Pictorial Pediatric Symptom Checklist and a psychological comprehensive test known as the Child Behavior Checklist (CBCL). Sensitivity and specificity was established using the CBCL as criteria for the validity of the PPSC. The PPSC screening tool performed well as demonstrated by its detection rates of psychosocial and behavioral problems among the sample of Mexican children. Sensitivity and specificity at the standard cut-off scores was 69.6% and 95.2% for children 4-5 years old and 61.8% and 91.8% for children 6-16 years old respectively. The results were slightly lower than those found using the PSC among other ethnic groups in the United States, with a sensitivity and specificity of 71.7% and 93.0%, respectively. The PPSC is a simple, effective tool that can detect on average more than 65% of the children and adolescents with possible psychosocial problems during pediatric consultations. This free screening tool detected psychosocial problems in pediatric populations of Mexican origin living on the border and may be also effective for Mexican children living in Mexico.


Metastasis-associated protein 1 promotes tumor invasion by downregulation of E-cadherin.
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. Upregulation of metastasis-associated protein 1 (MTA1) has been reported to contribute to the development of esophageal squamous cell carcinoma. Therefore, the objective of our study was to identify the molecular mechanisms of MTA1 underlying the invasion and metastasis of ESCC. We overexpressed MTA1 in ESCC cells to examine the role of MTA1 in the regulation of the cell invasion. In addition, using luciferase reporter assay and electrophoretic mobility shift assays, we evaluated the binding of MTA1 to the promoter of E-cadherin. We found that MTA1 overexpression promotes invasiveness of the human esophageal carcinoma cell line EC-9706. This effect was accompanied by downregulation of the epithelial cell marker E-cadherin and upregulation of vimentin and MMP-9 luciferase reporter assays showed that MTA1 inhibited the promoter activity of E-cadherin and that this was dependent on Snail, Slug and HDAC1. We also found that Snail and Slug bound the E-boxes in the promoter of E-cadherin and recruited MTA1 and HDAC1 to suppress E-cadherin expression, as confirmed by electrophoretic mobility shift and chromatin immunoprecipitation assays. MTA1 promotes tumor invasion by downregulation of E-cadherin. These results demonstrate a novel role for MTA1 in the regulation of esophageal squamous cell carcinoma invasion and provide insight into the mechanisms involved in this process.


Characterisation and functionalisation of chitosan nanoparticles as carriers for double-stranded RNA (dsRNA) molecules towards sustainable crop protection.
The need to minimise the impact of phytosanitary treatments for disease control boosted researchers to implement techniques with less environmental impact. The development of technologies using molecular mechanisms based on the modulation of metabolism by short dsRNA sequences appears promising. The intrinsic fragility of polynucleotides and the high cost of these techniques can be circumvented by nanocarriers that protect the bioactive molecule enabling high efficiency delivery to the leaf surface and extending its half-life. In this work, a specific protocol was developed aiming to assess the best methodological conditions for the synthesis of low-size chitosan nanoparticles (NPs) to be loaded with nucleotides. In particular, NPs have been functionalised with partially purified Green Fluorescent Protein dsRNAs (GFP dsRNA) and their size, surface charge and nucleotide retention capacity were analysed. Final NPs were also stained with FITC and sprayed on Nicotiana benthamiana leaves to assess, by confocal microscopy, both a distribution protocol and the fate of NPs up to 6 days after application. Finally, to confirm the ability of NPs to increase the efficacy of dsRNA interference, specific tests were performed: by means of GFP dsRNA-functionalised NPs, the nucleotide permanence during time was assessed both in vitro on detached wild-type N. benthamiana leaves and in planta; lastly, the inhibition of Botrytis cinerea on single leaves was also evaluated, using a specific fungal sequence (Bc dsRNA) as the NPs' functionalising agent. The encouraging results obtained are promising in the perspective of long-lasting application of innovative treatments based on gene silencing.


The impact of psychological distress tolerance in the treatment of depression.
Distress tolerance refers to the perceived ability to experience and withstand negative emotional states. Minimal research has investigated distress tolerance in the context of mood disorders despite poor emotional coping featuring in theoretical models of depression. The aims of the current investigation were to identify the relationship between psychological distress tolerance and depression, and to evaluate the impact of distress tolerance on treatment adherence and outcome following an internet-based cognitive behavioural therapy (iCBT) program for depression (the Sadness Program). Study 1 included 75 patients prescribed the Sadness Program by their primary care practitioner. Study 2 included 34 patients diagnosed with a major depressive episode participating in a randomized trial. Results of both studies indicated a significant inverse relationship between distress tolerance (DTS) and both depression severity (PHQ9) and psychological distress (K10). Results of intent-to-treat (ITT) marginal model analyses demonstrated that the Sadness Program was effective in reducing depression symptoms and psychological distress (Cohen's ds > 1), and in increasing distress tolerance (Cohen's ds > .28). However, patients who entered treatment with lower distress tolerance scores evidenced higher baseline and post-treatment scores on the outcome measures following iCBT. Collectively the findings suggest that distress tolerance is an important variable to consider in the context of treatments for depression. Clinical implications, future directions, and limitations are discussed.


Early neurosurgical intervention of spinal cord contusion: an analysis of 30 cases.
The incidence of spinal injury with spinal cord contusion is high in developed countries and is now growing in China. Furthermore, spinal cord injury happens mostly in young people who have a long life expectance. A large number of patients thus are wheelchair bound for the rest of their lives. Therefore, spinal cord injury has aroused great concern worldwide. Despite great efforts, recovery from spinal cord injury remains unsatisfactory. Based on the pathology of spinal cord contusion, an idea of early neurosurgical intervention has been formulated in this study. A total of 30 patients with "complete" spinal cord injury or classified as American Spinal Injury Association (ASIA)-A were studied. Orthopedic treatment of the injured vertebra (e), internal fixation of the vertebral column, and bilateral laminectomy for epidural decompression were followed directly by neurosurgical management, including separation of the arachnoid adhesion to restore cerebrospinal fluid flow and debridement of the spinal cord necrotic tissue with concomitant intramedullary decompression. Rehabilitation started 17 days after the operation. The final outcome was evaluated after 3 months of rehabilitation. Pearson chi-square analysis was used for statistical analysis. All the patients recovered some ability to walk. The least recovered patients were able to walk with a wheeled weight support and help in stabilizing the weight bearing knee joint (12 cases, 40%). Thirteen patients (43%) were able to walk with a pair of crutches, a stick or without any support. The timing of the operation after injury was important. An optimal operation time window was identified at 4 - 14 days after injury. Early neurosurgical intervention of spinal cord contusion followed by rehabilitation can significantly improve the locomotion of the patients. It is a new idea of a therapeutic approach for spinal cord contusion and has been proven to be very successful.


[Clinicopathologic features of glomus tumor of the kidney].
Objective: To investigate the clinicopathologic and differential diagnostic features of glomus tumor of the kidney. Methods: Four cases of glomus tumor of the kidney were collected from the archives of Peking University Third Hospital, the Second Hospital of Tianjin Medical University, Ningbo Yinzhou Second Hospital and Zhejiang Provincial People's Hospital between January 2012 to June 2017; the clinical and radiologic features, histomorphology, immunohistochemistry, ultrastucture and prognosis were analyzed and the relevant literature was reviewed. Results: Patients consisted of 2 men and 2 women with ages ranging from 37 years to 66 years (mean 55 years). Three patients had history of hypertensive disease (grade Ⅱ, 3 to 10 years). The tumors measured in maximum diameter from 3.0 cm to 4.0 cm (mean 3.6 cm) and showed gray-white to yellow and tan on cut surface. Macroscopical examinations showed all tumors were circumscribed but non-encapsulated. Histologically, 1 tumor presented as glomus tumor with extensive myxoid change, 1 as cellular and solid pattern glomus tumor, 1 as glomangioma with focal myopericytoma-like pattern and 1 as symplastic glomus tumor with areas resembling myopericytoma. The tumor cells in two cases showed scant cytoplasm and uniform, bland-appearing nuclei without mitoses. In one case, the tumor cells were epithelioid with abundant eosinophilic cytoplasm and relatively well-defined cell borders. There was an increased mitosis of 4/50 HPF; however, no evidence of atypical mitosis or nuclear atypia was noted. In the symplastic glomus tumor the tumor cells showed frequently nuclear pleomorphism without mitoses. By immunohistochemistry, all tumors showed strong and diffuse reactivities to at least 3 of the 4 muscle-associated markers (SMA, h-Caldesmon, MSA and Calponin), 3 tumors strongly and diffusely expressed collagen Ⅳ, 2 expressed CD34 and 1 focally expressed desmin; whereas markers including epithelial, neuroendocrine, nephrogenic, melanoma-associated, STAT6, S-100 protein, CD117 and β-catenin all were negative in all the 4 tumors. Ultrastuctural analysis was done in 2 cases and showed prominent cytoplasmic actin bundles and pericellular basement membrane, and lacking of rhomboid renin crystals in both tumors. The hypertension persisted after surgical resection for all the 3 patients with this medical history. Follow-up information (range: 6-64 months, mean: 44 months)showed that no evidence of local recurrence or distant metastasis was identified in all 4 patients. Conclusions: Glomus tumor rarely occurs in the kidney and usually has a good prognosis. Careful attention to its morphology with the judicious use of immunohistochemistry and ultrastuctural analysis can be helpful for its diagnosis and differential diagnosis.


Intracellular topography of rhodopsin regeneration in vertebrate rods.
The vertebrate visual pigment of rods, rhodopsin, bleaches in light and regenerates in darkness. When the bleaching and regeneration are carried out in vivo, it is found that the regeneration takes place at nonuniform rates along the rod outer segment (ROS): toads and frogs regenerate rhodopsin faster in the proximal ends of the ROS than in the distal ends. Rats do the reverse. These patterns of regeneration persist whether the bleaching is done with flashes or with steady light. They are also independent of the extent to which the retinal pigment epithelium contains melanin. Furthermore, the dichotomy of patterns (proximal faster vs. distal faster) does not seem to depend upon the presence of an excess of stored retinoid in the eye. Instead, it is suggested that the villous processes of the epithelial cells may play an important role in the regeneration patterns. These processes in amphibia extend nearly to the rod inner segment but in the rat they surround only the apical end of the outer segment. If they "funnel" the retinoids back to the ROS, their location and morphology could explain the two different kinds of patterns seen.


Vaccination practices for Leptospira spp. on New Zealand dairy farms.
To describe leptospiral vaccination practices in dairy herds in New Zealand and evaluate conformity with best practice guidelines issued by the New Zealand Veterinary Association using data from a questionnaire administered by participating veterinary practices. A cross-sectional study of 200 randomly selected dairy farms stratified by herd size and region throughout New Zealand was conducted from January to April 2016 to investigate leptospiral vaccination practices in dairy herds in New Zealand. Using a pre-tested questionnaire administered during a face-to-face interview, vaccination practice details such as vaccine types, time, and age of vaccination and whether vaccines were administered by veterinary or farm staff, were collected. Leptospiral vaccination programmes had been implemented on 199/200 (99.5 (95% CI = 97.2-99.9)%) farms, and on 178 (89.4%) of those, programmes had been running for ≥5 years. Most farmers used bivalent vaccines containing antigens for leptospiral serovars Pomona and Hardjo (144/179 (80.4%) in calves, 112/167 (60.7%) in heifers, and 112/163 (68.7%) in cows), rather than trivalent vaccines which also include antigens for L. interrogans serovar Copenhageni. In total, 123/200 (61.5%) of farmers purchased only vaccinated animals but 51/199 (25.6%) were unsure of the vaccination status of purchased cattle. Sixty-one percent (105/172) of farmers had other livestock on their farms and of them, 78/186 (42%) vaccinated some or all for Leptospira spp. Leptospiral vaccines were administered always or sometimes with other animal remedies on 30/190 (15.8%) and 91/190 (47.9%) of farms, respectively. Most farmers had not made changes to their vaccination programme in the previous 5 years. Timing of first vaccination of calves ranged from 2 weeks to 10 months of age, with 112/189 (59.3%) vaccinating by 4 months of age. Approximately half of the farms followed the best practice guideline for the timing of vaccinations for calves (high-risk farms; 67/162; 41.4%) heifers (72/165, 43.6%), and cows (171/184; 92.9%). The results of this survey suggest that there is almost universal adoption of leptospiral vaccination for dairy cattle in New Zealand. However, there remain areas for improvement regarding the proportion of farmers following best practice guidelines and refinement of vaccination programmes, particularly with respect to timing of vaccination in calves.


The natural course of traumatic triangular fibrocartilage complex tears in distal radial fractures: a 13-15 year follow-up of arthroscopically diagnosed but untreated injuries.
To evaluate the long-term results of a prospective, longitudinal case series of untreated, traumatic triangular fibrocartilage complex (TFCC) tears found in displaced distal radial fractures. Between 1995 and 1997, 51 patients (24 men, 27 women; age, 20-57 y) with a displaced distal radius fracture had wrist arthroscopy to identify associated injuries. Forty-three patients had complete or partial tears of the TFCC, which were not treated. All patients were contacted in 2010, 13-15 years after the injury. One patient had had a TFCC reattachment due to painful distal radioulnar joint instability and was excluded. Thirty-eight patients returned for a radiographic and clinical follow-up that recorded strength, distal radioulnar joint laxity, range of motion, pain scale score, and subjective and objective outcome scores. After 13-15 years, 17/38 patients were lax in the distal radioulnar joint. The mean grip strength was worse in the patients with a lax distal radioulnar joint (83%, SD 15 of the contralateral side vs 103%, SD 33). The median Gartland and Werley score was 5 (good; range, 0-15) in the lax group compared to 1 (excellent; range, 0-9) in the non-lax group, and the median Disabilities of the Arm, Shoulder, and Hand scores were 14 (range, 0-59) and 5 (range, 0-70) respectively. In this 13-15 year, prospective, longitudinal outcome study of the natural course of TFCC tears associated with distal radius fracture, only 1 patient had been operated on for painful instability since the injury. The subjective and objective results did not provide evidence that a TFCC injury would influence the long-term outcome. However, trends were found and, by speculation, the low number of patients in the series and the risk for a type II error could be the cause of absent statistically significance. Larger, preferably prospective, randomized studies are needed to find out whether a more aggressive treatment is beneficial. Diagnostic I.


Efficient photoacoustic imaging using indocyanine green (ICG) loaded functionalized mesoporous silica nanoparticles.
Photoacoustic (PA) imaging is gaining momentum due to its greater depth of field, low background, and 3D imaging capabilities. However, traditional PA imaging agents (e.g. dyes, quantum dots, etc.) are usually unstable in plasma and bind to serum proteins, and thus cleared rapidly. Because of this, the nanoparticle encapsulation of PA imaging agents is becoming increasingly popular. Therefore, the rational design of carrier nanoparticles for this purpose is necessary for strong imaging signal intensity, high biosafety, and precise targeting. Herein, we systematically evaluate the influence of the chemical and physical surface functionalization of mesoporous silica nanoparticles (MSNs) on the photo-stability, loading, release, and photoacoustic (PA) signal strength of the FDA approved small molecule contrast agent, indocyanine green (ICG). Chemical functionalization involved the modification of MSNs with silanes having amine (NH2) or phosphonate (PO3) terminal groups, whereas physical modifications were performed by capping the ICG loaded MSNs with lipid bilayer (LB) or layer-by-layer (LBL) polyelectrolyte coatings. The NH2-MSNs display the highest ICG mass loading capacity (16.5 wt%) with a limited release of ICG (5%) in PBS over 48 h, while PO3-MSNs only loaded ICG around 3.5 wt%. The physically modified MSNs (i.e. LBMSNs and LBLMSNs) were vacuum loaded resulting in approximately 9 wt% loading and less than 10% ICG release in 48 h. Pure ICG was highly photo-unstable and showed 20% reduction in photoluminescence (PL) within 3 h of exposure to 800 nm, while the ICG loaded onto functionalized MSNs did not photo-degrade. Among the tested formulations, NH2-MSNs and LBLMSNs presented 4-fold in vitro PA signal intensity enhancement at a 200 μg mL-1 equivalent ICG dose. Similar to the in vitro PA imaging, NH2-MSNs and LBLMSNs performed the best when subcutaneously injected into mouse cadavers with 1.29- and 1.43-fold PA signal enhancement in comparison to the pure ICG, respectively.


CAMSAP3 accumulates in the pericentrosomal area and accompanies microtubule release from the centrosome via katanin.
The epithelium has an apico-basal axis polarity that plays an important role in absorption, excretion and other physiological functions. In epithelial cells, a substantial number of non-centrosomal microtubules (MTs) are scattered in the cytoplasm with an apico-basal polarity and reorientate as epithelial cells perform different functions. Several previous studies have found that non-centrosomal MTs are nucleated at the centrosome, and then released and translocated elsewhere. However, the detailed process and molecular mechanism remain largely unknown. In this study, we found that Nezha, also called calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), a non-centrosomal MT minus-end protein, accumulates in the pericentrosomal area and accompanies the release of MTs from the centrosome; whereas depletion of CAMSAP3 prevented MT release and instead caused focusing of MTs at centrosomes. Further studies demonstrated that CAMSAP3 precisely coordinates with dynein and katanin to regulate the MT detachment process. In conclusion, our results indicate that CAMSAP3 is a key molecule for generation of non-centrosomal MTs.


Characterization and isolation of novel microsatellites from the Drosophila dunni subgroup.
We have isolated and characterized 77 novel microsatellites from two species, Drosophila dunni and Drosophila nigrodunni, which are closely related Caribbean-island endemics from the Drosophila cardini species group. These species are very distantly related to all other Drosophila from which microsatellites have previously been characterized. We find that the average length of microsatellites isolated in these species is quite small, with an overall mean length of 9.8 repeat units for dinucleotide microsatellites in the two study species. The nucleotide composition of dinucleotides differs between the two species: D. nigrodunni has a predominance of (AC/GT)n repeats, whereas D. dunni has equal numbers of (AC/GT)n and (AG/CT)n repeats. Tri- and tetranucleotide repeats are not abundant in either species. We assayed the variability of eight microsatellites in a closely related third species, Drosophila arawakana, using wild-caught individuals from the island of Guadeloupe. We found the microsatellites to be extremely variable in this population, with observed heterozygosities ranging from 0.541 to 0.889. DNA amplification trials suggest that these eight microsatellites are widely conserved across the D. cardini group, with five of the eight producing amplification products in every species tested. However, the loci are very poorly conserved over greater phylogenetic distances. DNA amplification of the microsatellite loci was unreliable in members of the closely related Drosophila quinaria, Drosophila calloptera, Drosophila guarani and Drosophila tripunctata species groups. Furthermore, these microsatellites could not be detected in the genome of Drosophila melanogaster, despite the conservation of microsatellite flanking regions at some loci. These data indicate that Drosophila microsatellite loci are quite short lived over evolutionary timescales relative to many other taxa.


The Impact of Initiation of an Intensivist-Led Patient Management Protocol on Outcomes After Cardiac Surgery.
Prolonged intensive care unit stay after cardiac surgery is associated with high mortality. The aim of this study was to evaluate the impact of the introduction of a quality improvement program under the supervision of an intensivist on the long-term mortality of high-risk patients with prolonged intensive care unit (ICU) stay after cardiac surgery. Retrospective study of prospectively collected data. Cardiac surgery ICU. A total of 7,549 patients after cardiac surgery. Patients were divided into two periods: 2004 to 2007, before introducing the quality improvement program (3,315 patients), and 2009 to 2014, after introduction of the program (4,234 patients). In the period from 2004 to 2007, patients were divided into group I (ICU stay ≥ seven days), which included 242 patients, and group III (ICU stay < seven days), which included 3,073 patients. Also, in the period from 2009 to 2014 patients, were divided into group II (ICU stay ≥seven days), which included 326 patients, and group IV (ICU stay < seven days), which included 3,908 patients. Patient outcomes were compared. Follow-up was five years for each group. The European System for Cardiac Operative Risk Evaluation did not differ significantly among the groups. When comparing between group I and group II, 30-day mortality decreased significantly from 24.8% to 16.6%, six-month mortality from 27.3% to 19.3%, one-year mortality from 42.1% to 32.2%, 3-year mortality from 54.5% to 43.3%, and 5-year mortality from 61.2% to 51.8%. In comparing between group III and group IV, the authors did not observe a statistically significant decrease of mortality. Intensivist-led patient management protocol is associated with decreased long-term mortality in high-risk patients with a prolonged ICU stay.


In Vitro Utilization Characteristics of Maltobionic Acid and Its Effects on Bowel Movements in Healthy Subjects.
We examined the in vitro digestibility of maltobionic acid, obtained from enzymatic oxidation of maltose, its utilization by intestinal bacteria, and its biological effects on the bowel movements in healthy subjects. We found that maltobionic acid is not digested in vitro by saliva, gastric juice, or pancreatic juice. Moreover, it is digested only to a small extent by small intestinal enzymes. Among the 24 strains of intestinal bacteria, maltobionic acid was selectively utilized by Bifidobacterium dentium and Bi. adolescentis. We also evaluated the influence of long-term ingestion of maltobionic acid calcium salt on bowel movements in healthy Japanese women by a randomized, double-blind, placebo-controlled, crossover trial. Thirty-four subjects completed the study, and no adverse events related to the test food were observed. Ten subjects were excluded prior to the efficacy analysis because of conflict with the control criteria; the remaining 24 subjects were analyzed. Intake of test food containing 4 g maltobionic acid for 4 weeks caused a significant increase in the stool frequency, significant improvement in stool form scale and CAS-MT total scores as compared with the placebo group. These results suggest that maltobionic acid is an indigestible carbohydrate and is a promising therapeutic agent for improving the intestinal environment.


Large retropharyngeal abscess: a case of mistaken identity.
We report an unusual case of nasopharyngeal carcinoma (NPC), presenting initially as a retropharyngeal collection. We discuss the investigation, diagnosis and management of NPC and furthermore review the literature of NPC, emphasising the varied presentation. A 44-year-old Caucasian male ex-smoker presented with a 10-day history of a painless left-sided neck lump; progressive dysphagia and unintentional weight loss. Examination demonstrated a large left posterior pharyngeal swelling with soft palatal effacement, confirmed on nasoendoscopy. A CT scan revealed a fluid collection in the retropharyngeal space, which partially occluded the nasopharynx, and numerous satellite lesions were identified along with cervical lymphadenopathy. The suspected abscess was drained in theatre and nasopharyngeal biopsies were taken. These revealed Epstein-Barr virus-positive NPC. Staging investigations revealed a T4N2M0l carcinoma. Treatment consisted of radical chemoradiation therapy with curative intent. NPC is known for its varied and late presentation, and is an important condition to be aware of when considering a differential diagnosis of pharyngeal masses.


Rapid extraction of auditory feature contingencies.
Contingent relations between sensory events render the environment predictable and thus facilitate adaptive behavior. The human capacity to detect such relations has been comprehensively demonstrated in paradigms in which contingency rules were task-relevant or in which they applied to motor behavior. The extent to which contingencies can also be extracted from events that are unrelated to the current goals of the organism has remained largely unclear. The present study addressed the emergence of contingency-related effects for behaviorally irrelevant auditory stimuli and the cortical areas involved in the processing of such contingency rules. Contingent relations between different features of temporally separate events were embedded in a new dynamic protocol. Participants were presented with the auditory stimulus sequences while their attention was captured by a video. The mismatch negativity (MMN) component of the event-related brain potential (ERP) was employed as an electrophysiological correlate of contingency detection. MMN generators were localized by means of scalp current density (SCD) and primary current density (PCD) analyses with variable resolution electromagnetic tomography (VARETA). Results show that task-irrelevant contingencies can be extracted from about fifteen to twenty successive events conforming to the contingent relation. Topographic and tomographic analyses reveal the involvement of the auditory cortex in the processing of contingency violations. The present data provide evidence for the rapid encoding of complex extrapolative relations in sensory areas. This capacity is of fundamental importance for the organism in its attempt to model the sensory environment outside the focus of attention.


White matter integrity in schizophrenia and bipolar disorder: Tract- and voxel-based analyses of diffusion data from the Connectom scanner.
Diffusion imaging abnormalities have been associated with schizophrenia (SZ) and bipolar disorder (BD), indicating impaired structural connectivity. Newer methods permit the automated reconstruction of major white matter tracts from diffusion-weighted MR images in each individual's native space. Using high-definition diffusion data from SZ and BP subjects, we investigated brain white matter integrity using both an automated tract-based and voxel-based methods. Using a protocol matched to the NIH (Young-Adult) Human Connectome Project (and collected on the same customized 'Connectom' scanner), diffusion scans were acquired from 87 total participants (aged 18-30), grouped as SZ (n = 24), BD (n = 33) and healthy controls (n = 30). Fractional anisotropy (FA) of eighteen white matter tracks were analyzed using the TRACULA software. Voxel-wise statistical analyses of diffusion data was carried out using the tract-based spatial statistics (TBSS) software. TRACULA group effects and clinical correlations were investigated using analyses of variance and multiple regression. TRACULA analysis identified a trend towards lower tract FA in SZ patients, most significantly in the left anterior thalamic radiation (ATR; p = .04). TBSS results showed significantly lower FA voxels bilaterally within the cerebellum and unilaterally within the left ATR, posterior thalamic radiation, corticospinal tract, and superior longitudinal fasciculus in SZ patients compared to controls (FDR corrected p < .05). FA in BD patients did not significantly differ from controls using either TRACULA or TBSS. Multiple regression showed FA of the ATR as predicting chronic mania (p = .0005) and the cingulum-angular bundle as predicting recent mania (p = .02) in patients. TBSS showed chronic mania correlating with FA voxels within the left ATR and corpus callosum. White matter abnormality in SZ varies in severity across different white matter tract regions. Our results indicate that voxel-based analysis of diffusion data is more sensitive than tract-based analysis in identifying such abnormalities. Absence of white matter abnormality in BD may be related to medication effects and age.


Implantation of scleral-fixated posterior chamber intraocular lenses.
A surgical technique for implanting a posterior chamber intraocular lens (IOL) in eyes without capsular or zonular support is presented. A 10-0 polypropylene suture attached to a standard needle is tied to the apex of each haptic and passed transclerally through the ciliary sulcus to secure the haptics at the 3 o'clock and 9 o'clock meridians. This technique produced good visual results in six aphakic patients who were contact lens intolerant, two patients in whom capsular or zonular rupture at the time of cataract surgery precluded standard nonsuture fixation techniques, one patient who had intracapsular cataract extraction for a subluxated, cataractous lens, and one patient who had secondary IOL implantation in combination with penetrating keratoplasty for aphakic bullous keratopathy. Advantages over other techniques of posterior chamber lens implantation in the absence of capsular support include technical ease, avoidance of iris fixation, and more precise placement of scleral fixation sutures, thus minimizing IOL decentration.


Surface-enhanced Raman spectroscopy characterisation of functionalised multi-walled carbon nanotubes.
Multi-walled nanotube (MWNT) functionalisation was investigated by surface-enhanced Raman spectroscopy (SERS). The MWNTs were deposited as dilute dispersions on SERS-active substrates. We used nano-structured gold surfaces with various morphologies for our measurements. The surface enhancement effect was used to amplify the Raman signal from functional molecules bound to the nanotube walls. The recorded spectral features allowed for discrimination between the differently functionalised MWNTs. Although the present study is limited to a few examples, our measurements indicate the higher specificity obtained by the SERS approach and its possible use for a systematic study of functionalisation effects on MWNT structures.


DNA sequence of the viral and cellular src gene of chickens. 1. Complete nucleotide sequence of an EcoRI fragment of recovered avian sarcoma virus which codes for gp37 and pp60src.
Recovered avian sarcoma virus is a class of virus obtained from chicken tumors induced by mutants of Rous sarcoma virus which have a deletion in the src gene. We have determined the entire nucleotide sequence of a 3.1-kilobase EcoRI DNA fragment of molecularly cloned recovered avian sarcoma virus DNA. This DNA fragment contains part of the env gene and the entire src gene. Amino acid sequences of both gene products were deduced from the DNA sequences; the predicted amino acid sequences were verified by protein studies. An env protein (gp37) was found to be composed of 205 amino acids with three glycosylation sites. gp37 had a long stretch of hydrophobic residues near the carboxyl terminus. The src gene product, pp60src, was composed of 526 amino acids and contained the possible sites for tyrosine and serine phosphorylation. The amino acid sequences predicted in this study differ significantly from the amino acid sequence predicted previously for the Schmidt-Ruppin strain of Rous sarcoma virus.


A history of pediatric tracheal surgery.
Tracheal stenosis in children is primarily caused by congenital complete cartilage tracheal rings. These infants present with severe respiratory distress early in life. The purpose of this review is to examine the history of surgical intervention for infants and children with congenital tracheal stenosis. Most of the significant advances in the surgical treatment of patients with congenital tracheal stenosis have occurred over the past 50 years. The highlights of the historical events include the first pulmonary artery sling repair (1953), tracheal resection (1958), cartilage tracheoplasty (1981), pericardial tracheoplasty (1982), slide tracheoplasty (1989), homograft tracheoplasty (1994), and tracheal autograft (1996). The results of surgical intervention on patients with congenital tracheal stenosis have steadily improved, particularly during the past 20 years. Most successful centers are using cardiopulmonary bypass, simultaneous repair of associated pulmonary artery sling and cardiac anomalies, and the current procedure of choice-slide tracheoplasty. During the past 50 years, significant advances have been made in the care of infants with congenital tracheal stenosis. The outlook for these children is currently quite good, and successful outcomes are particularly evident at institutions with a careful multidisciplinary approach to these patients.


Barriers to sustainable MVA supply in Ghana: challenges for the low-volume, low-income providers.
Multiple studies have demonstrated that manual vacuum aspiration (MVA) is ideal for surgical uterine evacuation in low-resource settings such as Ghana, but developing a sustainable supply to MVA has been challenging. In 2007 a situational analysis was conducted in Ghana to identify barriers to sustainable MVA supply. Information about MVA availability was gathered in seven regions of Ghana and obtained through background literature, unpublished data and reports, and 70 informational interviews with stakeholders involved with MVA policy, manufactufing, procurement, distribution, supply, training, and provision. The findings revealed that despite consensus about the dire need for MVA in Ghana, developing sustainable access to MVA instruments has proven difficult. In the public and the private health sectors, procuring MVA equipment has been particularly challenging for low-income, low-volume service providers. Research findings yielded ten recommendations for improving sustainable access to MVA, including the implementation of a revolving purchase mechanismn for health provider associations, such as the Ghana Registered Midwives Association.


[Diagnostic possibilities of bone scintigraphy in osteoarticular tuberculosis].
Skeleton scintigraphy with 99mTc-technefor was conducted in 71 patients with bone and joint tuberculosis and in 3 patients with nonspecific spinal diseases. The method was found to be highly sensitive in the diagnosis of a specific process, its localization, dissemination and activity. A correlation was revealed between the quantitative characteristics of isotope accumulation and morphologic signs of tuberculosis activity. Simultaneous visualization of the kidneys made it possible to diagnose their pathology.


Shy Girl, a kiwifruit suppressor of feminization, restricts gynoecium development via regulation of cytokinin metabolism and signalling.
Kiwifruit (Actinidia chinensis) is a dioecious, long-living woody perennial vine. Reduced generation time and induction of hermaphroditism can accelerate crop improvement and facilitate alternative farming for better food security in the face of climate change. Previous studies identified that CENTRORADIALIS genes CEN and CEN4 act to repress flowering, whilst the male-specific Shy Girl (SyGl) gene with homology to type-C cytokinin response regulators could repress gynoecium development in model plants. Here we use CRISPR/Cas9 to mutagenize CEN, CEN4 and SyGl in the male kiwifruit A. chinensis 'Bruce'. Biallelic mutations of CEN and CEN4 generated rapid-flowering male plants, and simultaneous targeting of CEN4 and SyGl gave rise to rapid-flowering hermaphrodites with restored gynoecial function and viable pollen, providing functional evidence for the role of SyGl in suppression of feminization. Analysis of ovary tissues identified genes that contribute to carpel development and revealed that SyGl affected both cytokinin profiles and the expression of genes involved in cytokinin metabolism and signalling. The plant lines generated by CEN4/SyGl knockout could self-pollinate and produce fast-flowering offspring. These results establish that SyGI acts as the suppressor of feminization in kiwifruit and demonstrate the potential for accelerated breeding in an outcrossing horticultural woody perennial.


Assessment of beta-adrenergic blockade with propranolol in patients with cirrhosis.
Fourteen patients with cirrhosis and bleeding esophageal varices were treated with propranolol. The dose of propranolol was determined by decreasing the resting heart rate by 25% 12 hr after an oral dose of propranolol which was given twice a day. Significant decreases in the hepatic venous pressure gradient and cardiac output after 1 month of propranolol administration was observed. To assess beta-adrenergic blockade, the isoproterenol test and plasma propranolol levels were evaluated. Increasing doses of isoproterenol were injected to increase the resting heart rate 25 beats per minute (chronotropic dose 25 or CD25 ). Plasma propranolol concentrations were measured in blood samples drawn 4 hr after the last oral dose. The mean CD25 was 5 +/- 2 micrograms before and 146 +/- 84 micrograms after 1 month of propranolol administration. The plasma propranolol level after 1 month of drug administration was 0.69 +/- 0.47 microM per liter i.e. 2.33 +/- 1.59 micrograms per ml. A significant correlation was found between the CD25 measured after continuous propranolol administration and plasma propranolol level. In conclusion, the efficacy of beta-adrenergic blockade was estimated by the isoproterenol test which correlates with the plasma propranolol level in patients with cirrhosis. This study suggests that the isoproterenol test is useful in assessing beta-adrenergic blockade with propranolol in patients with cirrhosis.


Hyperexcitability in Spinal WDR Neurons following Experimental Disc Herniation Is Associated with Upregulation of Fractalkine and Its Receptor in Nucleus Pulposus and the Dorsal Root Ganglion.
Introduction. Lumbar radicular pain following intervertebral disc herniation may be associated with a local inflammatory response induced by nucleus pulposus (NP) cells. Methods. In anaesthetized Lewis rats, extracellular single unit recordings of wide dynamic range (WDR) neurons in the dorsal horn and qPCR were used to explore the effect of NP application onto the dorsal nerve roots (L3-L5). Results. A clear increase in C-fiber response was observed following NP conditioning. In the NP tissue, the expression of interleukin-1β (IL-1β), colony stimulating factor 1 (Csf1), fractalkine (CX3CL1), and the fractalkine receptor CX3CR1 was increased. Minocycline, an inhibitor of microglial activation, inhibited the increase in neuronal activity and attenuated the increase in IL-1β, Csf1, CX3L1, and CX3CR1 expression in NP tissue. In addition, the results demonstrated an increase in the expression of TNF, CX3CL1, and CX3CR1 in the dorsal root ganglions (DRGs). Conclusion. Hyperexcitability in the pain pathways and the local inflammation after disc herniation may involve upregulation of CX3CL1 signaling in both the NP and the DRG.