Synthesis and characterization of 5,10,15,20-tetra[3-(3-trifluoromethyl)phenoxy] porphyrin.
The newly synthesized 5,10,15,20-tetra[3-(3-trifluoromethyl)phenoxy]porphyrin, TTFMPP, has been characterized using mass spectroscopy, 1H-, 13C- and 19F-NMR, MALDI-TOF mass spectrometry, UV-Vis and fluorescence spectrophotometry, and cyclic voltammetry. The NMR confirmed the structure of the compound and the mass spectrum was in agreement with the proposed molecular formula. The UV-Vis absorption spectrum of TTFMPP shows characteristic spectral patterns similar to those of tetraphenyl porphryin, with a Soret band at 419 nm and four Q bands at 515, 550, 590, and 648 nm. Protonation of the porphyrin with TFA resulted in the expected red shift of the Soret band. Excitation at 419 nm gave an emission at 650 nm. The quantum yield of the porphyrin was determined to be 0.08. Cyclic voltammetry was used to determine the oxidation and reduction potentials of the new porphyrin. Two quasi-reversible one-electron reductions at -1.00 and -1.32 V and a quasi-reversible oxidation at 1.20 V versus the silver/silver chloride reference electrode with tetrabutylammonium tetrafluoroborate as the supporting electrolyte in methylene chloride were observed.


Active borna disease virus polymerase complex requires a distinct nucleoprotein-to-phosphoprotein ratio but no viral X protein.
Analysis of the composition and regulation of the Borna disease virus (BDV) polymerase complex has so far been limited by the lack of a functional assay. To establish such an assay on the basis of an artificial minigenome, we constructed expression vectors encoding either nucleoprotein (N), phosphoprotein (P), X protein, or polymerase (L) of BDV under the control of the chicken beta-actin promoter. A Flag-tagged version of L colocalized with virus-encoded N and P in characteristic nuclear dots of BDV-infected cells and increased viral N-protein levels in persistently infected Vero cells. Vector-driven expression of L, N, and P in BSR-T7 cells together with a negative-sense BDV minigenome carrying a chloramphenicol acetyltransferase (CAT) reporter gene resulted in efficient synthesis of CAT protein. Induction of CAT protein synthesis strongly depended on a 10- to 30-fold molar excess of the N-encoding plasmid over the P-encoding plasmid. Cotransfection of even small amounts of plasmid encoding the viral X protein reduced CAT synthesis to background levels. Thus, the N-to-P stoichiometry seems to play a central role in the regulation of the BDV polymerase complex. Our data further suggest a negative regulatory function for the X protein of BDV.


Comparing the injectate spread and nerve involvement between different injectate volumes for ultrasound-guided greater occipital nerve block at the C2 level: a cadaveric evaluation.
The spread patterns between different injectate volumes have not yet been investigated in ultrasound-guided greater occipital nerve (GON) block at the C2 level. This cadaveric study was undertaken to compare the spread pattern and nerve involvements of different volumes of dye using this technique. After randomization, ultrasound-guided GON blocks with 1 or 5 mL dye solution were performed at the C2 level on the right or left side of five fresh cadavers. The suboccipital regions were dissected, and nerve involvement was investigated. Ten injections were successfully completed. In all cases of 5 mL dye, we observed the deeply stained posterior neck muscles, including the suboccipital triangle space. The suboccipital and third occipital nerves, in addition to GONs, were consistently stained when 5-mL dye was used in all injections (100%). Although all GONs were successfully stained in the 1-mL dye cases, three of five injections (60%) concomitantly stained the third occipital nerves. The clinical efficacy of this technique using the 5-mL injectate seems unlikely to arise from the blockade of GON alone. Instead, its efficacy likely arises from the blockade of most nerves originating from the dorsal ramus of the upper cervical spinal nerve at the suboccipital area. Even using 1 mL of injectate may not guarantee blockade of the GON alone.


Using flow diagrams to improve tobacco cessation programs.
Purpose The purpose of this paper is to understand how the Wyoming Quit Tobacco Program (WQTP) is used by its subscribers and to better understand how WQTP might be connected to WQTP outcomes. Design/methodology/approach Provider intake and program use data corresponding to the May 2010 to March 2012 enrollment period ( n=6,168) were used. All program flows were constructed using frequencies and crosstabs, based on an initial theoretical model prepared by the program provider. Data were adjusted based on analysis that explored all possible uses beyond those specified by the provider's theoretical model. Findings Although the authors could replicate the structure - the theoretical model constructed by the provider - the authors were not able to replicate all relationships between program components. The authors also found that most individuals signed up and used web-based services. Only a few individuals finished their treatment regimens in the way they were designed to be used by the program. Originality/value This is the first case study to use a program flow method to investigate an entire comprehensive tobacco cessation program structure and delivery.


Condylar asymmetry in children with juvenile idiopathic arthritis assessed by cone-beam computed tomography.
The purpose of this study was to determine the degree of condylar asymmetry in children with juvenile idiopathic arthritis (JIA) using cone-beam computed tomography (CBCT) and analysis software. For 20 patients (14 girls and six boys; mean age 11.21 +/- 3.54 years), resultant cross-sectional images of the left and right temporomandibular joints (TMJs) were semi-automatically segmented, and exact registration of the right, with respect to the flipped left grey-level condyle, was obtained. Visual inspection of the volume images in 360 degree rotation showed a wide variety of condylar destruction patterns, ranging from small erosions within the cortex to almost complete deformation of the condylar head. Because segmentation was restricted to the delineation of the cortical region, possible changes in the deeper zones were not reproduced. Descriptive statistics [median and interquartile range (IQR)] and diagrams (frequency distribution) were used to assess the results. Initial analysis of condylar volume (including both flipped left and right) showed a median value for volume of 0.844 cm(3) (IQR 0.323), while the median value for volume difference between both condyles was 0.051 cm(3) (IQR 0.098). Analysis of the degree of asymmetry showed a median value of 26.18 per cent (IQR 14.46). Using the CBCT-based method, it was shown that condylar asymmetry was a common feature in children with JIA. The degree of asymmetry was variable, but significant in the majority of the subjects.


Myotubularin functions through actomyosin to interact with the Hippo pathway.
The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size by integrating diverse regulatory inputs, including actomyosin-mediated cytoskeletal tension. Despite established connections between the actomyosin cytoskeleton and the Hippo pathway, the upstream regulation of actomyosin in the Hippo pathway is less defined. Here, we identify the phosphoinositide-3-phosphatase Myotubularin (Mtm) as a novel upstream regulator of actomyosin that functions synergistically with the Hippo pathway during growth control. Mechanistically, Mtm regulates membrane phospholipid PI(3)P dynamics, which, in turn, modulates actomyosin activity through Rab11-mediated vesicular trafficking. We reveal PI(3)P dynamics as a novel mode of upstream regulation of actomyosin and establish Rab11-mediated vesicular trafficking as a functional link between membrane lipid dynamics and actomyosin activation in the context of growth control. Our study also shows that MTMR2, the human counterpart of Drosophila Mtm, has conserved functions in regulating actomyosin activity and tissue growth, providing new insights into the molecular basis of MTMR2-related peripheral nerve myelination and human disorders.


Population pharmacokinetics and pharmacodynamic evaluation of intravenous and enteral moxifloxacin in surgical intensive care unit patients.
To describe the plasma concentration-time profile of moxifloxacin after intravenous and enteral administration in intensive care unit (ICU) patients and to provide a pharmacodynamic (PD) evaluation with regard to pneumonia. Twenty-five adult patients from a cardiothoracic/mixed surgical ICU were enrolled. Moxifloxacin was given as a standard dose (400 mg once daily). Therapy was successfully switched to enteral administration on day 5 in 16 patients. A rich data sampling schedule was performed after intravenous (day 4) and enteral (day 8) administration. Moxifloxacin concentrations were analysed by HPLC. A population pharmacokinetic (PK) model was developed using NONMEM VII. Simulated concentration-time profiles were evaluated for their probability of attaining PK/PD target values relevant for community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). A linear-elimination two-compartment model described the data adequately. Parameter estimates (coefficient of variation of inter-individual variability) were: absorption rate constant, 1.09/h (135%); enteral bioavailability, 76% (20.0%); central volume of distribution, 55.6 L; peripheral volume of distribution, 59.6 L (15.3%); inter-compartmental clearance, 47.7 L/h; and clearance, 11.3 L/h (23.7%). Both intravenously and enterally administered standard-dose moxifloxacin reliably attained the PK/PD target values for pathogens with MICs ≤ 0.25 mg/L for CAP and ≤ 0.125 mg/L for HAP. Drug exposure to moxifloxacin in ICU patients was more variable than in healthy volunteers. The standard dosing provides sufficient drug exposure for treatment of CAP but for HAP it does so only when a highly susceptible pathogen is present. Intravenous/enteral sequential therapy may be considered for cautiously selected cases in ICU patients.


Journeying to professionalism: the case of Irish nursing and midwifery research.
This paper gives a 'discursive' account of the contemporary development of nursing and midwifery research in the Republic of Ireland in the context of advancing professionalism. Initially, the paper views the landscape by placing research in the current framework of Irish nursing and midwifery. It then examines the map of our present location by documenting a baseline. It ascertains the signposts that are in place by exploring the strategic direction for development. Finally, it uses the compass to orienteer the route through the various obstacles by examining the challenges of the role of the joint appointee leading the implementation of the national Research Strategy for Nursing and Midwifery in Ireland.


Subarachnoid hemorrhage following chronic dural venous sinus thrombosis.
Subarachnoid hemorrhage (SAH) in older individuals is most often due to aneurysmal rupture. Other vascular lesions are known to rarely cause SAH. In this article, we report a case of chronic dural sinus thrombosis with recurrent SAH, most probably due to raised venous pressure in draining venous tributaries. No aneurysm was detected on magnetic resonance angiography or on digital subtraction angiography. The patient improved with conservative management. The case report emphasizes inclusion of magnetic resonance venography in the diagnostic workup of SAH, particularly in those cases in which aneurysm is not detected.


Three novel cantharidin-related compounds from the Chinese blister beetle, Mylabris phalerata Pall.
Three novel cantharidin analogues were isolated from the Chinese blister beetle, Mylabris phalerata PALL. (Meloidae), which has been used in traditional Chinese medicine for the treatment of cancer. Their structures were determined on the basis of heteronuclear multiple-bond connectivity and nuclear Overhauser effect spectroscopy experiments, and chemical data confirmed them to be so-called cantharimides, in which the anhydride oxygen atoms are replaced by the basic amino acid L-lysine, L-ornithine, and L-arginine moieties.


Synthesis, Antifungal Activities, Molecular Docking and Molecular Dynamic Studies of Novel Quinoxaline-Triazole Compounds.
Uncontrolled use of antifungal drugs affects the development of resistance to existing drugs. Azole antifungals constitute a large part of antifungal therapy. Therefore, there is a need for new azole antifungals. Within the scope of this study, 17 new triazole derivative compounds were synthesized. Structure determinations were clarified by spectroscopic analysis methods (1H-NMR, 13C-NMR, HRMS). In addition, structure matching was completed using two-dimensional NMR techniques, HSQC, HMBC and NOESY. The antifungal effects of the compounds were evaluated on Candida strains by means of in vitro method. Compound 5d showed activity against Candida glabrata with a MIC90 = 2 μg/mL. Compound 5d showed activity against Candida krusei with a MIC90 = 2 μg/mL. This activity value, which is higher than fluconazole, is promising. In addition, the biofilm inhibition percentages of the compounds were calculated. Molecular docking and molecular dynamics simulations performed with compound 5d are in harmony with activity studies.


Management of painful reverse shoulder arthroplasty.
Even though reverse shoulder arthroplasty is a very successful procedure, painful complications occur. During the initial postoperative years, the most common reasons for pain are instability, postoperative fracture of the acromion or spine, and periprosthetic infection. Later, aseptic loosening, with humeral loosening being more frequent that glenoid loosening, can be a source of pain and reduction in function. A careful patient history, clinical examination, plain radiographs, computed tomography and blood tests give an explanation for the pain in most cases. The majority of these complications can be successfully treated, maintaining a functional reverse shoulder arthroplasty. However, if all examinations are normal, it is important to remember that nonshoulder conditions such as tumour of the lung or degenerative changes of the cervical spine can give shoulder pain.


Motion estimation in beating heart surgery.
Minimally invasive beating-heart surgery offers substantial benefits for the patient, compared to conventional open surgery. Nevertheless, the motion of the heart poses increased requirements to the surgeon. To support the surgeon, algorithms for an advanced robotic surgery system are proposed, which offer motion compensation of the beating heart. This implies the measurement of heart motion, which can be achieved by tracking natural landmarks. In most cases, the investigated affine tracking scheme can be reduced to an efficient block matching algorithm allowing for realtime tracking of multiple landmarks. Fourier analysis of the motion parameters shows two dominant peaks, which correspond to the heart and respiration rates of the patient. The robustness in case of disturbance or occlusion can be improved by specially developed prediction schemes. Local prediction is well suited for the detection of single tracking outliers. A global prediction scheme takes several landmarks into account simultaneously and is able to bridge longer disturbances. As the heart motion is strongly correlated with the patient's electrocardiogram and respiration pressure signal, this information is included in a novel robust multisensor prediction scheme. Prediction results are compared to those of an artificial neural network and of a linear prediction approach, which shows the superior performance of the proposed algorithms.


Effect of Genetic Modifications on Physical and Functional Titers of Adenoviral Cancer Gene Therapy Constructs.
After the discovery and characterization of the adenovirus in the 1950s, this prevalent cause of the common cold and other usually mild diseases has been modified and utilized in biomedicine in several ways. To date, adenoviruses are the most frequently used vectors and therapeutic (e.g., oncolytic) agents with a number of beneficial features. They infect both dividing and nondividing cells, enable high-level, transient protein expression, and are easy to amplify to high concentrations. As an important and versatile research tool, it is of essence to understand the limits and advantages that genetic modification of adenovirus vectors may entail. Therefore, a retrospective analysis was performed of adenoviral gene therapy constructs produced in the same laboratory with similar methods. The aim was to assess the impact of various modifications on the physical and functional titer of the virus. It was found that genome size (designed within "the 105% golden rule") did not significantly affect the physical titer of the adenovirus preparations, regardless of the type of transgene (e.g., immunostimulatory vs. other), number of engineered changes, and size of the mutated virus genome. One statistically significant exception was noted, however. Chimeric adenoviruses (5/3) had a slightly lower physical titer compared to Ad5-based viruses, although a trend for the opposite was true for functional titers. Thus, 5/3 chimeric viruses may in fact be appealing from a safety versus efficacy viewpoint. Armed viruses had lower functional and physical titers than unarmed viruses, while five genomic modifications started to decrease functional titer. Importantly, even highly modified armed viruses generally had good titers compatible with clinical testing. In summary, this paper shows the plasticity of adenovirus for various vector, oncolytic, and armed oncolytic uses. These results inform future generations of adenovirus-based drugs for human use. This information is directly transferable to academic laboratories and the biomedical industry involved in vector design and production optimization.


Sir2 deacetylates histone H3 lysine 56 to regulate telomeric heterochromatin structure in yeast.
At telomeric heterochromatin in yeast, the Sir protein complex spreads from Rap1 sites to silence adjacent genes. This cascade is believed to occur when Sir2, an NAD(+)-dependent enzyme, deacetylates histone H3 and H4 N termini, in particular histone H4 K16, enabling more Sir protein binding. Lysine 56 of histone H3 is located at the entry-exit points of the DNA superhelix surrounding the nucleosome, where it may control DNA compaction. We have found that K56 substitutions disrupt silencing severely without decreasing Sir protein binding at the telomere. Our in vitro and in vivo data indicate that Sir2 deacetylates K56 directly in telomeric heterochromatin to compact chromatin and prevent access to RNA polymerase and ectopic bacterial dam methylase. Since the spread of Sir proteins is necessary but not sufficient for silencing, we propose that silencing occurs when Sir2 deacetylates H3 K56 to close the nucleosomal entry-exit gates, enabling compaction of heterochromatin.


Cyanobacteria as efficient producers of mycosporine-like amino acids.
Mycosporine-like amino acids are the most common group of transparent ultraviolet radiation absorbing intracellular secondary metabolites. These molecules absorb light in the range of ultraviolet-A and -B with a maximum absorbance between 310 and 362 nm. Cyanobacteria might have faced the most deleterious ultraviolet radiation, which leads to an evolution of ultraviolet protecting mycosporine-like amino acids for efficient selection in the environment. In the last 30 years, scientists have investigated various cyanobacteria for novel mycosporine-like amino acids, applying different induction techniques. This review organizes all the cyanobacterial groups that produce various mycosporine-like amino acids. We found out that cyanobacteria belonging to orders Synechococcales, Chroococcales, Oscillatoriales, and Nostocales are frequently studied for the presence of mycosporine-like amino acids, while orders Gloeobacterales, Spirulinales, Pleurocapsales, and Chroococcidiopsidales are still need to be investigated. Nostoc and Anabaena strains are major studied genus for the mycosporine-like amino acids production. Hence, this review will give further insight to the readers about potential mycosporine-like amino acid producing cyanobacterial groups in future investigations.


Robust prediction of consensus secondary structures using averaged base pairing probability matrices.
Recent transcriptomic studies have revealed the existence of a considerable number of non-protein-coding RNA transcripts in higher eukaryotic cells. To investigate the functional roles of these transcripts, it is of great interest to find conserved secondary structures from multiple alignments on a genomic scale. Since multiple alignments are often created using alignment programs that neglect the special conservation patterns of RNA secondary structures for computational efficiency, alignment failures can cause potential risks of overlooking conserved stem structures. We investigated the dependence of the accuracy of secondary structure prediction on the quality of alignments. We compared three algorithms that maximize the expected accuracy of secondary structures as well as other frequently used algorithms. We found that one of our algorithms, called McCaskill-MEA, was more robust against alignment failures than others. The McCaskill-MEA method first computes the base pairing probability matrices for all the sequences in the alignment and then obtains the base pairing probability matrix of the alignment by averaging over these matrices. The consensus secondary structure is predicted from this matrix such that the expected accuracy of the prediction is maximized. We show that the McCaskill-MEA method performs better than other methods, particularly when the alignment quality is low and when the alignment consists of many sequences. Our model has a parameter that controls the sensitivity and specificity of predictions. We discussed the uses of that parameter for multi-step screening procedures to search for conserved secondary structures and for assigning confidence values to the predicted base pairs. The C++ source code that implements the McCaskill-MEA algorithm and the test dataset used in this paper are available at http://www.ncrna.org/papers/McCaskillMEA/. Supplementary data are available at Bioinformatics online.


In vivo evaluation for rhGM-CSF wound-healing efficacy in topical vehicles.
The wound-healing efficacy of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) was studied in a mouse model. Full-thickness wounds were treated with liquid crystalline, emulsion, and niosome vehicles alone and with rhGM-CSF. The control group was non-medicated. Observation of the vehicle groups with and without the rhGM-CSF displayed better healing profiles than the control group. The vehicles were also evaluated among themselves and it was noted that emulsion base and niosome base groups gave significantly better healing profiles and histological results than the liquid crystalline base group. Among the rhGM-CSF containing groups, emulsion formulation displayed a stronger wound-healing effectiveness compared to the other formulations. In vitro release characteristics of the recombinant protein from the three vehicle formulations were demonstrated with diffusion cells. Histological and immunohistochemical evaluation was performed on biopsies taken on the last day of the experiment.


Predicting a beneficial response to motor control training in patients with low back pain: a longitudinal cohort study.
Exercise therapy such as motor control training (MCT) has been shown to reduce pain and disability in people with low back pain (LBP). It is unknown which patients are most likely to benefit. This longitudinal cohort study aimed to: (1) retrospectively examine records from a large cohort of patients who received MCT treatment, (2) identify potentially important predictors of response to MCT and (3) test the predictors on an independent (split) sample derived from the original cohort of patients, using one group to identify the predictors and the other to test them. The response of 775 patients with LBP to MCT was classified as 'improved' or 'not improved' based on self-reported change in pain levels and symptoms. Measures were examined for associations with improvement and entered into a logistic regression model to classify patients as low, medium or high benefits of improvement with MCT. The model was tested on an independent sample. A positive response was seen in patients with: no evidence of scoliosis [OR = 4.0, 95% CI (1.7, 9.6)], LBP without associated groin pain [OR = 2.2, 95% CI (1.0, 5.0)], LBP which was chronic recurrent in nature [OR = 3.1, 95% CI (1.8, 5.3)] and poor results on muscle testing of the multifidus muscle [OR = 2.0, 95% CI (1.1, 3.7)]. Testing on an independent sample confirmed that patients could be classified into benefit groups. This study provides a first step towards assisting clinicians to select patients most likely to respond to MCT. These slides can be retrieved under Electronic Supplementary Material.


[Prevalence of antimicrobial resistance in enterococci isolated from blood in Madrid (1994-1995)].
The aim of this study was to evaluate the antimicrobial resistance of enterococci isolated from blood samples in three hospitals in Madrid (Spain) from 1994 to 1995. One hundred strains, 83 Enterococcus faecalis, 15 E. faecium, and 2 E. durans, isolated from January 1994 to April 1995 were studied. The minimum inhibitory concentrations (MIC) of 11 antimicrobians were determined by the agar dilution method. Four percent of the strains were resistant to ampicillin and 7% to penicillin. Ninety-two percent were sensitive to vancomycin. The percentage of strains with a high level of resistance (HLR) to some aminoglucoside was 60%. HLR was observed to gentamycin in 41%, to streptomycin in 46% and to kanamycin in 58% of the strains. Half of the isolates were resistant to the fluoroquinolones tested. HLR was significantly associated with aminoglucosides with HLR (MIC > or = 16 mg/l) to fluoroquinolones in the strains studied (p < 0.001). The incidence of resistance to ampicillin and vancomycin is low and very high to aminoglucosides and fluoroquinolones. There is also a very significant association between HLR to fluoroquinolones and HLR to aminoglucosides.


Granulocyte colony-stimulating factor-induced blood stem cell mobilisation in patients with chronic heart failure--Feasibility, safety and effects on exercise tolerance and cardiac function.
Bone marrow-derived stem cells may contribute to the regeneration of non-haematopoietic organs. In order to test whether an increase in circulating stem cell numbers improves impaired myocardial function we treated 16 male patients with chronic heart failure due to dilated (DCM; n = 7) or ischaemic cardiomyopathy (ICM; n = 9) with the stem cell mobilising cytokine granulocyte colony-stimulating factor (G-CSF; four 10-day treatment periods interrupted by treatment-free intervals of equal length). Safety and efficacy analyses were performed at regular intervals. Peak CD34+ cell counts remained constant from cycle to cycle. Cardiac side effects in ICM patients included occasional episodes of dyspnea or angina and one episode of fatal ventricular fibrillation. Nine (4 DCM, 5 ICM) of 12 patients receiving four full G-CSF cycles experienced an improvement by one New York Heart Association (NYHA) class and a statistically significant increase in six-minute walking distance. By contrast, none of 8 ICM historical controls had a change in NYHA class during a similar time period. Statistically significant changes in echocardiographic parameters were not recorded. Sequential administration of G-CSF is feasible and possibly effective in improving physical performance in patients with chronic heart failure. Patients with ICM may be at risk of increased angina and arrhythmias.


Drug-related disorders and the criminal and clinical background of the prison population of São Paulo State, Brazil.
To analyze the association between drug (DAD) and alcohol (AAD) abuse and dependency and criminal and clinical background by gender of prisoners in São Paulo, Brazil. Cross-sectional study, random sample stratified by administrative district, from which prisons and prisoners were selected via random, multistage sampling. Psychiatric diagnoses were made with the CIDI 2.1. Lifetime prevalence and 95% CI were calculated and adjusted via analysis of complex samples. Multinomial logistic regression analysis was carried out with four categories of dependent variables: presence AAD; presence DAD; presence of another mental disorder; no mental disorders. For female alcohol and drug abuse and dependency (ADAD) were combined into a single category. The sample was composed by 1809 interviewed prisoners (1192 men and 617 women). Prevalence of DAD and AAD was 25.2% and 15.6%, respectively, among female prisoners, and 26.5% and 18.5% among males. Male prisoners with DAD were more likely to have a criminal record as an adolescent (OR 2.17), to be a repeat offender (OR 2.85), and to have committed a property crime (OR 2.18). Prisoners with AAD were repeat offenders (OR 2.18). Among female prisoners, ADAD was associated with repeat offenses (OR 3.39), a criminal record as an adolescent (OR 9.24), a clinical or infectious condition (OR 5.09), another health problem (OR 3.04), and violent crime (OR 2.5). The study confirmed an association between drug-use disorders and the criminal and clinical background in the study population. Prisoners with such disorders were more likely to be repeat offenders and to have a criminal record as adolescents. Among female prisoners disorders were also associated with violent crime and health problems, while among males they were associated with property crime. These patterns in clinical and criminal backgrounds illustrate the need for social rehabilitation programs and specific medical treatment for prison populations.


The effect of heterologous insertions on gene conversion in mitotically dividing cells in Drosophila melanogaster.
We examined the influence that heterologous sequences of different sizes have on the frequency of double-strand-break repair by gene conversion in Drosophila melanogaster. We induced a double-strand break on one X chromosome in female flies by P-element excision. These flies contained heterologous insertions of various sizes located 238 bp from the break site in cis or in trans to the break, or both. We observed a significant decrease in double-strand-break repair with large heterologous insertions located either in cis or in trans to the break. Reestablishing the homology by including the same heterologous sequence in cis and in trans to the double-strand break restored the frequency of gene conversion to wild-type levels. In one instance, an allelic nonhomologous insertion completely abolished repair by homologous recombination. The results show that the repair of a double-strand break by gene conversion requires chromosome pairing in the local region of the double-strand break.


[Minimal cardiac surgery].
In general surgery, the aim of new techniques is to reduce the length of the skin incisions and/or to use endoscopic or laparoscopic instruments. The cardiac surgery makes not an exception. During the last two years, the material and the techniques are following a progressive evolution. Concerning the cardiac surgery of the adult, three techniques which are the mini-incision or thoracotomy and the surgery of the port-access are in full evolution. We describe the advantages and disadvantages.


Investigation of exercise intensity during a freestyle wrestling match.
This study investigated changes in exercise intensity during a freestyle wrestling match. Wrestling matches that consisted of three periods of 2 min were performed by nine elite collegiate male wrestlers. Exercise intensity was measured using heart rate (HR), blood lactate concentration ([BLa-]), and rating of perceived exertion (RPE). HR was continuously recorded during the match, and mean HR during each period was obtained. [BLa-] and RPE according to the 6-20-point Borg Perceived Exertion Scale were measured immediately after each period. HR during the wrestling match increased as a whole, but a continuous decrease in HR was observed during the first half of the second and third periods. This was likely caused by a cautious strategy involving reduced aggressive actions. HR significantly increased (P<0.05) from the first period (81 ± 6% of maximal HR [HRmax]) to the second period (88 ± 5% of HR(max)), and from the second to the third periods (92 ± 5% of HR(max)). [BLa-] significantly increased (P<0.05) from the first period (7.6 ± 2.0 mmol.L⁻¹) to the second period (10.4 ± 4.2 mmol.L⁻¹), but not from the second to the third periods (11.5 ± 3.1 mmol.L⁻¹). RPE significantly increased across the three periods (first, 13 ± 1; second, 15 ± 2; and third periods, 17 ± 2, P<0.05). Our results on changes in exercise intensity during each period and between periods would be helpful for making strategic decisions during wrestling matches and for planning daily training.


Outcomes of using endovascular aneurysm repair with active fixation in complex aneurysm morphology.
The ideal treatment option for patients with complex aneurysm morphology remains highly debated. The aim of this study was to investigate the impact of endovascular aneurysm repair (EVAR) with active fixation on outcomes in patients with complex aneurysm morphology. There were 340 consecutive patients who underwent EVAR using active fixation devices, 234 with active infrarenal fixation (AIF; Gore Excluder; W. L. Gore & Associates, Flagstaff, Ariz) and 106 with active suprarenal fixation (ASF; 85 Medtronic Endurant [Medtronic, Santa Rosa, Calif] and 21 Cook Zenith [Cook Medical, Bloomington, Ind]). Demographics, comorbidities, anatomic features, and outcomes were analyzed for patients receiving devices with active fixation. Outcomes of using active fixation in necks with <15-mm neck lengths, >60-degree infrarenal neck angle (β), >30-mm infrarenal neck diameter, severe aortic neck calcification or thrombus, and nonstraight neck morphology were evaluated. Of the 340 patients, 106 (78 men; mean age, 74.5 ± 9.3 years at the time of surgery) received implants with ASF and 234 (191 men; mean age, 74.6 ± 8.9 years at the time of surgery) received implants with AIF. In comparing AIF and ASF devices, patients in the suprarenal fixation group had significantly shorter follow-up time (25 ± 17 months vs 44.3 ± 32 months; P < .0001). Patients in the ASF group had shorter aortic neck lengths (25.5 ± 15.1 mm vs 28.6 ± 14.9 mm; P = NS) and significantly larger infrarenal neck diameters (25.9 ± 6.3 mm vs 23.4 ± 3.2 mm; P < .0001) and aneurysm diameters (59.9 ± 11.6 mm v. 55.9 ± 10.0 mm; P = .002). Outcomes were similar between groups, with no significant differences in reintervention, proximal endoleak, sac growth, abdominal aortic aneurysm-related death, or rupture. Of the complex anatomic neck features investigated, neck diameter >30 mm and nonstraight neck morphology had the highest rates of reintervention in ASF devices. In cases of hostile infrarenal neck morphology, ASF appears to be used more frequently. Our data suggest that ASF may be useful for certain patients but may be unfavorable for others, such as those with wide necks or several difficult neck features. Nevertheless, further research is needed to evaluate more optimal treatment options, such as fenestrated EVAR, branched EVAR, and endovascular adjuncts such as EndoAnchors (Aptus Endosystems, Sunnyvale, Calif), in dealing with high-risk anatomic characteristics that may not be optimally managed with standard EVAR devices with active fixation.


MAP4Ks inhibition promotes retinal neuron regeneration from Müller glia in adult mice.
Mammalian Müller glia (MG) possess limited regenerative capacities. However, the intrinsic capacity of mammalian MG to transdifferentiate to generate mature neurons without transgenic manipulations remains speculative. Here we show that MAP4K4, MAP4K6 and MAP4K7, which are conserved Misshapen subfamily of ste20 kinases homologs, repress YAP activity in mammalian MG and therefore restrict their ability to be reprogrammed. However, by treating with a small molecule inhibitor of MAP4K4/6/7, mouse MG regain their ability to proliferate and enter into a retinal progenitor cell (RPC)-like state after NMDA-induced retinal damage; such plasticity was lost in YAP knockout MG. Moreover, spontaneous trans-differentiation of MG into retinal neurons expressing both amacrine and retinal ganglion cell (RGC) markers occurs after inhibitor withdrawal. Taken together, these findings suggest that MAP4Ks block the reprogramming capacity of MG in a YAP-dependent manner in adult mammals, which provides a novel avenue for the pharmaceutical induction of retinal regeneration in vivo.


Improving symptom communication through personal digital assistants: the CHAT (Communicating Health Assisted by Technology) project.
Communication problems impede effective symptom management during chemotherapy. The primary aim of this pilot randomized controlled trial was to test the effects of a personal digital assistant-delivered communication intervention on pain, depression, and fatigue symptoms among breast cancer patients undergoing chemotherapy. Secondary aims included assessment of 1) study feasibility, 2) patient and clinician responses to study participation, and 3) intervention effects on health-related quality of life (HRQoL) and communication self-efficacy. Intervention group participants (n = 27) completed symptom inventories at baseline, once per week during treatment, and at posttreatment. Depending on symptom severity, they viewed race-concordant videos on how to communicate about pain, depression and/or fatigue, using the personal digital assistant. Symptom records were tracked and shared with clinicians. Control group participants (n = 23) received usual care. Longitudinal random effects modeling assessed the changes in average symptom scores over time. Descriptive statistics assessed study feasibility and intervention effects on HRQoL and communication self-efficacy. Postintervention focus groups, interviews, and surveys assessed responses to study participation. Mean age of the participants was 51.0 years; 42 participants (84%) were white. In comparison with control, intervention group participants reported lower average pain severity over time (P = .015). Mean pain interference scores over time were marginally different between groups (P = .07); mean depression and fatigue scores over time were statistically nonsignificant. Feasibility outcomes and perspectives about study participation were positive. Mean pre-post decreases in HRQoL were generally higher among intervention group participants; pre-post changes in communication self-efficacy were equivalent. Mixed findings of the study indicate the need for future research.


A Novel Germline Pathogenic Variant of RECQL4 Gene in an Iranian Pedigree with Familial Squamous Cell Carcinoma: A Brief Report.
Squamous cell carcinoma (SCC) is the most common human solid tumor and the leading cause of cancer death. SCC of the breast is a very rare type of cancer that has not been well researched. Early identification of the genetic factors involved can lead to early diagnosis and targeted treatment. The present study was conducted in 2018 at Isfahan University of Medical Sciences (Isfahan, Iran). The proband was a 66-year-old woman with SCC of the breast and a positive family history of cancer. Blood DNA samples were used for whole-exome sequencing to identify germline pathogenic variants. Variant annotation and prioritization were done on variant call format files using bioinformatics software tools. The screened variants were confirmed using the Sanger sequencing method. Co-segregation analysis was performed on the blood DNA samples of the first- and second-degree relatives of the proband to assess the presence of the mutation. A novel germline pathogenic variant was identified in the RECQL4 gene of the family. RECQL4 is a known protein in DNA repair and replication. Considering its effect on other types of SCC, it may play an important role in SCC initiation and progression in the breast.


Tumor necrosis factor-alpha stimulates gastric epithelial cell proliferation.
TNF-alpha is a cytokine produced during gastric mucosal injury. We examined whether TNF-alpha could promote mucosal repair by stimulation of epithelial cell proliferation and explored further the underlying mechanisms in a rat gastric mucosal epithelial cell line (RGM-1). TNF-alpha treatment (1-10 ng/ml) for 12 or 24 h significantly increased cell proliferation but did not induce apoptosis in RGM-1 cells. TNF-alpha treatment significantly increased cytosolic phospholipase A(2) and cyclooxygenase-2 (COX-2) protein expression and PGE(2) level but did not affect the protein levels of EGF, basic fibroblast growth factor, and COX-1 in RGM-1 cells. The mRNA of TNF receptor (TNF-R) 2 but not of TNF-R1 was also increased. Dexamethasone dose dependently inhibited the stimulatory effect of TNF-alpha on cell proliferation, which was associated with a significant decrease in cellular COX-2 expression and PGE(2) level. A selective COX-2 inhibitor 3-(3-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-5,5-dimethyl-(5)H-furan-2-one (DFU) by itself had no effect on basal cell proliferation but significantly reduced the stimulatory effect of TNF-alpha on RMG-1 cells. Combination of dexamethasone and DFU did not produce an additive effect. PGE(2) significantly reversed the depressive action of dexamethasone on cell proliferation. These results suggest that TNF-alpha plays a regulatory role in epithelial cell repair in the gastric mucosa via the TNF-alpha receptor and activation of the arachidonic acid/PG pathway.


Direct operation versus ICD therapy for ischemic ventricular tachycardia.
Now that the implantable cardioverter defibrillator is available as a therapeutic option for the management of ventricular tachycardia (VT), some argue that there no longer should be a role for direct surgical intervention for this malignant arrhythmia. Rebuttal of this argument is difficult for the following reasons: (1) there are many patients who are candidates for implantable cardioverter defibrillator therapy but not for direct VT operation, and thus direct comparisons of the two therapies is difficult; (2) implantable cardioverter defibrillator therapy by definition is palliative, but a VT operation is curative in most instances; (3) in many electrophysiologic triage algorithms, implantation of a cardioverter defibrillator and VT operation are employed as alternative, not competitive, therapies, again making direct comparisons difficult; and (4) probably most importantly, there are misconceptions in the literature regarding the risks and benefits of direct VT surgical procedures as they are currently performed. In this brief review, we examine the currently available data on both sides of this argument.


Management of severe acute exacerbations of COPD: an updated narrative review.
Patients with chronic obstructive pulmonary disease (COPD) may experience an acute worsening of respiratory symptoms that results in additional therapy; this event is defined as a COPD exacerbation (AECOPD). Hospitalization for AECOPD is accompanied by a rapid decline in health status with a high risk of mortality or other negative outcomes such as need for endotracheal intubation or intensive care unit (ICU) admission. Treatments for AECOPD aim to minimize the negative impact of the current exacerbation and to prevent subsequent events, such as relapse or readmission to hospital. In this narrative review, we update the scientific evidence about the in-hospital pharmacological and non-pharmacological treatments used in the management of a severe AECOPD. We review inhaled bronchodilators, steroids, and antibiotics for the pharmacological approach, and oxygen, high flow nasal cannulae (HFNC) oxygen therapy, non-invasive mechanical ventilation (NIMV) and pulmonary rehabilitation (PR) as non-pharmacological treatments. We also review some studies of non-conventional drugs that have been proposed for severe AECOPD. Several treatments exist for severe AECOPD patients requiring hospitalization. Some treatments such as steroids and NIMV (in patients admitted with a hypercapnic acute respiratory failure and respiratory acidosis) are supported by strong evidence of their efficacy. HFNC oxygen therapy needs further prospective studies. Although antibiotics are preferred in ICU patients, there is a lack of evidence regarding the preferred drugs and optimal duration of treatment for non-ICU patients. Early rehabilitation, if associated with standard treatment of patients, is recommended due to its feasibility and safety. There are currently few promising new drugs or new applications of existing drugs.


Alteration of the DNA damage response in colorectal tumor progression.
Recent studies have demonstrated increased levels of DNA double-strand breaks (DSBs) and activation of the DNA damage response (DDR) in precancerous lesions during cancer development. Those observations have not been fully elucidated using paraffin-embedded tissues of colorectal tumors. The aims of this study were to analyze the presence of DSBs and DDR activation mediated by p53-binding protein 1 (53BP1), which is a conserved checkpoint and DNA repair protein, and to clarify their association with colorectal tumor progression. We used immunohistochemical staining to investigate the expression of γH2AX, a sensitive marker for DSBs, in 152 colorectal tumors (46 low-grade adenomas, 25 high-grade adenomas, 25 intramucosal carcinomas, and 56 invasive carcinomas). The colocalization of γH2AX and 53BP1, which is strongly associated with the DSB repair process, was analyzed using double-label immunofluorescence. Elevated γH2AX expression was identified in 16 (16.7%) of 96 intramucosal neoplasias and in 19 (33.9%) of 56 invasive carcinomas. Double-label immunofluorescence occasionally revealed cells, particularly in invasive carcinoma, with γH2AX foci that did not colocalize with 53BP1. The percentage of tumor cells with γH2AX foci that colocalized with 53BP1 was significantly lower in invasive carcinoma than in intramucosal neoplasia (median percentage, 54.8% and 88.5%, respectively; P = .001). In conclusion, the number of cells with DSBs increases in intramucosal neoplasia and invasive carcinoma. The decreasing number of cells with colocalization of γH2AX and 53BP1 during the progression from intramucosal neoplasia to invasive carcinoma suggests that DDR, at least mediated by 53BP1, is inefficient during the process of cancer invasion.


Antiviral activity of Norakin (triperiden) and related anticholinergic antiparkinsonism drugs.
In view of the coincidence of antiviral and antiparkinsonism activities of amantadine four antiparkinsonism drugs, NorakinR (triperiden), ParkopanR (trihexyphenidyl), AntiparkinR (diethylbenzhydramine) and AkinetonR (biperiden) were tested for antiviral activity in various virus-cell systems. Norakin inhibited the replication of influenza A viruses in chick embryo fibroblast, MDCK and Ehrlich ascites tumour cells. It also inhibited the replication of measles virus in Vero cells, 50% inhibitory concentrations being 2-6 micrograms/ml. The drugs were also active against influenza B virus. Several representatives of other virus families, e.g. vaccinia, vesicular stomatitis, polio type 1 and herpes simplex type 1 viruses were insensitive to the compounds.


The sum of us: considerations on physician-industry relationships.
This essay describes critically the physician-industry relationships and how the latter influences economically in the realization of continuing medical education (CME), industry expenses in sponsoring the academic events of medical societies, travel costs and enrollment, payment for consultants and speakers. It also refers to the movements that have been created in the academic world to counteract this influence, such as No Free Lunch (Spanish version "NoGracias") and PharmFree. And the struggles between major scientific medical journals, with editorials and among editorialists on the concept of conflicts of interest. All this seen through the existence of an academic institution in Mexico and the exemplary life of one of its members.


Power to detect higher-order epistatic interactions in a metabolic pathway using a new mapping strategy.
Epistatic interactions among quantitative trait loci (QTL) contribute substantially to the variation in complex traits. The main objectives of this study were to (i) compare three- vs. four-step genome scans to identify three-way epistatic interactions among QTL belonging to a metabolic pathway, (ii) investigate by computer simulations the power and proportion of false positives (PFP) for detecting three-way interactions among QTL in recombinant inbred line (RIL) populations derived from a nested mating design, and (iii) compare these estimates to those obtained for detecting three-way interactions among QTL in RIL populations derived from diallel and different partial diallel mating designs. The single-nucleotide polymorphism haplotype data of B73 and 25 diverse maize inbreds were used to simulate the production of various RIL populations. Compared to the three-step genome scan, the power to detect three-way interactions was higher with the four-step genome scan. Higher power to detect three-way interactions was observed for RILs derived from optimally allocated distance-based designs than from nested designs or diallel designs. The power and PFP to detect three-way interactions using a nested design with 5000 RILs were for both the 4-QTL and the 12-QTL scenario of a magnitude that seems promising for their identification.


[Advances on the determination of resistant starch].
The present situation and prospect of studies on resistant starch home and abroad are introduced briefly and systemically. The determination of resistant starch should reflect the real condition in humans. The optimal method in vitro may be chosen by comparing the data from the ileac effluence using ileostomy. The intention is to measure the content of resistant starch in familiar food and supply the base for the dietary intake of resistant starch in humans.


Fine-scale movements of the Broadnose Sevengill shark and its main prey, the Gummy shark.
Information on the fine-scale movement of predators and their prey is important to interpret foraging behaviours and activity patterns. An understanding of these behaviours will help determine predator-prey relationships and their effects on community dynamics. For instance understanding a predator's movement behaviour may alter pre determined expectations of prey behaviour, as almost any aspect of the prey's decisions from foraging to mating can be influenced by the risk of predation. Acoustic telemetry was used to study the fine-scale movement patterns of the Broadnose Sevengill shark Notorynchus cepedianus and its main prey, the Gummy shark Mustelus antarcticus, in a coastal bay of southeast Tasmania. Notorynchus cepedianus displayed distinct diel differences in activity patterns. During the day they stayed close to the substrate (sea floor) and were frequently inactive. At night, however, their swimming behaviour continually oscillated through the water column from the substrate to near surface. In contrast, M. antarcticus remained close to the substrate for the entire diel cycle, and showed similar movement patterns for day and night. For both species, the possibility that movement is related to foraging behaviour is discussed. For M. antarcticus, movement may possibly be linked to a diet of predominantly slow benthic prey. On several occasions, N. cepedianus carried out a sequence of burst speed events (increased rates of movement) that could be related to chasing prey. All burst speed events during the day were across the substrate, while at night these occurred in the water column. Overall, diel differences in water column use, along with the presence of oscillatory behaviour and burst speed events suggest that N. cepedianus are nocturnal foragers, but may opportunistically attack prey they happen to encounter during the day.


In vivo confocal microscopic evaluation of langerhans cell density and distribution in the corneal epithelium of healthy volunteers and contact lens wearers.
To examine and compare the density and distribution of Langerhans cells (LCs) in the corneal epithelium of healthy volunteers and contact lens wearers. A total of 225 eyes of 130 healthy volunteers (age, 17-81 years) without history of ocular inflammation, trauma, or surgery and 98 eyes of 55 contact lens wearers (age, 13-76 years) were examined in vivo with the combination of the Heidelberg Retina Tomograph II and in-house-invented Rostock Cornea Module. In healthy volunteers, in vivo confocal microscopy revealed LCs in 31% of all volunteers, with 37 of these 43 volunteers presenting LCs both in the center and the periphery of the cornea with densities of 34 +/- 3 and 98 +/- 8 cells/mm, respectively. In the group of contact lens wearers, 55% of all corneas presented with LCs, and 11 of these 33 corneas revealed LCs at central and peripheral locations. Although LC densities were markedly higher in both the central (78 +/- 25 cells/mm) and the peripheral cornea (210 +/- 24 cells/mm) of contact lens wearers, the gradient of LC density from peripheral to central cornea was found almost identical in both groups. In the central cornea, LC density decreased with duration of contact lens wear. LCs were located at the depth of 35 to 60 microm (ie, the level of lower intermediate cells, basal cells, and subepithelial nervous plexus). LCs presented as either large cells bearing long processes or smaller cells lacking cell dendrites, most supposedly indicating mature and immature phenotype, respectively. In vivo confocal microscopy enables evaluation of LC density and distribution in corneal epithelium. LCs were found present both in the center and the periphery of the cornea without difference in distribution between healthy volunteers and contact lens wearers. However, contact lens wearers revealed almost twofold higher LC densities in both locations, implying chronic mechanical irritation of the cornea in response to the contact lens as foreign body. Taken together, analysis of LC using in vivo confocal microscopy provides helpful information for a better understanding of contact lens-disturbed ocular homeostasis.


Palliative care in Thailand.
In Thailand, several barriers exist that prevent people with life-limiting illnesses from accessing good-quality palliative care, namely: lack of palliative care providers; lack of training and education for the palliative care workforce; and issues with availability and distribution of opioids. Without palliative care, people suffer needlessly during the last months of their life. This paper gives an analysis of these issues and provides recommendations for clinical practice, research and health policy that may help to alleviate these issues.


Nigral degeneration in neuroacanthocytosis.
We counted nerve cells in different subregions of the substantia nigra in three patients with neuroacanthocytosis and compared the results with those of age-matched Parkinson's disease and control patients. Two patients with neuroacanthocytosis and clinical parkinsonism in life had a reduced neuronal density in the substantia nigra, while in a third patient without parkinsonism, this number was at the lower limit of the control range. In neuroacanthocytosis with parkinsonism and in Parkinson's disease, the ventrolateral region of the substantia nigra was most severely affected, although in neuroacanthocytosis cases, nigral neuronal loss was more widespread.


Placenta-on-a-Chip as an In Vitro Approach to Evaluate the Physiological and Structural Characteristics of the Human Placental Barrier upon Drug Exposure: A Systematic Review.
Quantification of fetal drug exposure remains challenging since sampling from the placenta or fetus during pregnancy is too invasive. Currently existing in vivo (e.g., cord blood sampling) and ex vivo (e.g., placenta perfusion) models have inherent limitations. A placenta-on-a-chip model is a promising alternative. A systematic search was performed in PubMed on 2 February 2023, and Embase on 14 March 2023. Studies were included where placenta-on-a-chip was used to investigate placental physiology, placenta in different obstetric conditions, and/or fetal exposure to maternally administered drugs. Seventeen articles were included that used comparable approaches but different microfluidic devices and/or different cultured maternal and fetal cell lines. Of these studies, four quantified glucose transfer, four studies evaluated drug transport, three studies investigated nanoparticles, one study analyzed bacterial infection and five studies investigated preeclampsia. It was demonstrated that placenta-on-a-chip has the capacity to recapitulate the key characteristics of the human placental barrier. We aimed to identify knowledge gaps and provide the first steps towards an overview of current protocols for developing a placenta-on-a-chip, that facilitates comparison of results from different studies. Although models differ, they offer a promising approach for in vitro human placental and fetal drug studies under healthy and pathological conditions.


A case of multidrug-resistant (MDR) tuberculosis with collapse of the left lung after hemoptysis.
An 82-year-old female was admitted to our hospital with multidrug-resistant (MDR) tuberculosis, defined as resistance to both isoniazid and rifampicin. Chest X-ray showed massive infiltrates with a large cavitary lesions in the left lung field. No antituberculous agents were useful in improving her clinical condition and at 6th months after admission, she exhibited sudden onset of massive hemoptysis, which was successfully treated by bronchial artery embolization. After hemoptysis, her chest X-ray showed collapse of the left lung and computed tomography showed a coagula-like shadow in the left main bronchus, and sputum examination revealed no Mycobacterium tuberculosis colonies. The patient was discharged 5 months after the onset of hemoptysis.


Synchronization of oxytocin neurons in suckled rats: possible role of bilateral innervation of hypothalamic supraoptic nuclei by single medullary neurons.
We have previously shown that oxytocin neurons located in the four hypothalamic magnocellular nuclei display synchronous bursts of action potentials before each milk ejection. The mechanisms involved in such a synchronization have, however, not yet been elucidated. In this study, we test the hypothesis of an extranuclear synchronization arising from a common extrahypothalamic input innervating bilateral magnocellular nuclei. First, two different retrograde tracers were injected into the right and left supraoptic nuclei of rats that were fixed 5-7 days later. Each tracer labelled numerous neurons in various brain regions ipsilateral or contralateral to the injection site, but colocalization of the two tracers within the same cell body could only be detected bilaterally in neurons in the ventromedial regions of the medulla oblongata. The axonal projections of these medullary neurons were then visualized by the unilateral microinjection of an anterograde tracer (BDA) within the ventromedial medulla oblongata. BDA-labelled axons afferent to the hypothalamus were found to branch towards both supraoptic nuclei through medial portions of the optic chiasma. Finally, in anaesthetized lactating rats, surgical lesions were placed medially through the optic chiasma and the electrical activity of oxytocin neurons in bilateral supraoptic nuclei was pair-recorded during suckling. The incidence of synchronous bursts in oxytocin neurons located within bilateral supraoptic nuclei were dramatically altered only when the medial portions of the optic chiasma were totally lesioned. Taken together, these data suggest that medullary neurons afferent to bilateral supraoptic nuclei are involved in the recruitment and synchronization of bursting in oxytocin neurons during suckling.


[Pre-analytical phase impact in the differences in natremia obtained by direct and indirect ion selective electrodes methods].
Natremia is an important biological parameter providing information on the hydration state of patient's intracellular sector. Its measurement can be carried out either by multiparametric laboratory analyser (indirect potentiometry) or delocalized biology analyser (direct potentiometry). The main problem is that for a same patient, these two analysers can give quite different results, hence inducing interpretation problems for clinician. Two one-week study periods comparing the variations in blood sodium levels produced by these automatic analysers were carried out in two intensive care units of Clermont-Ferrand University Hospital. During the second study period, a protocol for collecting blood samples was applied in order to improve the pre-analytical conditions. Between the two weeks of studies, the median of the differences in natremia was significantly reduced, going from 4 mmol/L to 2 mmol/L (p < 0.001), as was the proportion of patients with large differences in sodium levels (strictly higher than 3 mmol/L) going from 51% to 24.8% (p < 0.001). The patients still presenting large variations in sodium had a median of proteins significantly lower than patients with deviations less than or equal to 3 mmol/L: 58.1 g/L against 62.25 g/L respectively (p < 0.001) leading to pseudo-hypernatremia (indirect potentiometry). Despite a significant reduction in differences linked to the application of good preanalytical practices, some patients nonetheless presented a major difference in natremia due to the difference of technique (variations in the lipidoprotein phase of the plasma of intensive care patients) and to the measurement uncertainties.


Human bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues.
Adult neural crest stem-derived cells (NCSC) are of extraordinary high plasticity and promising candidates for use in regenerative medicine. Several locations such as skin, adipose tissue, dental pulp or bone marrow have been described in rodent, as sources of NCSC. However, very little information is available concerning their correspondence in human tissues, and more precisely for human bone marrow. The main objective of this study was therefore to characterize NCSC from adult human bone marrow. In this purpose, we compared human bone marrow stromal cells to human adipose tissue and dermis, already described for containing NCSC. We performed comparative analyses in terms of gene and protein expression as well as functional characterizations. It appeared that human bone marrow, similarly to adipose tissue and dermis, contains NESTIN+ / SOX9+ / TWIST+ / SLUG+ / P75NTR+ / BRN3A+/ MSI1+/ SNAIL1+ cells and were able to differentiate into melanocytes, Schwann cells and neurons. Moreover, when injected into chicken embryos, all those cells were able to migrate and follow endogenous neural crest migration pathways. Altogether, the phenotypic characterization and migration abilities strongly suggest the presence of neural crest-derived cells in human adult bone marrow.


Sensitive chemiluminescence detection of prion protein on a membrane by using a peroxidase-labeled dextran probe.
We synthesized dextran-based macromolecular probes carrying multiple molecules of horseradish peroxidase (HRP) as a signal-trigger enzyme and of biotin as an assembly mediator without losing the enzymatic activity. Multiple attachments of HRP and biotin to the dextran backbone were readily accomplished after the formation of aldehyde groups into the dextran macromolecule by periodate oxidation. The synthesized macromolecular probe was successfully used for sensitive chemiluminescence (CL)-imaging detection of mouse recombinant prion protein on a nylon membrane. The prion protein at a small amount of 20 fmol blotted on a nylon membrane was specifically detected, indicating at least a 10-times higher sensitivity than that of a conventional biotinylated HRP probe. Therefore, the synthesized dextran-based probes containing HRP and biotin should be used for the sensitive high-throughput analysis of various proteins on a solid-phase membrane.


Signal Quality Analysis of Single-Arm Electrocardiography.
The number of people experiencing mental stress or emotional dysfunction has increased since the onset of the COVID-19 pandemic, as many individuals have had to adapt their daily lives. Numerous studies have demonstrated that mental health disorders can pose a risk for certain diseases, and they are also closely associated with the problem of mental workload. Now, wearable devices and mobile health applications are being utilized to monitor and assess individuals' mental health conditions on a daily basis using heart rate variability (HRV), typically measured by the R-to-R wave interval (RRI) of an electrocardiogram (ECG). However, portable or wearable ECG devices generally require two electrodes to perform bipolar limb leads, such as the Einthoven triangle. This study aims to develop a single-arm ECG measurement method, with lead I ECG serving as the gold standard. We conducted static and dynamic experiments to analyze the morphological performance and signal-to-noise ratio (SNR) of the single-arm ECG. Three morphological features were defined, RRI, the duration of the QRS complex wave, and the amplitude of the R wave. Thirty subjects participated in this study. The results indicated that RRI exhibited the highest cross-correlation (R = 0.9942) between the single-arm ECG and lead I ECG, while the duration of the QRS complex wave showed the weakest cross-correlation (R = 0.2201). The best SNR obtained was 26.1 ± 5.9 dB during the resting experiment, whereas the worst SNR was 12.5 ± 5.1 dB during the raising and lowering of the arm along the z-axis. This single-arm ECG measurement method offers easier operation compared to traditional ECG measurement techniques, making it applicable for HRV measurement and the detection of an irregular RRI.


Differential impact of body position on the severity of disordered breathing in heart failure patients with obstructive vs. central sleep apnoea.
Obstructive (OSA) and central sleep apnoea (CSA) are a common comorbidity in patients with heart failure. The purpose of this study was to assess and compare the impact of body position on the severity of sleep apnoea in these two groups of patients. Standard polysomnography was performed in consecutive, clinically stable, optimally treated patients with moderate-to-severe heart failure and systolic dysfunction. Patients with an apnoea-hypopnoea index (AHI) ≥15/h (n = 120) were included in the study. The severity of sleep-disordered breathing was quantified by the AHI, the mean value of oxygen desaturations (O2 desat) and the apnoea ratio. Data from the right and left positions were combined into a single lateral position. Positional sleep apnoea was defined as a >50% reduction in the AHI between the supine and the lateral position. Twenty-nine and 91 subjects had dominant OSA and CSA, respectively. The AHI markedly decreased from the supine to the lateral position in both groups [OSA: (median [q1,q3]) 50.3 [36.9, 67.6]/h vs. 10.4 [7.0, 18.5]/h, P < 0.0001; CSA: 47.4 [37.6, 56.0]/h vs. 19.3 [11.9, 33.3]/h]. The reduction was greater in OSA patients (p = 0.027). Similarly, O2 desat and the apnoea ratio decreased in the lateral position (P < 0.0001). Positional sleep apnoea was observed in 76% of OSA and 53% of CSA patients (P = 0.028). This study demonstrates that the lateral sleeping position has a major beneficial effect on the severity of sleep-disordered breathing in heart failure patients, and that this improvement is greater in subjects with OSA than in those with CSA.


Respiratory symptoms and illnesses related to the concentration of airborne particulate matter among brick kiln workers in Kathmandu valley, Nepal.
Bricks have been manufactured in Nepal for hundreds of years and are seen as a component of Nepalese sculpture and architecture. Large quantities of hazardous materials including high concentrations of particulate matter are emitted on a daily basis from brick kilns. Exposure to these hazardous materials can lead to adverse consequences on the environment and human health. This study was conducted to estimate the prevalence of respiratory symptoms/illnesses and the magnitude of respirable and total dust exposures among Nepalese brick kiln workers. Respiratory symptoms/illnesses were evaluated by questionnaire among brickfield workers (n = 400) and a referent group of grocery workers (n = 400) in Kathmandu valley. Work zones (WZs): green brick molding (GBM), green brick stacking/carrying (GBS/C), red brick loading/carrying (RBL/C), coal preparation (CP) and firemen (FM) were the similar exposure groups (SEGs) from where personal air samples and interviews were taken. Among brickfield workers, personal monitoring was conducted across SEGs for total (n = 89) and respirable (n = 72) dust during February-March 2015 and March-April 2016. Applying multi-stage probability proportionate to size sampling technique, 16 kilns and 400 brick workers for interview were selected. Proportions, means, medians and ranges were calculated for the demographics, samples and respiratory symptoms/illnesses. One-way ANOVA was applied to compare the significance differences of the level of particulate matter among SEGs. Bivariate and multivariate logistic regression analysis were performed to evaluate association between respiratory symptoms/illnesses and participants groups, and SEGs among brick kiln workers at 0.05 level. Statistical analyses were performed using IBM SPSS Statistics 21. Chronic cough (14.3%), phlegm (16.6%) and bronchitis (19.0%) were higher (P < 0.05) among brickfield compared with grocery workers (6.8, 5.8 and 10.8%). Mean respirable (5.888 mg/m3) and total (20.657 mg/m3) dust exposures were highest for red brick loading tasks. The prevalence of chronic cough, chronic phlegm, chronic bronchitis, wheezing and asthma were significantly higher for other WZs workers (p < 0.05) compared with CP; for GBM: 22.9, 34.6, 15.0 and 7.5%; for GBS/C: 13.5, 15.8, 10.0, 8.8 and 7.5%; for RBL/C: 11.1, 17.1, 27.4, 19.0 and 11.9%; for FM: 18.4, 12.5, 28.4, 4.9 and 0.0%; and for CP: 4.9, 6.3, 13.3, 9.3 and 4.0% respectively. High dust exposures identified in this study may explain the increased prevalence of respiratory symptoms/illnesses among Nepalese brickfield workers, warranting action to reduce exposures.


Clinical Efficacy of Pre-Hospital Electrocardiogram Transmission in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.
Rapid reperfusion by primary percutaneous coronary intervention (pPCI) is an established strategy for the treatment of patients with ST-segment elevation myocardial infarction (STEMI). Pre-hospital electrocardiogram (PH-ECG) transmission by the emergency medical services (EMS) facilitates timely reperfusion in these patients. However, evidence regarding the clinical benefits of PH-ECG in individual hospitals is limited.This retrospective, observational study investigated the clinical efficacy of PH-ECG in STEMI patients who underwent pPCI. Of a total of 382 consecutive STEMI patients, 237 were enrolled in the study and divided into 2 groups: a PH-ECG group (n = 77) and non-PH-ECG group (n = 160). Door-to-balloon time (D2BT) was significantly shorter in the PH-ECG group (66 [52-80] min), compared to the non-PH-ECG group (70 [57-88] minutes, P = 0.01). The 30-day all-cause mortality rate was 6% in the PH-ECG group, which was significantly lower than that in the non-PH-ECG group (16%) (P = 0.037, hazard ratio [HR]: 0.38, 95% CI: 0.15-0.98). This trend was particularly evident in severely ill patients when stratified by GRACE score.The use of PH-ECG improved the survival rate of STEMI patients undergoing pPCI due to the improved pre-arrival preparation based on the EMS information. Coordination between EMS and PCI-capable institutes is essential for the management of PH-ECG.


Should ethanol be scheduled as a drug of high risk to public health?
Six criteria described in the New Zealand Misuse of Drugs Act and used by the Expert Advisory Committee on Drugs (EACD) for determining the risk of a drug to public health were examined in relation to ethanol, using gamma-hydroxybutyric acid (GHB) as a comparator drug. GHB is an ideal candidate for use as a comparator because it is a sedative substance very similar to ethanol and has been previously investigated by the EACD using these six criteria. GHB was subsequently classified as a Class B1 drug under the Misuse of Drugs Act, that is, as a prohibited drug of high risk to public health. The dangerousness level of ethanol was found to be at least similar to that of GHB in this analysis. This highlights a major discrepancy in public policy.


A new strategy for enhancing the oral bioavailability of drugs with poor water-solubility and low liposolubility based on phospholipid complex and supersaturated SEDDS.
A novel supersaturated self-emulsifying drug delivery system (Super-SEDDS) loaded with scutellarin-phospholipid complex (SPC) was developed. The system aimed to address the limitations presented by conventional SEDDS as delivery carriers for drugs with poor water-solubility, low liposolubility and high dose. As an intermediate, SPC was first prepared based on the response surface design. The presence of amorphous scutellarin was demonstrated through differential scanning calorimetry (DSC) and X-ray diffraction (XRD), while enhanced liposolubility was confirmed through comparison with scutellarin powder via an octanol/water distribution test. On the basis of the solubility study and ternary phase diagram, Super-SEDDS containing SPC of up to 200% equilibrium solubility (Seq) was designed, which composed of ethyl oleate, Cremophor RH40 and Transcutol HP with a ratio of 60:25:15 (w/w%). The subsequent in vitro lipolysis study and ex vivo intestinal absorption test indicated that Super-SEDDS enhanced the cumulative dissolution from 70% to 100% and improved the intestinal absorption from 0.04 to 0.12 µg/cm(2) compared with scutellarin powder. Furthermore, an in vivo study demonstrated that Super-SEDDS achieved the AUC0-t of scutellarin up to approximate 1.7-fold as scutellarin powder. It was also proved superior to SPC and the conventional SEDDS. Super-SEDDS showed great potential for expanding the usage of SEDDS and could act as an alternative to conventional SEDDS.


Prognosis of gestational choriocarcinoma at Khyber Teaching Hospital Peshawar.
Choriocarcinoma is a highly malignant tumour which originates in developing trophoblast of pregnancy, most commonly following molar pregnancy. It is a potentially fatal disease, but current management protocols have turned the prognosis highly favourable. This study was done on patients with gestational choriocarcinoma presenting to Gynae-B unit of Khyber Teaching Hospital Peshawar, between May, 1996 to December, 1997, diagnosed on the basis of clinical course and elevated level of HCG. Metastatic evaluation of the disease was done to assign different risk groups to the patients before selecting appropriate chemotherapy regimen for each patient. Results of the therapy were monitored by serial estimation of HCG levels. During this period 5 patients of choriocarcinoma were treated. In 2 (40%) cases choriocarcinoma developed after molar pregnancy whereas in 3 (60%) cases antecedent pregnancy resulted in spontaneous abortion. Four (80%) patients were from poor socioeconomic class, 3 (60%) were above 39 years of age and 4 (80%) were multiparous. Two patients (40%) were medium risk and 3 (60%) were high risk cases. There was no patient with low risk disease. EMA-CO (Etoposide, Methotrexate, Actinomycin-D, Cytocine, Oncovine) regimen was administered to all patients. Maximum number of cycles of chemotherapy given was 8. Only one patient developed drug resistance. Overall cure rate was 80% (4 patients survived out of 5 at two years' follow-up). Prognosis of gestational choriocarcinoma is favourable provided the appropriate therapy is administered early in the course of disease. Provision of free medical care should be considered for these patients to save their lives.


The ins and outs of collective bargaining.
Negotiation of a collective bargaining agreement requires knowledge and preparation. This article outlines considerations and strategies for nursing administrators who are about to participate in labor negotiations. A "how-to" focus is presented by the author, an attorney who represents major hospitals in labor negotiations.


Contrast-enhanced ultrasound evaluation of placental perfusion in brachicephalic bitches.
The present study aimed to investigate placental hemodynamics to determine quantitative and qualitative parameters for pregnant brachycephalic bitches as well as describe placental vascularization and perfusion in females with fetal abnormalities close to delivery. Forty-four healthy fetuses from 22 brachycephalic bitches and 9 fetuses with gestational abnormalities (anasarca and hydrocephalus) from 8 brachycephalic bitches were evaluated. All female dogs were artificially inseminated intravaginally and underwent cesarean section at the end of gestation. Pregnancy diagnosis was made on the 25th day and experimental evaluations were performed on Days 25 (M1), 45 (M2), and 58 (M3) of gestation in normal pregnancies. Fetuses with gestational abnormalities were evaluated at the last time point. Biometric values of the fetuses were determined by B-mode and vascular indices by Doppler fluxometry of the umbilical artery, whereas qualitative assessment of contrast filling and quantitative parameters of placental perfusion were performed using CEUS. Parameter comparisons among the examined fetuses (normal and abnormal) and between the moments (M1, M2, and M3) were performed by Student's t-test and ANOVA tests, and then correlated using the Spearman test. In healthy fetuses, systolic and diastolic velocities as well as the time averages of minimum and maximum velocities increased significantly from M2 to M3 (P < 0.05), whereas the pulsatility index (P < 0.043) and vascular resistance (P < 0.001) decreased. Contrast distribution was always homogeneous in placental tissues and CEUS filling parameters remained constant during the evaluated periods (P < 0.05). In fetuses with hydrops, Doppler values were similar to those obtained in healthy subjects (P > 0.05), but CEUS evaluation demonstrated a heterogeneous distribution with lower intensity of placental tissue filling and a delay in perfusion time (P < 0.05) with a diagnostic accuracy of 75%. The association of dopplerfluxometry and CEUS allowed evaluation of qualitative and quantitative parameters of physiological pregnancy hemodynamics in all gestational thirds without evidence of significant changes in the physiology of the maternal-fetal binomial, and CEUS was shown to be applicable in the detection of failures in placental vascular filling (tissue dysfunction) in fetuses with anasarca and hydrocephaly.


Mapping underwater sound noise and assessing its sources by using a self-organizing maps method.
This study aims to provide an objective mapping of the underwater noise and its sources over an Adriatic coastal marine habitat by applying the self-organizing maps (SOM) method. Systematic sampling of sea ambient noise (SAN) was carried out at ten predefined acoustic stations between 2007 and 2009. Analyses of noise levels were performed for 1/3 octave band standard centered frequencies in terms of instantaneous sound pressure levels averaged over 300 s to calculate the equivalent continuous sound pressure levels. Data on vessels' presence, type, and distance from the monitoring stations were also collected at each acoustic station during the acoustic sampling. Altogether 69 noise surveys were introduced to the SOM predefined 2 × 2 array. The overall results of the analysis distinguished two dominant underwater soundscapes, associating them mainly to the seasonal changes in the nautical tourism and fishing activities within the study area and to the wind and wave action. The analysis identified recreational vessels as the dominant anthropogenic source of underwater noise, particularly during the tourist season. The method demonstrated to be an efficient tool in predicting the SAN levels based on the vessel distribution, indicating also the possibility of its wider implication for marine conservation.


Effects of levosimendan on restrictive left ventricular filling in severe heart failure: a combined hemodynamic and Doppler echocardiographic study.
A restrictive pattern of left ventricular filling is often present in patients with severe heart failure. Although the hemodynamic effects of levosimendan have been studied, the effects of levosimendan on LV filling pattern have not been investigated. Pulsed-wave Doppler mitral (transthoracic) and pulmonary venous flow (transesophageal) velocity curves were recorded in 30 patients with a restrictive pattern of left ventricular filling with New York Heart Association class III or IV heart failure who had a documented left ventricular ejection fraction < 30% by echocardiography and received a 0.1 microg/kg/min infusion of levosimendan for 24 h. Levosimendan caused significant (p < 0.001) increases in stroke volume (from 46 +/- 4 to 57 +/- 4 mL) and decreases in pulmonary capillary wedge pressure (from 21 +/- 1 to 15 +/- 1 mm Hg). The E wave decreased (from 96 +/- 7 to 71 +/- 5 cm/s), and the A wave increased (from 40 +/- 4 to 46 +/- 4 cm/s). Moreover, deceleration time was increased (from 112 +/- 7 to 189 +/- 14 ms). The S wave of pulmonary venous flow was increased (from 38 +/- 3 to 60 +/- 3 cm/s), and atrial reversal was decreased (from 36 +/- 2 to 29 +/- 2 cm/s). All changes were significant (p < 0.001). Using stepwise linear regression analysis, we found that the percentage changes of the early/late transmitral diastolic peak flow velocity (E/A) ratio and the percentage changes of the isovolumetric relaxation time were independent predictors of the increase in cardiac output. Furthermore, the percentage changes of the systolic/diastolic ratio and the percentage changes of the E/A ratio were independent predictors of the decrease in pulmonary capillary wedge pressure. Treatment with levosimendan improved measures of left ventricular diastolic function. Consequently, left ventricular stroke volume was increased.


Uptake mechanisms for ascorbate and dehydroascorbate in lymphoblasts from diabetic nephropathy and hypertensive patients.
In diabetic nephropathy and hypertension, a major cause of mortality is from cardiovascular disease. Since low levels of antioxidants such as vitamin C have been associated with such complications, we have examined the uptake mechanisms for ascorbic acid (AA) and dehydroascorbic acid (DHA) in lymphoblasts from normal control subjects (CON), normoalbuminuric insulin-dependent diabetic (IDDM) patients (DCON), patients with IDDM and nephropathy (DN) and hypertensive patients (HT) using mass assays of uptake and measuring AA using high-performance liquid chromatography. Precautions were taken to prevent oxidation of AA and to take into account the instability of DHA in buffers. DHA uptake was the major mechanism in all four groups of subjects, and the Vmax (maximal uptake rate) was significantly lower in the DN cells (24.7 +/- 1.0 nmol [95% confidence intervals CI 22.5, 26.3] 10(6) cells(-1) h(-1)) compared to CON and DCON cells (33.9 +/- 2.1 [95% CI 29.4, 38.4] and 37.0 +/- 2.2 [95% CI 32.2, 41.8] nmol 10(6) cells(-1) h(-1), respectively, p < 0.001 for both). DHA Vmax was also lower in the HT group (23.2 +/- 1.1 [95% CI 20.7, 25.7] nmol 10(6) cells(-1) h(-1)) compared to the CON group (p < 0.001). There were no significant differences in the Km or passive membrane permeability for DHA or the AA uptake. DHA uptake showed a negative correlation to systolic blood pressure (r(s) = -0.49, p < 0.001). These findings suggest that impaired DHA uptake may be one component of the phenotype expressed by DN cells that may persist in culture. Impaired DHA uptake in vivo, especially in the presence of hyperglycaemia, leads to impaired regeneration of AA and depletion of anti-oxidant defences, exposing such individuals to increased risk of cardiovascular disease.


Curcumin, a compound with anti-inflammatory and anti-oxidant properties, down-regulates chemokine expression in bone marrow stromal cells.
Chemotactic cytokines or chemokines play an important role in the regulation of myelopoiesis. Since the production of chemokines and colony stimulating factors (CSFs) by bone marrow stromal cells requires inflammatory conditions, we investigated the effect of curcumin, an agent with anti-inflammatory and anti-oxidant activities, on the expression of monocyte chemoattractant protein-1 (MCP-1 or MCP-1/JE) and interferon inducible protein-10kD (IP-10) in mouse bone marrow stromal cell line +/+-1.LDA11. Both chemokines are readily expressed in stromal cells after stimulation with pro-inflammatory interleukin-1alpha (IL-1alpha), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and endotoxin lipopolysaccharide (LPS). Curcumin attenuates the levels of MCP-1/JE and IP-10 mRNA expression by all of these stimulatory agents. A detailed analysis of the regulatory effects of curcumin on chemokine expression by IL-1alpha was performed. Curcumin inhibits both chemokine mRNAs in a dose- and time-dependent manner. The suppressive effect of curcumin on both mRNAs is reversible with complete recovery from suppression within 24 hours after removal of curcumin. The suppression of mRNA by curcumin is dependent on de novo synthesis of an intermediary protein(s), since suppression is abrogated by concomitant treatment with cycloheximide (CHX). Destabilization of mRNA transcripts is not the mechanism by which curcumin lowers the levels of mRNA; however, transcripts formed in the presence of curcumin are more stable, as indicated by their slower degradation kinetics. Run-on transcriptional assays demonstrate that curcumin inhibits the transcriptional activity of both genes. Finally, the attenuation of chemokine gene expression is associated with decreased production of chemotactic activity. Together, these findings indicate that while curcumin may post-transcriptionally stabilize mRNA transcripts formed in its presence, the overall reduction in mRNA levels by curcumin is mediated by inhibition of the transcription of chemokine genes.


Competing selfish genetic elements in the butterfly Hypolimnas bolina.
Maternally inherited selfish genetic elements are common in animals . Whereas host genetics and ecology are recognized as factors that may limit the incidence of these parasites , theory suggests one further factor-interference with other selfish elements-that could affect their prevalence . In this paper, we show that spatial heterogeneity in the occurrence of the male-killing Wolbachia wBol1 in the tropical butterfly Hypolimnas bolina is caused by a second infection that can exclude the male-killer. We first provide evidence of a second Wolbachia strain, wBol2, present in most populations that do not carry the male-killer but rare or absent when the male-killer is present. Crossing data indicate that wBol2 in males induces cytoplasmic incompatibility to both uninfected and wBol1-infected females. The wBol2 infection can therefore not only spread through uninfected populations but also resist invasion by wBol1. Thus, we provide empirical support for the hypothesis that the incidence of particular selfish genetic elements can limit the presence of competing types.


Schistosoma haematobium infection, health and nutritional status in school-age children in a rural setting in Northern Senegal.
The aim of this study was to investigate the occurrence of urinary schistosomiasis in school children in a rural village of Northern Senegal, and to evaluate the impact of this parasitic infection on children's health, growth, and nutritional status. A cross-sectional survey was carried out on 465 children resident in the village of Kassak Nord, in Senegal, in an area which is highly endemic for Schistosoma haematobium. Data on health, nutritional status and urinary schistosomiasis were collected. The overall prevalence of urinary schistosomiasis in school children in Kassak was 47.4%. As for malnutrition, 29.7% of children were malnourished (BMI-for-age Z-score [BAZ] <-2) and 14.5% had a significant linear growth retardation (height-for-age Z-score [HAZ] <-2). Children with urinary schistosomiasis showed lower mean BAZ and HAZ than uninfected children (HAZ positives -0.7±1.4 vs. HAZ negatives -0.4±1.4, P=0.004; BAZ positives -1.5±1 vs. BAZ negatives -1.3±1.1, P=0.03). It was also found that infected children were at greater risk of malnutrition (BAZ<-2; OR 1.5; 95% CI 1.01-2.26). The results of this study support the hypothesis that urinary schistosomiasis affects negatively childhood health and nutritional status and are of importance for planning intervention aimed to monitoring and control Urinary Schistosomiasis and malnutrition.


Replication of mitochondrial DNA occurs by strand displacement with alternative light-strand origins, not via a strand-coupled mechanism.
The established strand-displacement model for mammalian mitochondrial DNA (mtDNA) replication has recently been questioned in light of new data using two-dimensional (2D) agarose gel electrophoresis. It has been proposed that a synchronous, strand-coupled mode of replication occurs in tissues, thereby casting doubt on the general validity of the "orthodox," or strand-displacement model. We have examined mtDNA replicative intermediates from mouse liver using atomic force microscopy and 2D agarose gel electrophoresis in order to resolve this issue. The data provide evidence for only the orthodox, strand-displacement mode of replication and reveal the presence of additional, alternative origins of lagging light-strand mtDNA synthesis. The conditions used for 2D agarose gel analysis are favorable for branch migration of asymmetrically replicating nascent strands. These data reconcile the original displacement mode of replication with the data obtained from 2D gel analyses.


Collapses and explosions in self-gravitating systems.
Collapse and explosion (reverse to collapse) transitions in self-gravitating systems are studied by molecular dynamics simulations. A microcanonical ensemble of point particles confined to a spherical box is considered. The particles interact via an attractive soft Coulomb potential. It is observed that a collapse indeed takes place when the energy of the uniform state is set near or below the metastability-instability threshold (collapse energy) as predicted by the mean-field theory. Similarly, an explosion occurs when the energy of the core-halo state is increased above the explosion energy, where according to the mean-field predictions the core-halo state becomes unstable. For systems consisting of 125-500 particles, the collapse takes about 10(5) single-particle crossing times to complete, while a typical explosion is by an order of magnitude faster. A finite lifetime of metastable states is observed. It is also found that the mean-field description of the uniform and core-halo states is exact within the statistical uncertainty of the molecular dynamics data.


Go in for the kill: How plants deploy effector-triggered immunity to combat pathogens. [Corrected].
Plant resistance (R) proteins perceive specific pathogen effectors from diverse plant pathogens to initiate defense responses, designated effector-triggered immunity (ETI). Plant R proteins are mostly nucleotide binding-leucine rich repeat (NB-LRR) proteins, which recognize pathogen effectors directly or indirectly through sophisticated mechanisms. Upon activation by effector proteins, R proteins elicit robust defense responses, including a rapid burst of reactive oxygen species (ROS), induced biosynthesis and accumulation of salicylic acid (SA), a rapid programmed cell death (PCD) called hypersensitive response (HR) at the infection sites, and increased expression of pathogenesis-related (PR) genes. Initiation of ETI is correlated with a complex network of defense signaling pathways, resulting in defensive cellular responses and large-scale transcriptional reprogramming events. In this review, we highlight important recent advances on the recognition of effectors, regulation and activation of plant R proteins, dynamic intracellular trafficking of R proteins, induction of cell death, and transcriptional reprogramming associated with ETI. Current knowledge gaps and future research directions are also discussed in this review.


Fractional quantum Hall state at nu=5/2 and the Moore-Read pfaffian.
Using exact diagonalization we show that the spin-polarized Coulomb ground state at nu=5/2 is adiabatically connected with the Moore-Read wave function for systems with up to 18 electrons on the surface of a sphere. The ground state is protected by a large gap for all system sizes studied. Furthermore, varying the Haldane pseudopotentials v{1} and v{3}, keeping all others at their value for the Coulomb interaction, energy gap and overlap between ground- and Moore-Read state form hills whose positions and extent in the (v{1},v{3}) plane coincide. We conclude that the physics of the Coulomb ground state at nu=5/2 is captured by the Moore-Read state. Such an adiabatic connection is not found at nu=1/2, unless the width of the interface wave function or Landau level mixing effects are large enough. Yet, a Moore-Read-phase at nu=1/2 appears unlikely in the thermodynamic limit.


Effect of anatomical fine structure on the dispersion of solutes in the spinal subarachnoid space.
The dispersion of a solute bolus is calculated for cerebrospinal fluid undergoing oscillatory flow in the subarachnoid space of the spine. The fine structure of the subarachnoid space (nerves and trabeculae) enhances both longitudinal and transverse dispersions five to ten times over a simple model with an open annular space. Overall, dispersion is >10(3) times simple molecular diffusion. The result of enhanced dispersion is rapid spread and dilution of the bolus, effectively stirred by fluid movement around the fine structure.


Morphometrics and behavior of a wild Asian elephant exhibiting disproportionate dwarfism.
Dwarfism is a condition characterized by shorter stature, at times accompanied by differential skeletal growth proportions relative to the species-typical physical conformation. Causes vary and are well-documented in humans as well as certain mammalian species in captive or laboratory conditions, but rarely observed in the wild. We report on a single case of apparent dwarfism in a free-ranging adult male Asian elephant in Sri Lanka, comparing physical dimensions to those of other males in the population as well as in previous literature. The subject M459 was found to have a shoulder height of approximately 195 cm, is shorter than the average height of typical mature males, with a body length of 218 cm. This ratio of body length to height deviates from what is typically observed, which is approximately 1:1, but was similar to the attributes of a dwarf elephant in captivity documented in 1955. We report on behavior including the surprising observation that M459 appears to have a competitive advantage in intrasexual contests. We discuss how this phenotype compares to cases of dwarfism in other non-human animals. M459 exemplifies a rare occurrence of disproportionate dwarfism in a free-ranging wild mammal that has survived to reproductive maturity and appears otherwise healthy.


Impact of Maternal Essential Fatty Acid Intake on the Birth Weight of Infants.
Increased uptake of essential fatty acids during pregnancy through seafood and supplementation has been shown to positively correlate with gestational age and increased infant birth weight. We aimed to evaluate the effect of maternal dietary intake of essential fatty acids, supplementation on gestational period and infant birth weight. A literature search with the help of various databases such as PubMed, Google Scholar, Web of Science and Scopus was conducted. Original research articles and intervention-based studies, which involve an association between dietary intake and supplementation of essential fatty acids during full-term pregnancy on human infant birth outcomes and published from 2011 to 2021, were included. In total, there were 21 intervention-based studies, including full-term pregnant women with or without existing comorbidities, which compared essential fatty acids in the form of dietary sources and supplementation with dietary counseling and with or without placebo. The intervention trials included in this review were conducted in developed and developing countries. Half of the pregnant women who enrolled in the study had comorbidities such as diabetes and hypertension, which might increase their risk of adverse maternal and infant birth outcomes. Most of the studies included in the review have reported a positive association between improvised dietary and supplementation intake of essential fatty acids with increased length of gestation, infant birth weight and other parameters such as head circumference, infant birth length and growth velocity. Positive correlations were found between increased consumption of essential fatty acids in food sources and supplements with improvised infant birth weight and gestational period.