High-frequency hearing impairment assessed with cochlear microphonics.
Cochlear microphonic (CM) measurements may potentially become a supplementary approach to otoacoustic emission (OAE) measurements for assessing low-frequency cochlear functions in the clinic. The objective of this study was to investigate the measurement of CMs in subjects with high-frequency hearing loss. Currently, CMs can be measured using electrocochleography (ECochG or ECoG) techniques. Both CMs and OAEs are cochlear responses, while auditory brainstem responses (ABRs) are not. However, there are inherent limitations associated with OAE measurements such as acoustic noise, which can conceal low-frequency OAEs measured in the clinic. However, CM measurements may not have these limitations. CMs were measured in human subjects using an ear canal electrode. The CMs were compared between the high-frequency hearing loss group and the normal-hearing control group. Distortion product OAEs (DPOAEs) and audiogram were also measured. The DPOAE and audiogram measurements indicate that the subjects were correctly selected for the two groups. Low-frequency CM waveforms (CMWs) can be measured using ear canal electrodes in high-frequency hearing loss subjects. The difference in amplitudes of CMWs between the high-frequency hearing loss group and the normal-hearing group is insignificant at low frequencies but significant at high frequencies.


High-frequency transformation of Rhizobium meliloti.
Transformation of R factor RP4 and its derivative pRK290 from Escherichia coli to Rhizobium meliloti is reported. The efficiency of transformation was in the range of 10(-5) per viable cell. In addition, chromosomal DNA prepared from one R. meliloti strain resistant to streptomycin was transferred to the isoleucine-valine-requiring mutant susceptible to streptomycin.


Dysphagia and dyspnea due to an anterior cervical osteophyte.
Hypertrophic anterior cervical osteophytes have been reported as a cause of dysphagia, with about 100 cases described in the literature; on the other hand, chronic or acute dyspnea due to edema of the laryngeal inlet or bilateral vocal cord adduction-fixation is rare. We report a 57-year-old patient with a 2-year history of dysphagia and episodic dyspnea, who suffered sudden, severe respiratory distress necessitating emergency tracheotomy. A voluminous anterior cervical osteophyte at the C5 level was diagnosed by computed tomography (CT) and barium swallow test and removed by an anterior approach to the cervical spine, with clinical remission. The incidence, pathogenetic mechanisms, radiological diagnosis, and surgical indications of anterior cervical osteophytes associated with dysphagia and dyspnea are discussed. We advise examining cervical spine patients with dysphagia and/or dyspnea by radiography and CT when other investigations are not conclusive for a digestive or respiratory pathology.


Steered Molecular Dynamics for Investigating the Interactions Between Insulin Receptor Tyrosine Kinase (IRK) and Variants of Protein Tyrosine Phosphatase 1B (PTP1B).
The aim of this study is to use steered molecular dynamics to investigate the dissociation process between IRK and PTP1Bs for wild type and five mutants (consisting of p.D181E, p.D181A, p.Q262A, p.D181A-Y46F, and p.D181A-Q262A). The gained results are observed not only the unbinding mechanism of IRK-PTP1B complexes came from pulling force profile, number of hydrogen bonds, and interaction energy between IRK and PTP1Bs but also described PTP1B's point mutations could variably change its binding affinity towards IRK. Additionally, the binding free energy calculated by Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) is also revealed that electrostatic energy and polar solvation energy mainly made up the binding free energy of PTP1B-IRK complexes.


Chemotherapy Pharmacodynamics and Neuroimaging and Neurocognitive Outcomes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia.
To examine associations among methotrexate pharmacodynamics, neuroimaging, and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy-only protocol. This longitudinal study linked pharmacokinetic assays collected during therapy to neurocognitive and brain imaging outcomes during long-term follow-up. A total of 218 (72.2%) of 302 eligible long-term survivors were recruited for outcome studies when they were more than 5 years post-diagnosis and older than 8 years of age. At long-term follow-up, survivors were an average of 13.8 years old and 7.7 years from diagnosis, and 51% were male. Neurocognitive testing, functional magnetic resonance imaging (MRI) during an executive function task, and structural MRI with diffusion tensor imaging were conducted. Generalized linear models were developed to identify predictors, and models were adjusted for age at diagnosis, sex, and parent education. Intelligence was within normal limits (mean, 98; standard deviation, 14) compared with population expectations (mean, 100; standard deviation, 15), though measures of executive function, processing speed, and memory were less than population means (all P < .02 after correction for false discovery rates). Higher plasma concentration of methotrexate was associated with a poorer executive function score (P < .02). Higher plasma methotrexate was also associated with higher functional MRI activity, with thicker cortices in dorsolateral prefrontal brain regions, and with white matter microstructure in the frontostriatal tact. Neurocognitive impairment was associated with these imaging findings as well. Associations did not change after adjustment for age or dose of leucovorin rescue. Survivors of childhood acute lymphoblastic leukemia treated on contemporary chemotherapy-only protocols demonstrate executive dysfunction. A higher plasma concentration of methotrexate was associated with executive dysfunction as well as with a thicker cortex and higher activity in frontal brain regions, regions often associated with executive function.


[The experience of laparoscopic radical nephrectomy for renal tumors].
We evaluate the safety and feasibility of laparoscopic radical nephrectomy for renal tumors. Between September 1993 and October 2001, 18 patients with renal tumors underwent laparoscopic radical nephrectomy. The mean patient age was 57.1 years ranging from 36 to 78. Clinical stage was T1N0 in all patients. The mean tumor diameter was 4.0 cm ranging from 1.8 to 7.0. Laparoscopic radical nephrectomy was performed by using the transperitoneal anterior approach on 11 patients and retroperitoneal approach on 7 patients. The specimen was removed through an extended stab wound after blunt segmentation of renal parenchyma in a specimen bag (LapSac). The mean operative time was 405 (270-550) and 453 (325-635) min for the transperitoneal approach and retroperitoneal approach respectively, and the mean blood loss was 281 (52-700) and 223 (10-850) ml, respectively. There was an intraoperative complication of minor splenic injury in 2 patients receiving the transperitoneal approach, which was conservatively managed. Histopathology revealed renal cell carcinoma in 17 patients and renal oncocytoma in one patient. There was no recurrence with a mean follow-up of 28.9 months. Compared with 13 patients who underwent open radical nephrectomy during the same period, laparoscopic nephrectomy has a longer operative time (424 versus 214 min, p < 0.001), equal blood loss (259 versus 210 ml, p = 0.59), quicker resumption of ambulation (1.8 versus 2.5 days, p = 0.016) and food intake (1.4 versus 2.2 days, p = 0.003), shorter postoperative hospital stay (10.9 versus 18 days, p = 0.0016), and a tendency of less frequent analgesic requirements (1.9 versus 4.7 times, p = 0.09). Laparoscopic radical nephrectomy is a safe and useful surgery for renal tumors providing minimal invasiveness.


The Mechanisms and Boundary Conditions of Drug Memory Reconsolidation.
Drug addiction can be seen as a disorder of maladaptive learning characterized by relapse. Therefore, disrupting drug-related memories could be an approach to improving therapies for addiction. Pioneering studies over the last two decades have revealed that consolidated memories are not static, but can be reconsolidated after retrieval, thereby providing candidate pathways for the treatment of addiction. The limbic-corticostriatal system is known to play a vital role in encoding the drug memory engram. Specific structures within this system contribute differently to the process of memory reconsolidation, making it a potential target for preventing relapse. In addition, as molecular processes are also active during memory reconsolidation, amnestic agents can be used to attenuate drug memory. In this review, we focus primarily on the brain structures involved in storing the drug memory engram, as well as the molecular processes involved in drug memory reconsolidation. Notably, we describe reports regarding boundary conditions constraining the therapeutic potential of memory reconsolidation. Furthermore, we discuss the principles that could be employed to modify stored memories. Finally, we emphasize the challenge of reconsolidation-based strategies, but end with an optimistic view on the development of reconsolidation theory for drug relapse prevention.


Transplant tourism.
Because of the ongoing organ donor shortage, transplant tourism is occurring at an increasing rate both in the USA and abroad. To date, there have been little published data to help guide the programmatic philosophy of the USA transplant centers regarding transplant tourism. We summarize position statements from several transplant societies regarding transplant tourism and specifically transplantation occurring in China (because of the use of executed prisoners as organ donors). Transplant tourism is ever increasing and patients may be at risk for greater post-transplant morbidity as well as inadequate follow up care. Transplant centers require some guidance with regard of how to deal with these patients. Transplant tourism is an increasing reality facing the USA transplant centers. Most professional societies do not condone it yet cannot abrogate a physician's right to care for such patients. Ethical principles mandate transplant physicians provide adequate care for returning transplant tourists. Better ways of assessing the scope of the problem are necessary. Transplant tourism may exist because of the disparity between the need for organ donors and their availability and is thus is likely to continue into the future.


Two-tiered subdivision of atypia on urine cytology can improve patient follow-up and optimize the utility of UroVysion.
The annual incidence of urothelial carcinoma continues to increase, and it is projected that greater than 70,000 new cases will occur in the year 2015. However, as much as 23% of cytologic specimens will demonstrate some degree of atypia without meeting the criteria for urothelial carcinoma and thus will be reported as atypical. The authors conducted 2 laboratory information searches and 1 survey. In total, 311 patients who had atypical cytology-biopsy pairs available were identified from the initial data search. The second data search identified 942 patients who had fluorescence in situ hybridization (FISH) results available. There was fair agreement between FISH results and cytology results (κ = 0.34; 95% confidence interval, 0.27-0.41). The analysis did not reveal any benefits of using additional atypical subcategories beyond the 2 suggested in the literature. It was determined that 2 strategies would provide an optimal balance: standardizing patient management and facilitating the adoption of universally recognized templates. When combining cytology and the 2-tiered atypical classification system with FISH testing, a marked increase in sensitivity and an accompanying decrease in specificity were observed compared with either test individually. Thus, highly sensitive FISH testing may help to identify high-risk patients among those in the group with uncertain atypical findings.


Comparison of adverse perinatal outcomes after single-needle and double-needle CVS techniques.
To determine the impact of the chorion villus sampling (CVS) technique on adverse perinatal outcomes. In this case-control study, 412 women who underwent CVS at 11-14 weeks of gestation and 231 women who did not undergo any invasive procedure were retrospectively evaluated. The women in the CVS group were further divided into two groups according to the use of single-needle technique (n=148) vs. double-needle technique (n=264). The adverse outcomes were compared between controls and the two CVS groups, and regression analysis was used to determine the significance of independent contribution. The rate of preeclampsia for the control group was 2.2%, for the double-needle group was 3% and for the single-needle group was 8.1%. CVS with single-needle technique was found to be an independent and statistically significant risk factor for preeclampsia [odds ratio (OR)=2.1, 95% confidence interval (CI); 1.4-2.7, P=0.008]. The risk of preeclampsia after CVS appears to be increased with single-needle technique compared with double-needle technique.


Hematologic derangements in HIV/AIDS patients and their relationship with the CD4 counts: a cross-sectional study.
Hematologic abnormalities are the most common complications of human immunodeficiency virus (HIV) infection being more pronounced during the late stages of the disease, thereby indicating the progressive nature of the disease. Anemia is the most frequent hematologic abnormality in HIV. However, leukopenia, lymphopenia, and thrombocytopenia have also been observed. We undertook this study to evaluate the hematologic abnormalities in HIV patients and their relationship with the CD4 cell counts. This is an analytical cross-sectional study that was carried out among patients in Jammu, India for the three years from 2015 to 2018. Data collection pro-forma has two parts. Firstly, socio-demographic details such as age, gender, marital status, and occupation were noted. Secondly, investigations such as HIV testing, complete blood counts and CD4 counts were considered. The Statistical Package for Social Sciences (SPSS) software version 20 was used for data entry and analysis. One way analysis of variance (ANOVA) was applied as appropriate to examine differences between quantitative variables. Anaemia was present in 72.5% of cases in our study. Leukopenia, lymphopenia and thrombocytopenia were observed in 18.33%, 49.17%, and 15.83% of the cases, respectively. We found statistically significant relationships of anemia, absolute lymphocyte count, and thrombocytopenia with the CD4 counts (P<0.0001, =0.018 and =0.044, respectively). However, CD4 counts at the time of presentation were not significantly related to the total leukocyte count and absolute neutrophil count. Anemia was the most frequent hematologic abnormality in HIV patients followed by lymphopenia, leukopenia, and thrombocytopenia. A significant relationship was observed between the anemia, absolute lymphocyte count, and thrombocytopenia with the CD4 counts. We recommend routine hematologic investigations and timely treatment for all the hematologic derangements in HIV patients.


Dietary fats and prevention of type 2 diabetes.
Although type 2 diabetes is determined primarily by lifestyle and genes, dietary composition may affect both its development and complications. Dietary fat is of particular interest because fatty acids influence glucose metabolism by altering cell membrane function, enzyme activity, insulin signaling, and gene expression. This paper focuses on the prevention of type 2 diabetes and summarizes the epidemiologic literature on associations between types of dietary fat and diabetes risk. It also summarizes controlled feeding studies on the effects of dietary fats on metabolic mediators, such as insulin resistance. Taken together, the evidence suggests that replacing saturated fats and trans fatty acids with unsaturated (polyunsaturated and/or monounsaturated) fats has beneficial effects on insulin sensitivity and is likely to reduce risk of type 2 diabetes. Among polyunsaturated fats, linoleic acid from the n-6 series improves insulin sensitivity. On the other hand, long-chain n-3 fatty acids do not appear to improve insulin sensitivity or glucose metabolism. In dietary practice, foods rich in vegetable oils, including non-hydrogenated margarines, nuts, and seeds, should replace foods rich in saturated fats from meats and fat-rich dairy products. Consumption of partially hydrogenated fats should be minimized. Additional controlled, long-term studies are needed to improve our knowledge on the optimal proportion of different types of fats to prevent diabetes.


G-induced vestibular dysfunction ('the wobblies') among aerobatic pilots: a case report and review.
G-induced vestibular dysfunction (GIVD) is a condition well known to aircraft pilots who experience high positive and negative G loads during unlimited-aerobatic competitions and air-show demonstrations. After landing and walking from their aircraft, pilots with GIVD manifest an extremely unstable gait, which they call the wobblies. This article includes a report of one such case of GIVD, which to the author's knowledge is the first published case report of this condition in the medical literature. The author also discusses what is known and theorized about the pathogenesis of GIVD, and he reviews its diagnosis, treatment, and prevention.


Distinct contributions of beta 4GalNAcTA and beta 4GalNAcTB to Drosophila glycosphingolipid biosynthesis.
Drosophila melanogaster has two beta4-N-acetylgalactosaminyltransferases, beta4GalNAcTA and beta4GalNAcTB, that are able to catalyse the formation of lacdiNAc (GalNAcbeta,4GlcNAc). LacdiNAc is found as a structural element of Drosophila glycosphingolipids (GSLs) suggesting that beta4GalNAcTs contribute to the generation of GSL structures in vivo. Mutations in Egghead and Brainaic, enzymes that generate the beta4GalNAcT trisaccharide acceptor structure GlcNAcbeta,3Manbeta,4GlcbetaCer, are lethal. In contrast, flies doubly mutant for the beta4GalNAcTs are viable and fertile. Here, we describe the structural analysis of the GSLs in beta4GalNAcT mutants and find that in double mutant flies no lacdiNAc structure is generated and the trisaccharide GlcNAcbeta,3Manbeta,4GlcbetaCer accumulates. We also find that phosphoethanolamine transfer to GlcNAc in the trisaccharide does not occur, demonstrating that this step is dependent on prior or simultaneous transfer of GalNAc. By comparing GSL structures generated in the beta4GalNAcT single mutants we show that beta4GalNAcTB is the major enzyme for the overall GSL biosynthesis in adult flies. In beta4GalNAcTA mutants, composition of GSL structures is indistinguishable from wild-type animals. However, in beta4GalNAcTB mutants precursor structures are accumulating in different steps of GSL biosynthesis, without the complete loss of lacdiNAc, indicating that beta4GalNAcTA plays a minor role in generating GSL structures. Together our results demonstrate that both beta4GalNAcTs are able to generate lacdiNAc structures in Drosophila GSL, although with different contributions in vivo, and that the trisaccharide GlcNAcbeta,3Manbeta,4GlcbetaCer is sufficient to avoid the major phenotypic consequences associated with the GSL biosynthetic defects in Brainiac or Egghead.


Evaluation of Resistance Resources and Analysis of Resistance Mechanism of Maize to Stalk Rot Caused by Fusarium graminearum.
Maize stalk rot is one of the most destructive and widely distributed diseases in maize plants worldwide. Research on the performance and resistance mechanism of maize against stem rot is constantly improving. Here, among 120 inbred maize lines infected by Fusarium graminearum using the injection method, 4 lines (3.33%) of them were highly resistant to maize stalk rot, 28 lines (23.33%) were resistant, 57 lines (47.50%) were susceptible, and 31 lines (25.84%) were highly susceptible. The inbred lines 18N10118 and 18N10370 were the most resistant and susceptible with disease indices of 7.5 and 75.6, respectively. Treatment of resistant and susceptible maize inbred seedlings with F. graminearum showed that root hair growth of the susceptible inbred lines was significantly inhibited, and a large number of hyphae attached and adsorbed multiple conidia near the root system. However, the resistant inbred lines were delayed and inconspicuous, with only a few hyphae and spores appearing near the root system. Compared with susceptible inbred lines, resistant maize inbred line seedlings treated with F. graminearum exhibited elevated activities of catalase, phenylalanine ammonia-lyase, polyphenoloxidase, and superoxide dismutase. The authors identified 153 genes related to disease resistance by transcriptome analysis. The mitogen-activated protein kinase (MAPK) signaling pathway and peroxisome pathway mainly regulated the resistance mechanism of maize inbred lines to F. graminearum infection. These two pathways might play an important role in the disease resistance mechanism, and the function of genes in the two pathways must be further studied, which might provide a theoretical basis for further understanding the molecular resistance mechanism of stalk rot and resistance gene mining.


Reaction dynamics in astrochemistry: low-temperature pathways to polycyclic aromatic hydrocarbons in the interstellar medium.
Bimolecular reactions of phenyl-type radicals with the C4 and C5 hydrocarbons vinylacetylene and (methyl-substituted) 1,3-butadiene have been found to synthesize polycyclic aromatic hydrocarbons (PAHs) with naphthalene and 1,4-dihydronaphthalene cores in exoergic and entrance barrierless reactions under single-collision conditions. The reaction mechanism involves the initial formation of a van der Waals complex and addition of a phenyl-type radical to the C1 position of a vinyl-type group through a submerged barrier. Investigations suggest that in the hydrocarbon reactant, the vinyl-type group must be in conjugation with a -C≡CH or -HC=CH2 group to form a resonantly stabilized free radical intermediate, which eventually isomerizes to a cyclic intermediate followed by hydrogen loss and aromatization (PAH formation). The vinylacetylene-mediated formation of PAHs might be expanded to more complex PAHs, such as anthracene and phenanthrene, in cold molecular clouds via barrierless reactions involving phenyl-type radicals, such as naphthyl, which cannot be accounted for by the classical hydrogen abstraction-acetylene addition mechanism.


Main pulmonary artery dilatation in patients with anthracofibrosis.
This study assessed main pulmonary artery diameter of patients with anthracofibrosis. Patients with anthracofibrosis and CT scans were evaluated after exclusion of patients with co-existing disease. We measured the diameter of the main pulmonary artery (PAD) and ascending aorta (AD) and calculated the pulmonary artery to aorta ratio (APR). The upper reference limit for comparison of PAD was 29 mm. Cut-off values for PAD and APR indicating pulmonary hypertension were 33 mm and 1. We correlated the CT parameters with echocardiographic results. Total 51 patients were included in the analysis. The mean PAD, AD, and APR were 33 mm, 38 mm, and 0.87 respectively. The PAD was larger than the upper reference limit, 29 mm (P<0.001). The PAD was >33 mm in 30 (65%) and the APR was >1 in 9 patients (18%). Of 21 patients with echocardiography, 11 (52%) were found to have pulmonary hypertension. There was no statistical difference in the diagnosis of pulmonary hypertension between echocardiography and CT (P=1.000). In conclusion, main pulmonary artery is dilated in patients with anthracofibrosis more than in the healthy population.


Surface sensitivity in scanning transmission x-ray microspectroscopy using secondary electron detection.
The successful integration of electron detection into an existing scanning transmission x-ray microspectroscope (STXM) at the Swiss Light Source is demonstrated. In conventional x-ray detection using a photomultiplier, STXM offers mainly bulk sensitivity combined with high lateral resolution. However, by implementation of a channeltron electron multiplier, the surface sensitivity can be established by the detection of secondary electrons emitted from the sample upon resonant excitation. We describe the experimental setup and discuss several relevant aspects, in particular the schemes to correct for self-absorption in the specimen due to back illumination in case of thicker films.


The isolated lateral retinacular release in the treatment of patellofemoral disorders.
Isolated lateral retinacular release was performed on 102 knees in 76 patients. Diagnoses included chondromalacia patellae, patellar compression syndrome, and subluxation and dislocation of the patella. Patients reported that their symptoms improved after isolated lateral retinacular release in 95 of 102 knees. At follow-up evaluation (mean, 14.5 months after surgery), independent observers found no recurrence of dislocation in the 23 knees having had frank dislocations before surgery. In 71% of the knees with limitation of activity before surgery, unlimited activity was tolerated after isolated lateral retinacular release. Quadriceps exercise tolerance improved from 51% before surgery to 100% after surgery. This improvement in exercise tolerance can provide a significant length of time in which quadriceps rehabilitation can be conducted. Hypothetically, the effect of that lateral retinacular release is a decrease in the work load of an overpowered or weakened vastus medialis obliquus muscle, the major provider of dynamic stability required by the patellofemoral joint.


Dietary influence on the insulin function in the epididymal fat cell of the Wistar rat. II. Effect of type of carbohydrate.
Newly weaned male specific pathogen-free Wistar rats were fed semipurified diets containing sunflowerseed oil or palm oil and various types of carbohydrates, i.e. sucrose, maize starch or potato starch for at least 3-4 weeks. Fat cells were isolated from the epididymal fat pads to study the sensitivity to insulin. The response to insulin of the cells was always higher for sunflowerseed oil than for palm oil. Diets containing polysaccharides were found to induce a higher response as compared to sucrose-containing diets. The changes in insulin response due to the type of carbohydrate were not accompanied by changes in insulin binding to the cells, or in the fatty acid composition of the membrane phospholipids. The fatty acid compositions of the triacylglycerol fractions from the epididymal fat pads reflected very well those of the dietary fats. In addition, the type of dietary carbohydrate had also some effect on this composition. The fecal fatty acid content was low and very similar after diets containing either sucrose or maize starch and sunflowerseed oil or palm oil, indicating that the difference in insulin function between the two dietary fats cannot be caused by a difference in fat absorption in the digestive tract. These findings, as well as the insulin concentrations in the blood samples after the various diets, suggest that the changes in insulin response due to the type of dietary carbohydrate are caused by postreceptor effects.


T-screen to quantify functional potentiating, antagonistic and thyroid hormone-like activities of poly halogenated aromatic hydrocarbons (PHAHs).
The present study investigates chemical thyroid hormone disruption at the level of thyroid hormone receptor (TR) functioning. To this end the (ant)agonistic action of a series of xenobiotics was tested in the newly developed T-screen. This assay makes use of a GH3 rat pituitary cell line, that specifically proliferates when exposed to 3,3',5-triiodo-L-thyronine (T3). The growth stimulatory effect is mediated via T3-receptors. (Ant)agonistic and potentiating action of compounds was studied in absence and presence of T3 at its EC50 level (0.25 nM). The compounds tested included the specific TR-antagonist amiodarone, as well as a series of brominated diphenyl ethers (BDEs), including specifically synthesized BDEs with a structural resemblance to 3,5-diiodo-L-thyronine (T2), T3 and T4 (3,3',5,5'-tetraiodo-L-thyronine). The results obtained reveal that only BDE206 and amiodarone are specific antagonists. Interestingly some compounds which did not respond in the T-screen in absence of T3, potentiated effects when tested in combination with T3. This points at possibilities for disruption at the TR in vivo, where exposure generally occurs in presence of T3. Altogether the results of the present study show that the newly developed T-screen can be used as a valuable tool for identification and quantification of compounds active in disturbing thyroid hormone homeostasis at the level of TR-functioning.


Stereoscopic Image Generation from Light Field with Disparity Scaling and Super-Resolution.
In this paper, we propose a novel method to generate stereoscopic images from light-field images with the intended depth range and simultaneously perform image super-resolution. Subject to the small baseline of neighboring subaperture views and low spatial resolution of light-field images captured using compact commercial light-field cameras, the disparity range of any two subaperture views is usually very small. We propose a method to control the disparity range of the target stereoscopic images with linear or nonlinear disparity scaling and properly resolve the disocclusion problem with the aid of a smooth energy term previously used for texture synthesis. The left and right views of the target stereoscopic image are simultaneously generated by a unified optimization framework, which preserves content coherence between the left and right views by a coherence energy term. The disparity range of the target stereoscopic image can be larger than that of the input light field image. This benefits many light field image-based applications, e.g., displaying light field images on various stereo display devices and generating stereoscopic panoramic images from a light field image montage. An extensive experimental evaluation demonstrates the effectiveness of our method.


Variable response to inhaled nitric oxide in postoperative patients of mitral stenosis with pulmonary hypertension.
This study was carried out to determine the vasodilator response of inhaled nitric oxide in patients with pulmonary hypertension (PH) after valve replacement surgery for mitral valve disease. This Quesi experimental study was carried out at the intensive care unit of Armed Forces Institute of Cardiology (AFIC) in collaboration with Department of Physiology, Army Medical College, Rawalpindi from March 2004 to February 2006. Thirty patients with systolic Pulmonary Artery Pressure (PAP) > 50 mmHg on pre-operative echocardiography were inducted. Swan Ganz catheter was inserted to record baseline pulmonary artery pressure and pulmonary capillary wedge pressure (PCWP), while cardiac output (CO) was recorded through lithium dilution method. Pulmonary Vascular Resistance (PVR) was calculated with the help of a formula. Inhaled nitric oxide (iNO) was administered after the surgery and the same parameters were recorded again after one hour. The majority of patients were females (73%), while males were only 27%. Out of 30, 21 had isolated mitral stenosis and 9 had mixed mitral and aortic valve disease. 22 patients responded significantly to iNO therapy with > or = 40.0% reduction in their baseline PVR while 8 patients showed insignificant improvement in their PVR (663 +/- 233 dynes.sec.cm(-5) to 605 +/- 222 dynes.sec.cm(-5)). Significant improvement in pulmonary vascular resistance in the responders and maintenance of high pressures despite iNO therapy in non-responders indicate that apart from some abnormality in nitric oxide pathway, some other factors may be a contributing in the causation of PH secondary to mitral stenosis in adults, which warrant further studies.


The neurology of acutely failing respiratory mechanics.
Forces involved in breathing-which effectively pull in air-are the diaphragmatic, intercostal, spine, and neck muscles. Equally important is the bulbar musculature maintaining the architecture of a patent airway conduit and abdominal wall and internal intercostal muscles providing cough. Acute injury along a neural trajectory from brainstem to muscle will impair the coordinated interaction between these muscle groups. Acutely failing respiratory mechanics can be caused by central and peripheral lesions. In central lesions, the key lesion is in the nucleus ambiguus innervating the dilator muscles of the soft palate, pharynx, and larynx, but abnormal respiratory mechanics rarely coincide with abnormalities of the respiratory pattern generator. In peripheral lesions, diaphragmatic weakness is a main element, but in many neuromuscular disorders mechanical upper airway obstruction from oropharyngeal weakness contributes equally to an increased respiratory load. The neurology of breathing involves changes in respiratory drive, rhythm, mechanics, and dynamics. This review focuses on the fundamentals of abnormal respiratory mechanics in acute neurologic conditions, bedside judgment, interpretation of additional laboratory tests, and initial stabilization, with practical solutions provided. Many of these respiratory signs are relevant to neurologists, who in acute situations may see these patients first. Ann Neurol 2017;81:485-494.


Travelers' diarrhea: Risk reduction and management.
Travelers' diarrhea is a common complaint for patients traveling abroad. Onset of illness, symptoms experienced, and the duration of symptoms are greatly impacted by the causative agent. This article explores the causes, prevention recommendations, and treatment methodologies recommended for this common condition.


Differential expression of CYB5A in Chinese and European pig breeds due to genetic variations in the promoter region.
Cytochrome b5 (CYB5A) is an important electron transfer protein with homologues in a number of different organisms. In pigs, CYB5A is related to boar taint because of its role in androstenone biosynthesis. To determine the variety of CYB5A expression in pig breeds, genetic variations in the porcine CYB5A promoter region in both Chinese and European pig breeds were examined. Three single nucleotide polymorphisms (NC_010443.4:g.165901487delG, g.165901767T>C and g.165902078C>T) were identified in the porcine CYB5A promoter region. These SNPs occurred in different frequencies in Chinese and European pigs. Chinese pigs were primarily haplotype B (denoted as delG-C-T: the position of nt 165901487 of the CYB5 gene is a G deletion, nt 165901767 is C and nt 165902078 is T), except for Licha black pigs, which were primarily haplotype A (denoted as G-T-C: nt 165901487 is G, nt 165901767 is T and nt 165902078 is C), similar to European pigs. Quantitative PCR data from liver tissues demonstrated that haplotype B individuals had higher CYB5A expression than did those with haplotype A. This was confirmed by in vitro cell transfection assays, in which haplotype B individuals had higher reporter activity than did those with haplotype A. In silico analysis predicted that Myc-associated zinc-finger protein (MAZ) is a potential transcription factor at position 165901767. Electrophoretic mobility shift assays showed this polymorphism affects the stable binding of transcription factors to the CYB5A promoter, which in turn affects the expression levels of this gene. Therefore, this variation of the porcine CYB5A promoter region may explain the differences in androstenone accumulation between Chinese and European pig breeds and may also prove useful as a genetic marker to distinguish the origin of different pig breeds.


[The principle of instantaneous action in photosynthesis].
The principle of instant action for photosynthesis is grounded. According to this principle, all primary photophysical events of energy delivery from light harvesting Chl molecules to reaction centres proceed at time intervals not exceeding critical value approximating 10(-10) seconds. This provides: a) high quantum yield (more then 90%) of primary photosynthesis: b) Chl protection from irreversible photodestruction. Original experimental data obtained by V.I. Godik and the author support the above principle at least for purple bacteria, green bacteria and photosystem I of plants.


Six days in Charity Hospital: two doctors' ordeal in Hurricane Katrina.
Hurricane Katrina devastated the city of New Orleans as well as a large section of the Gulf Coastal region of the United States. Herein, we present a first-hand view of physicians who were actually running the hospital of a major medical center during this natural disaster. This event demonstrates the vulnerability of basic human services, including health care even in industrialized, wealthy countries.


[ALOPECIA AREATA].
Alopecia areata (AA) is an organ specific autoimmune disease. Similar to other autoimmune diseases, its pathogenesis is believed to be an interaction of genetic, environmental and immune factors. Studies have shown that autoreactive lymphocytes affect anagen hair follicles leading to subsequent shedding of hairs and alopecia. Clinically, the disease is characterized by sudden nonscarring hair loss that usually involves the scalp, but may also affect the face and other body areas, and indeed the entire body hair. AA may appear for the first time at any age, affecting both children and adults, but it occurs primarily at a young age with a peak incidence in the second and third decade of life. The disease causes pronounced social and psychological impact. The main therapeutic approaches include immunosuppression through anti-inflammatory agents and immunomodulation based on skin sensitization.


Antibody selection influences the detection of AR-V7 in primary prostate cancer.
The androgen receptor (AR) splice variant V7 (AR-V7) is an emerging marker to aid clinical decision-making in patients with castration-resistant prostate cancer (CRPC). A number of studies have shown that a subset of patients also express AR-V7 in the primary tumor. These findings have recently been challenged by a study showing that AR-V7 becomes only detectable in CRPC but is virtually absent in castration-naïve prostate cancer. Herein, we directly compare the two relevant antibodies used for the immunodetection of AR-V7 in the conflicting studies (clones AG10008 and RM7) in a predominantly high-risk prostate cancer patient cohort with primary tumor specimens assembled in a tissue microarray (TMA). The overall rate of AR-V7 positive TMA cores was comparable (AG10008, 24.9%; RM7, 21%). However, the percentage agreement of identical staining intensities of positive cores was only 7%. In contrast, the percentage agreement of negative cores was 62.8%. In approximately 30% of the cores, the antibodies produced discordant staining intensities. Only one of the two antibody stainings (AG10008) conveyed prognostic information and was associated with a shorter progression-free patient survival. Our study underscores that nuclear AR-V7 expression can be detected in primary prostate cancer prior to long-term androgen deprivation and castration resistance. There are staining differences between the two antibodies in tumor tissue, for which we currently have no explanation. Clearly, improvements in the detection of functional AR-V7 in prostate cancer are urgently needed.


Impaired systolic blood pressure recovery directly after standing predicts mortality in older falls clinic patients.
Normally, standing up causes a blood pressure (BP) drop within 15 seconds, followed by recovery to baseline driven by BP control mechanisms. The prognostic value of this initial BP drop, but also of the recovery hereafter, is unknown. The aim of this study was to examine the prognostic value of these BP characteristics in response to standing. In a retrospective cohort study of 238 consecutive patients visiting our falls outpatient clinic, we examined the relation between all-cause mortality and BP decline and recovery directly after active standing up with Cox proportional hazards analyses. Of 238 patients (mean age 78.4 ± 7.8 years), during a median follow-up of 21.0 months, 36 (15%) patients died. Neither absolute nor relative (%) initial BP drop after standing predicted mortality. In contrast, the magnitude of BP recovery 40-60 seconds after standing was associated with mortality, even after adjustment for age, comorbidity, and other baseline characteristics. When systolic BP had recovered to less than 80% of prestanding baseline after 60 seconds of standing, this was a powerful independent predictor of mortality (hazard ratio: 3.00; 95% confidence interval 1.17-7.68). Failure to recover from BP decline in the first minute after active standing up is associated with excess mortality in falls clinic patients. A recovery of systolic BP to less than 80% of baseline after 60 seconds may be used as an easily available cardiovascular marker for increased mortality risk in older falls clinic patients.


High-programmed death-1 levels on hepatitis C virus-specific T cells during acute infection are associated with viral persistence and require preservation of cognate antigen during chronic infection.
Hepatitis C virus (HCV) is an important human pathogen that represents a model for chronic infection given that the majority of infected individuals fail to clear the infection despite generation of virus-specific T cell responses during the period of acute infection. Although viral sequence evolution at targeted MHC class I-restricted epitopes represents one mechanism for immune escape in HCV, many targeted epitopes remain intact under circumstances of viral persistence. To explore alternative mechanisms of HCV immune evasion, we analyzed patterns of expression of a major inhibitory receptor on T cells, programmed death-1 (PD-1), from the time of initial infection and correlated these with HCV RNA levels, outcome of infection, and sequence escape within the targeted epitope. We show that the level of PD-1 expression in early HCV infection is significantly higher on HCV-specific T cells from subjects who progress to chronic HCV infection than from those who clear infection. This correlation is independent of HCV RNA levels, compatible with the notion that high PD-1 expression on HCV-specific CD8 T cells during acute infection inhibits viral clearance. Viral escape during persistent infection is associated with reduction in PD-1 levels on the surface of HCV-specific T cells, supporting the necessity of ongoing antigenic stimulation of T cells for maintenance of PD-1 expression. These results support the idea that PD-1 expression on T cells specific for nonescaped epitopes contributes to viral persistence and suggest that PD-1 blockade may alter the outcome of HCV infection.


The painful hip.
Diagnosis of the cause of a painful hip joint can be difficult. Some conditions require urgent diagnosis and management but in many instances careful observation over a period of time constitutes good management of the patient.


Efficiency and Safety of CRAC Inhibitors in Human Rheumatoid Arthritis Xenograft Models.
Store-operated Ca2+ release-activated Ca2+ (CRAC) channels are involved in the pathogenesis of rheumatoid arthritis (RA) and have been studied as therapeutic targets in the management of RA. We investigated the efficacy and safety of CRAC inhibitors, including a neutralizing Ab (hCRACM1-IgG) and YM-58483, in the treatment of RA. Patient-derived T cell and B cell activity was suppressed by hCRACM1-IgG as well as YM-58483. Systemically constant, s.c. infused CRAC inhibitors showed anti-inflammatory activity in a human-NOD/SCID xenograft RA model as well as protective effects against the destruction of cartilage and bone. hCRACM1-IgG appeared to be safe for systemic application, whereas YM-58483 showed hepatic and renal toxicity in xenograft mice. Treatment with both CRAC inhibitors also caused hyperglycemia in xenograft mice. These results indicate the potential of hCRACM1-IgG and YM-58483 as anti-immunological agents for the treatment of RA. However, some safety issues should be addressed and application methods should be optimized prior to their clinical use.


Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse.
Cathelicidins are the precursors of potent antimicrobial peptides that have been identified in several mammalian species. Prior work has suggested that members of this gene family can participate in host defense through their antimicrobial effects and activate mesenchymal cells during wound repair. To permit further study of these proteins a reverse transcriptase-polymerase chain reaction approach was used to identify potential mouse homologs. A full-length 562-base pair cDNA clone was obtained encoding an NH2-terminal prepro domain homologous to other cathelicidins and a unique COOH-terminal peptide. This gene, named Cramp for cathelin-related antimicrobial peptide, was mapped to chromosome 9 at a region of conserved synteny to which genes for cathelicidins have been mapped in pig and man. Northern blot analysis detected a 1-kilobase transcript that was expressed in adult bone marrow and during embryogenesis as early as E12, the earliest stage of blood development. Reverse transcriptase-polymerase chain reaction also detected CRAMP expression in adult testis, spleen, stomach, and intestine but not in brain, liver, heart, or skeletal muscle. To evaluate further the expression and function of CRAMP, a peptide corresponding to the predicted COOH-terminal region was synthesized. CD spectral analysis showed that CRAMP will form an amphipathic alpha-helix similar to other antimicrobial peptides. Functional studies showed CRAMP to be a potent antibiotic against Gram-negative bacteria by inhibiting growth of a variety of bacterial strains (minimum inhibitory concentrations 0.5-8.0 microM) and by permeabilizing the inner membrane of Escherichia coli directly at 1 microM. Antiserum against CRAMP revealed abundant expression in myeloid precursors and neutrophils. Thus, CRAMP represents the first antibiotic peptide found in cells of myeloid lineage in the mouse. These data suggest that inflammatory cells in the mouse can use a nonoxidative mechanism for microbial killing and permit use of the mouse to study the role such peptides play in host defense and wound repair.


Bridgehead carbocations via carbene fragmentation: erasing a 10(10) kinetic preference.
1-Norbornyloxychlorocarbene (1-NorOCCl), 1-bicyclo[2.2.2]octyloxychlorocarbene (1-BcoOCCl), and 1-adamantyloxychlorocarbene (1-AdOCCl) were generated in dichloroethane (DCE) by photolysis of the appropriate diazirines. The exclusive product in each case was the bridgehead alkyl chloride formed by fragmentation of the carbene to [R(+) OC Cl(-)] ion pairs, loss of CO, and cation-anion collapse. In mixtures of methanol and DCE, each carbene gave three products: RCl, ROH, and ROMe. RCl and ROMe resulted from competition between ion pair collapse and methanol capture of the cation. ROH resulted from methanol capture of the carbene (before fragmentation), followed by eventual methanolysis and hydrolysis of ROCH(Cl)OMe. The ratios of carbene capture to carbene fragmentation fell in the order 1-NorOCCl > BcoOCCl > 1-AdOCCl; 1-Nor(+) was the least stable cation and the slowest to form by fragmentation, so that this carbene was the most readily captured. This trend was accentuated in methanol-pentane mixtures, where ionic fragmentation was further slowed in the less polar solvent. Laser flash photolysis with either UV or time-resolved infrared (TRIR) monitoring permitted the determination of the absolute rate constants for fragmentations of the carbenes in DCE at 25 degrees C. The rate constants (s(-1)) were: 1-NorOCCl (3.3 x 10(4)), 1-BcoOCCl (1.5 x 10(5)), and 1-AdOCCl (5.9 x 10(5)). The rate constants decreased in the order of increasing strain in the resulting bridgehead carbocation, but the range of rate constants was compressed to a factor of only approximately 18. This constrasts with the factor of 10(10) by which the acetolysis of 1-AdOTs at 70 degrees C exceeded that of 1-NorOTs. The fragmentation of 1-NorOCCl to the ion pair was 3 x 10(15) times faster than the acetolysis of 1-NorOTs. The activation energies were measured as 9.0 kcal/mol (log A = 11.2 s(-1)) for the fragmentation of 1-NorOCCl and 4.4 kcal/mol (log A = 8.44 s(-1)) for that of 1-BcoOCCl both in DCE. B3LYP/6-31G computed activation energies in simulated DCE were 14.6 and 2.7 kcal/mol, respectively.


Vaccination and otitis media.
Acute otitis media (AOM) caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis may induce specific systemic and/or local immune responses, which may protect from otitis media caused by the same bacteria. However, earlier clinical trials with pneumococcal capsular polysaccharide vaccines have not been successful in preventing AOM. Recently developed pneumococcal polysaccharide-protein conjugates proved immunogenic even in infants, and a heptavalent pneumococcal CRM 197 conjugate vaccine gave a 57% reduction in the number of pneumococcal AOM episodes caused by the vaccine serotypes in infants in Finland. H. influenzae causing AOM is noncapsulated, and like M. catarrhalis, calls for another kind of vaccine development. Suitable vaccine candidates are not yet available but are under development and being tested for immunogenicity and safety. In some trials influenza vaccines have shown protection from AOM during respective viral epidemics. Passive immunoprophylaxis might be an important alternative for immunocompromised children, although this approach has not been successful so far. Mucosal immunization and the advent of DNA and gene technology will open new interesting prospects in the future.


Taxonomic and ecological relevance of the chlorophyll a fluorescence signature of tree species in mixed European forests.
The variability of chlorophyll a fluorescence (ChlF) parameters of forest tree species was investigated in 209 stands belonging to six European forests, from Mediterranean to boreal regions. The modifying role of environmental factors, forest structure and tree diversity (species richness and composition) on ChlF signature was analysed. At the European level, conifers showed higher potential performance than broadleaf species. Forests in central Europe performed better than those in Mediterranean and boreal regions. At the site level, homogeneous clusters of tree species were identified by means of a principal component analysis (PCA) of ChlF parameters. The discrimination of the clusters of species was influenced by their taxonomic position and ecological characteristics. The species richness influenced the tree ChlF properties in different ways depending on tree species and site. Tree species and site also affected the relationships between ChlF parameters and other plant functional traits (specific leaf area, leaf nitrogen content, light-saturated photosynthesis, wood density, leaf carbon isotope composition). The assessment of the photosynthetic properties of tree species, by means of ChlF parameters, in relation to their functional traits, is a relevant issue for studies in forest ecology. The connections of data from field surveys with remotely assessed parameters must be carefully explored.


Recent Advances of Hepatitis B Detection towards Paper-Based Analytical Devices.
Hepatitis B virus (HBV) still remains a major global public health problem. One-half to one-third of the total HBV infected people died due to late detection of HBV. Serological antigen and viral HBV detections can help in the diagnosis, referral, and treatment of HBV. Available methods for HBV detection mostly used bulky instruments. Miniaturization of devices for HBV detection has been started by narrowing down the size of the devices. Several methods have also been proposed to increase the selectivity and sensitivity of the miniaturized methods, such as sandwich recognition of the biomarkers and the use of nano- to micro-sized materials. This review presents recent HBV detections in the last two decades from laboratory-based instruments towards microfluidic paper-based analytical devices (µPADs) for point-of-care testing (POCT) purposes. Early and routine analysis to detect HBV as early as possible could be achieved by POCT, especially for areas with limited access to a central laboratory and/or medical facilities.


Purification and properties of a novel recombinant human hybrid interferon, delta-4 alpha 2/alpha 1.
The human interferon (huIFN) delta-4 alpha 2(5-62)/alpha 1(64-166) is a genetically engineered hybrid that consists of residues 5-62 of huIFN alpha 2 and residues 64-166 of huIFN alpha 1. This variant contains four cysteine residues at positions 29, 86, 99 and 139, but does not contain the cysteine at position 1 that is characteristic of naturally occurring huIFN alpha subtypes. This novel recombinant hybrid was purified from Escherichia coli to greater than 95% homogeneity. The purification was based on ethanol extraction of a trichloroacetic acid precipitate and Matrex Gel Blue A chromatography followed by either a selective precipitation or DEAE-Sepharose chromatography. The purified protein that was treated with 2-mercaptoethanol exhibited two closely migrating bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with apparent molecular weight values of 17,800 and 17,100, both of which exhibited antiviral activity. Electrophoresis performed without prior reduction with 2-mercaptoethanol indicated only a minor extent of intermolecular disulfide bonding. The purified protein exhibited a high specific antiviral activity of 7 x 10(7) units/mg when assayed on human fibroblast cells and, in distinction to the parental huIFN alpha 2, it also demonstrated antiviral activity on human fibroblast cells and, in distinction to the parental huIFN alpha 2, it also demonstrated antiviral activity on murine L929 cells. The level of antiproliferative activity of huIFN delta-4 alpha 2(5-62)/alpha 1(64-166) on various cell lines of different histological origin appeared to be more comparable to that of huIFN alpha 1 than huIFN alpha 2. The data suggest that huIFN delta-4 alpha 2(5-62)/alpha 1(64-166) hybrid may be a useful tool for understanding huIFN structure-function relations.


Criteria for selecting PEGylation sites on proteins for higher thermodynamic and proteolytic stability.
PEGylation of protein side chains has been used for more than 30 years to enhance the pharmacokinetic properties of protein drugs. However, there are no structure- or sequence-based guidelines for selecting sites that provide optimal PEG-based pharmacokinetic enhancement with minimal losses to biological activity. We hypothesize that globally optimal PEGylation sites are characterized by the ability of the PEG oligomer to increase protein conformational stability; however, the current understanding of how PEG influences the conformational stability of proteins is incomplete. Here we use the WW domain of the human protein Pin 1 (WW) as a model system to probe the impact of PEG on protein conformational stability. Using a combination of experimental and theoretical approaches, we develop a structure-based method for predicting which sites within WW are most likely to experience PEG-based stabilization, and we show that this method correctly predicts the location of a stabilizing PEGylation site within the chicken Src SH3 domain. PEG-based stabilization in WW is associated with enhanced resistance to proteolysis, is entropic in origin, and likely involves disruption by PEG of the network of hydrogen-bound solvent molecules that surround the protein. Our results highlight the possibility of using modern site-specific PEGylation techniques to install PEG oligomers at predetermined locations where PEG will provide optimal increases in conformational and proteolytic stability.


Irony as a Test of the Presupposition-Denial Account: An ERP Study.
According to the Presupposition-Denial Account, complement set reference arises when focus is on the shortfall between the amount conveyed by a natural language quantifier and a larger, expected amount. Negative quantifiers imply a shortfall, through the denial of a presupposition, whereas positive quantifiers do not. An exception may be provided by irony. One function of irony is to highlight, through indirect negation, the shortfall between what is expected/desired, and what is observed. Thus, a positive quantifier used ironically should also lead to a shortfall and license complement set reference. Using ERPs, we examined whether reference to the complement set is more felicitous following a positive quantifier used ironically than one used non-ironically. ERPs during reading showed a smaller N400 for complement set reference following an ironic compared to a non-ironic context. The shortfall generated thorough irony is sufficient to allow focus on the complement set, supporting the Presupposition-Denial Account.


Spectrum of spontaneous mutations in the cyclic AMP receptor protein gene on chromosomal DNA of Escherichia coli.
We determined 46 spontaneous mutations occurring in the cyclic AMP receptor protein gene (crp) on the chromosomal DNA of Escherichia coli by the use of PCR cloning. Of 24 base substitutions, 17 were transversions and 7 transitions including all types of base substitutions. The frequency of the changes of A:T base pairs was similar to that of G:C pairs, suggesting that A:T pair is also a target for base substitution. Frameshifts including seven-1 and four +1 frameshifts occurred at the sites of a run of identical bases. Deletions extending 18 and 172 bases occurred at the sites where the deleted sequences were flanked by short repeated sequences at the junction. The insertions of IS2 element or its inverted sequence were detected in two and six mutations, respectively. The assay system of the mutation used here is available for the determination of the mutational spectrum of base substitutions.


Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers FGF22 and FGF7.
Specific formation of excitatory and inhibitory synapses is crucial for proper functioning of the brain. Fibroblast growth factor 22 (FGF22) and FGF7 are postsynaptic-cell-derived presynaptic organizers necessary for excitatory and inhibitory presynaptic differentiation, respectively, in the hippocampus. For the establishment of specific synaptic networks, these FGFs must localize to appropriate synaptic locations - FGF22 to excitatory and FGF7 to inhibitory postsynaptic sites. Here, we show that distinct motor and adaptor proteins contribute to intracellular microtubule transport of FGF22 and FGF7. Excitatory synaptic targeting of FGF22 requires the motor proteins KIF3A and KIF17 and the adaptor protein SAP102 (also known as DLG3). By contrast, inhibitory synaptic targeting of FGF7 requires the motor KIF5 and the adaptor gephyrin. Time-lapse imaging shows that FGF22 moves with SAP102, whereas FGF7 moves with gephyrin. These results reveal the basis of selective targeting of the excitatory and inhibitory presynaptic organizers that supports their different synaptogenic functions. Finally, we found that knockdown of SAP102 or PSD95 (also known as DLG4), which impairs the differentiation of excitatory synapses, alters FGF7 localization, suggesting that signals from excitatory synapses might regulate inhibitory synapse formation by controlling the distribution of the inhibitory presynaptic organizer.


Risk and predictors of severity and mortality in patients with type 2 diabetes and COVID-19 in Dubai.
Globally, patients with diabetes suffer from increased disease severity and mortality due to coronavirus disease 2019 (COVID-19). Old age, high body mass index (BMI), comorbidities, and complications of diabetes are recognized as major risk factors for infection severity and mortality. To investigate the risk and predictors of higher severity and mortality among in-hospital patients with COVID-19 and type 2 diabetes (T2D) during the first wave of the pandemic in Dubai (March-September 2020). In this cross-sectional nested case-control study, a total of 1083 patients with COVID-19 were recruited. This study included 890 men and 193 women. Of these, 427 had T2D and 656 were non-diabetic. The clinical, radiographic, and laboratory data of the patients with and without T2D were compared. Independent predictors of mortality in COVID-19 non-survivors were identified in patients with and without T2D. T2D patients with COVID-19 were older and had higher BMI than those without T2D. They had higher rates of comorbidities such as hypertension, ischemic heart disease, heart failure, and more life-threatening complications. All laboratory parameters of disease severity were significantly higher than in those without T2D. Therefore, these patients had a longer hospital stay and a significantly higher mortality rate. They died from COVID-19 at a rate three times higher than patients without. Most laboratory and radiographic severity indices in non-survivors were high in patients with and without T2D. In the univariate analysis of the predictors of mortality among all COVID-19 non-survivors, significant associations were identified with old age, increased white blood cell count, lym-phopenia, and elevated serum troponin levels. In multivariate analysis, only lymphopenia was identified as an independent predictor of mortality among T2D non-survivors. Patients with COVID-19 and T2D were older with higher BMI, more comorbidities, higher disease severity indices, more severe proinflammatory state with cardiac involvement, and died from COVID-19 at three times the rate of patients without T2D. The identified mortality predictors will help healthcare workers prioritize the management of patients with COVID-19.


Robust Zinc Anode Enabled by Sulfonate-Rich MOF-Modified Separator.
Aqueous zinc ion batteries (ZIBs) hold great promise for large-scale energy storage; however, severe zinc dendritic growth and side reactions on the anode dramatically impede their commercial application. Herein, a Zr-based MOF (UiO-66) functionalized with a high density of sulfonic acid (─SO3 H) groups is used to modify the glass fiber (GF) separator of ZIBs, providing a unique solution for stabilizing Zn anode. Benefiting from the strong interaction between zincophilic -SO3 H and Zn2+ , this sulfonate-rich UiO-66 modified GF (GF@UiO-S2) separator not only guarantees the homogeneous distribution of ion flux, but also accelerates the ion migration kinetics. Hence, the GF@UiO-S2 separator promotes uniform Zn plating/stripping on the Zn anode and facilitates the desolvation of hydrated Zn2+ ions at the interface, which helps guide dendrite-free Zn deposition and inhibit undesired side reactions. Accordingly, the Zn||Zn symmetric cell with this separator achieves excellent cycling stability with a long cycle life exceeding 3450 h at 3 mA cm-2 . Besides, the Zn||MnO2 full cell paired with this separator delivers remarkable cyclability with 90% capacity retention after 1200 cycles. This design of metal-organic frameworks functionalized separators provides a new insight for constructing highly robust ZIBs.


Influence of chronic ethanol consumption on extra-pancreatic secretory function in rat.
The usefulness of the typical direct methods involving duodenal intubation, such as the secretin and secretin-cholecystokinin tests, in the diagnosis of exocrine pancreatic dysfunction is widely accepted. However, these diagnostic tests tend to be avoided because of their technical complexity and the burden on patients. Recently, a simple breath test was developed for assessment of exocrine pancreatic function employing 13C-dipeptide [i.e., benzoyl-L-tyrosyl-[1-13C] alanine (Bz-Tyr-Ala)]. Although alcohol abuse causes pancreatic damage in humans, this has been unclear in rats. The aim of the study is to evaluate the effect of ethanol exposure beginning at an early age on extra-pancreatic secretory function in rats. Twelve female rats of the F344 strain aged 12 months were used. Seven rats were fed on a commercial mash food with 16% ethanol solution (Japanese Sake) as drinking-fluid since at 29 days of age (ethanol group). The remaining five rats were fed on a nutrient-matched isocaloric diet with water as drinking-fluid (control group). After 24-hr fasting, rats are orally administrated 1cc of water containing sodium 13C-dipeptide (5 mg/kg) and housed in an animal chamber. The expired air in the chamber is collected in a breath-sampling bag using a tube and aspiration pump. The 13CO2 concentration is measured using an infrared spectrometer at 10-min interval for 120 min and expressed as delta per mil. The breath 13CO2 level increased and peaked at 20 min in both two groups. In general, 13CO2 excretion peaked rapidly and also decreased sooner in ethanol rats than in control rats. The mean value of the maximal 13CO2 excretion is 34.7 per mil in ethanol rats, greater than in control rats (31.4 per mil), but the difference did not reach the statistically significance. Chronic ethanol feeding beginning at an early age does not affect extra-pancreatic secretory function in rats.


Growing pains for new academic/industry relationships.
Five decades of almost unwavering federal support of university research in biomedicine have spawned a biotechnology revolution that holds dramatic promise for the public health and the U.S. economy. To make that promise a reality, the federal government now strongly encourages universities to facilitate the practical application of research results by by participating in academic/industry relationships. These relationships are yielding important health and economic benefits, but the new economic entanglements of U.S. universities also could undermine the public trust that has sustained federal support of biomedical research. Thus, efforts to speed the transfer of technologies through academic/industry relationships may have enormous effects on the government/university partnership that gave birth to those technologies.


Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress-Endoplasmic reticulum stress-Autophagy signaling pathways.
Optic neuropathy is an affection of the optic neurons, which ends with blindness and occurs either primarily due to direct affection of the optic nerve or secondarily as a complication of chronic diseases and/or adverse effects of their therapy. The search for novel therapeutic tools is crucial in addressing the limited therapeutic approaches for optic neuropathy. Therefore, the present study was developed to investigate the possible ameliorative effect of tempol against cisplatin-induced optic neuropathy and its underlying mechanism. Forty-eight adult male albino Wistar rats were divided into four equal groups-control, tempol (TEM), cisplatin (CIS), and tempol and cisplatin combined (TEM+CIS). Optic nerve oxidative stress (MDA, SOD, and GPx), gene expression of endoplasmic reticulum stress (ATF-6, XBP-1, BIP, CHOP, and JNK), autophagy 6 (LC3, Beclin-1, and p62) markers, nerve growth factor-1, immunohistochemical expression of (LC3 and p62), histopathological, and electron microscopic examination were performed. Histopathological and ultrastructure examination validated that cisplatin caused optic neuropathy by inducing oxidative stress, upregulating ER stress markers, and downregulating autophagy markers, and NGF-1 expression. TEM + CIS showed improvement in optic nerve structure and ultrastructure along with oxidative stress, ER stress mRNA, autophagy (immunohistochemical proteins and mRNA) markers, and nerve growth factor mRNA expression. Based on previous findings, tempol represents a valid aid in cisplatin-induced optic neuropathy by implicating new molecular drug targets (ER stress and autophagy) for optic neuropathy therapy.


Rapid Characterization of the Human Breast Milk Lipidome Using a Solid-Phase Microextraction and Liquid Chromatography-Mass Spectrometry-Based Approach.
Human breast milk (HBM) is a biofluid consisting of various biomolecules such as proteins, lipids, carbohydrates, minerals and bioactive substances. Due to its unique and complex composition, HBM provides not only nutritional components required for the growth of the infant, but also additional protection against infections. Global insight into the composition of HBM is crucial to understanding the health benefits infants receive from breastfeeding and could be used to improve the composition of milk formula for babies that cannot be breastfed. To improve global profiling of the HBM lipidome, a new analytical approach based on solid-phase microextraction (SPME) and liquid chromatography-mass spectrometry (LC-MS) was developed. The new extraction method allows for the rapid and simple extraction of a broad range of lipids directly from HBM samples. Moreover, the optimized two-step lipid extraction protocol ensures high lipidome coverage without using toxic solvents such as chloroform. The use of liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) and an automated search of a lipid database allows comprehensive identification of the lipids contained in HBM. The demonstrated analytical approach based on SPME sample preparation and LC-Q-TOF-MS is rapid, free of toxic solvents, and suited for the qualitative analysis of the HBM lipid composition.


Pharmacokinetic comparison of seven 8-methoxypsoralen brands.
The pharmacokinetics of seven 8-MOP brands were evaluated in 7 volunteers using an incomplete bloc design. After a single oral dose the 8-MOP plasma level was followed for 3 hours. The plasma concentration was measured with a gas chromatographic - mass spectrometric method, using an isotopic dilution technique. The different brands could be divided into three groups. Two gave a high maximum concentration, four a medium, and one a low concentration. The large interbrand variation observed in this study can explain the variations in the results of the treatment and the differing numbers of joules required to clear the patients in various PUVA centers.


Ketoacidosis associated with low-carbohydrate diet in a non-diabetic lactating woman: a case report.
Non-diabetic ketoacidosis is a rare condition which can be caused by starvation. Lack of glucose can force the body into ketogenesis causing a metabolic acidosis. As previously reported in the literature, ketoacidosis might, on rare occasions, be caused by a diet with low carbohydrate content. However, to the best of our knowledge this is the first reported case in the literature of ketoacidosis, in a non-diabetic patient, associated with a combination of low carbohydrate, high fat diet and lactation. A healthy non-diabetic, 32-year old white woman started a low carbohydrate, high fat diet when she was breastfeeding her son of 10 months of age. After 10 days she was admitted to our hospital with nausea and vomiting and a serum pH of 7.20 and base excess of -19. Clinical signs and blood samples were compatible with ketoacidosis. She was given fluids intravenously and insulin. No anamnestic or clinical signs of diabetes were found. She recovered quickly and was discharged 3 days later. Ketogenic diets like low carbohydrate, high fat may induce ketoacidosis. Lactation might further aggravate the condition and can perhaps even be the trigger into ketoacidosis. Health services should be aware of the risks associated with ketogenic diets, and be able to recognize this serious condition when it is presented.


Unravelling the diversity of the genus Afronurus Lestage, 1924 (Ephemeroptera, Heptageniidae) in Thailand.
The genus Afronurus in Thailand is investigated using an integrative approach (morphology based, ootaxonomy and molecular data) for species delimitation. A total of four species of Afronurus was identified; A.cervina (Braasch & Soldán, 1984), A.gilliesiana (Braasch, 1990), A.rainulfiana (Braasch, 1990), and A.rubromaculata (You et al., 1981). The subimago of A.gilliesiana is described for the first time based on reared specimens. The egg structure of all four species is also described for the first time. Morphological and molecular data strongly support their species delimitation. The egg chorionic structure of the genus Afronurus, together with other morphological characters, is useful for species identification. A key to mature nymphs of the known species is provided.


1,3,4-Thiadiazole Scaffold: As Anti-Epileptic Agents.
A wide range of biological activities is exhibited by 1,3,4-thiadiazole moiety such as antidiabetic, anticancer, anti-inflammatory, anticonvulsant, antiviral, antihypertensive, and antimicrobial. To date, drugs such as butazolamide, and acetazolamide. Several modifications have been done in the 1,3,4-thiadiazole moiety which showed good potency as anticonvulsant agents which are highly effective and have less toxicity. After in-depth literature survey in this review, we have compiled various derivatives of 1,3,4-thiadiazole scaffold as anticonvulsant agents.


An alternate method of calculating the heat of growth of Escherichia coli K-12 on succinic acid.
The DeltaH(f)(0) unit weight of a complex substance such as a biological macromolecule is almost always obtained by means of combustion analysis. In theory, this can also be done by summing the DeltaH(f)(0) values for the monomers comprising the macromolecule plus the enthalpic energies involved in their polymerization. The enthalpy of formation of one unit-carbon formula weight of dried Escherichia coli K-12 cells was determined by summing the values of the enthalpies of formation of the quantities of monomers in the major classes of macromolecules substances comprising the cellular biomass and the enthalpic energies involved in their polymerizations. To this value was added the enthalpy of formation of the cellular ions in their aqueous standard states, per unit-carbon formula weight of cellular substance and the enthalpy change with respect to the ionization of the protein amino acid side chains. If it is assumed that the cellular fabric is insoluble and that the ions are soluble, the sum of the enthalpies of formation of all the cellular components should closely approximate the enthalpy of formation of one unit-carbon formula weight equivalent of living cells. Using this value, a calculation of the enthalpy change accompanying anabolism shows this latter to be effectively zero, indicating that the heat of growth (anabolism plus catabolism) is equal to that calculated for catabolism alone. This conclusion is in accord with those of several investigators who have used manometry or direct calorimetry.


Thiol-Triggered Release of Intraliposomal Content from Liposomes Made of Extremophile-Inspired Tetraether Lipids.
Liposomal drug-delivery systems have been used for delivery of drugs to targeted tissues while reducing unwanted side effects. DOXIL, for instance, is a liposomal formulation of the anticancer agent doxorubicin (DOX) that has been used to address problems associated with nonspecific toxicity of free DOX. However, while this liposomal formulation allows for a more-stable circulation of doxorubicin in the body compared to free drug, the efficacy for cancer therapy is reduced in comparison with systemic injections of free drug. A robust liposomal system that can be triggered to release DOX in cancer cells could mitigate problems associated with reduced drug efficacy. In this work, we present a serum-stable, cholesterol-integrated tetraether lipid comprising of a cleavable disulfide bond, {GcGT(S-S)PC-CH}, that is designed to respond to the reducing environment of the cell to trigger the release intraliposomal content upon cellular uptake by cancer cells. A cell viability assay revealed that DOX- loaded liposomes composed of pure GcGT(S-S)PC-CH lipids were ∼20 times more toxic than DOXIL, with an IC50 value comparable to that of free DOX. The low inherent membrane-leakage properties of GcGT(S-S)PC-CH liposomes in the presence of serum, combined with an intracellular triggered release of encapsulated cargo, represents a promising approach for developing improved drug-delivery formulations for the treatment of cancer and possibly other diseases.


[Cloning, heterologous expression and purification of a 3-ketosteroid-9alpha-hydroxylase (KSH) from Mycobacterium sp. NwIB-01].
3-ketosteroid-9alpha-hydroxylase (KSH), a key enzyme in the microbial steroid degradation, is highly valuable for the production of some steroid drugs. Degenerate primers were designed by comparing the ksh from Rhodococcus erythropolis SQ1 and its homologous sequences in the reported genome of Mycobacteria. Subsequently, a gene fragment of KSH was cloned from Mycobacterium sp. NwIB-01, a sterol-transforming bacterium isolated from soil in our lab. According to the conservative sequence, the full-length 1188 bp gene encoding ksh (designated as M.S.-ksh) was obtained by chromosome walking, which showed 85% identity with the ksh of M. smegmatis mc(2)155. The heterologous expression of KSH was achieved in Escherichia coli BL21(DE3) using the pET-32a-c(+) vector system. The expressed KSH protein was mostly in soluble form after IPTG induction at 30 degreesC and accounted for more than 30% of total bacterial proteins according to SDS-PAGE electrophoresis. The molecular mass of KSH was about 45 kD, which was exactly the size predicted. After Ni2+ affinity chromatography, the purity of the target protein was more than 90%. Our work will definitely contribute to the industrial production of some steroid drugs by developing KSH genetically engineered bacteria.


tris-Heteroleptic cyclometalated iridium(III) complexes with ambipolar or electron injection/transport features for highly efficient electrophosphorescent devices.
A series of tris-heteroleptic phosphorescent cyclometalated Ir(III) complexes with two different cyclometalating ligands and one ancillary ligand was synthesized. Through manipulation of the electronic features of individual cyclometalating ligands, not only the emission color and electrochemical properties of these Ir(III) complexes can be tuned, but also unique charge carrier injection and transport traits can be conferred to them. Owing to the enhanced electron injection/transport and ambipolar characters associated with these tris-heteroleptic structures, these Ir(III) emitters showed very impressive electroluminescent performance with a maximum external quantum efficiency of 20.20 %, luminance efficiency of 69.41 cd A(-1) and power efficiency of 35.15 Lm W(-1) . These results provide a new outlet to design and synthesize highly efficient electrophosphors for phosphorescent organic light-emitting diodes.


Progressive Macula Vessel Density Loss in Primary Open-Angle Glaucoma: A Longitudinal Study.
To characterize the rate of macula vessel density loss in primary open-angle glaucoma (POAG), glaucoma-suspect, and healthy eyes. Longitudinal, observational cohort from the Diagnostic Innovations in Glaucoma Study. One hundred eyes (32 POAG, 30 glaucoma-suspect, and 38 healthy) followed for at least 1 year with optical coherence tomography angiography (OCT-A) imaging on at least 2 visits were included. Vessel density was calculated in the macula superficial layer. The rate of change was compared across diagnostic groups using a multivariate linear mixed-effects model. Baseline macula vessel density was highest in healthy eyes, followed by glaucoma-suspect and POAG eyes (P < .01). The rate of vessel density loss was significantly different from zero in the POAG, but not in the glaucoma-suspect or healthy eyes. The mean rate of change in macula whole en face vessel density was significantly faster in glaucoma eyes (-2.23%/y) than in glaucoma-suspect (0.87%/y, P = .001) or healthy eyes (0.29%/y, P = .004). Conversely, the rate of change in ganglion cell complex (GCC) thickness was not significantly different from zero in any diagnostic group, and no significant differences in the rate of GCC change among diagnostic groups were found. With a mean follow-up of less than 14 months, eyes with POAG had significantly faster loss of macula vessel density than either glaucoma-suspect or healthy eyes. Serial OCT-A measurements also detected glaucomatous change in macula vessel density in eyes without evidence of change in GCC thickness.


The Cost-Effectiveness of Hyperlipidemia Medication in Low- and Middle-Income Countries: A Review.
Hyperlipidemia is a risk factor for cardiovascular disease - the leading cause of death globally. Increased understanding of the cost-effectiveness of hyperlipidemia treatment in low- and middle-income countries can guide approaches to hyperlipidemia management in resource-limited environments. We conducted a systematic review of the evidence on the cost-effectiveness of hyperlipidemia medication treatment in low- and middle-income countries using studies published between January 2010 and April 2020. We abstracted study details, including study design, treatment setting, intervention type, health metrics, costs standardized to constant 2019 US dollars, and cost-effectiveness measures including average and incremental cost-effectiveness ratios. Comparisons across studies suggested that treatment via polypill is generally more cost-effective than statin-only therapy, and that primary prevention is more cost-effective than secondary prevention. Treating hyperlipidemia at a threshold of 5.7 mmol/l comes at a higher cost per disability-adjusted life-years averted than at a threshold of 6.2 mmol/l. Most pharmacological treatment strategies for hyperlipidemia were found to be cost-effective in most of the examined low- and middle-income countries.


Integrin-linked kinase (ILK) regulates KRAS, IPP complex and Ras suppressor-1 (RSU1) promoting lung adenocarcinoma progression and poor survival.
Integrin-linked kinase (ILK) forms a heterotrimeric protein complex with PINCH and PARVIN (IPP) in Focal Adhesions (FAs) that acts as a signaling platform between the cell and its microenvironment regulating important cancer-related functions. We aimed to elucidate the role of ILK in lung adenocarcinoma (LUADC) focusing on a possible link with KRAS oncogene. We used immunohistochemistry on human tissue samples and KRAS-driven LUADC in mice, analysis of large scale publicly available RNA sequencing data, ILK overexpression and pharmacological inhibition as well as knockdown of KRAS in lung cancer cells. ILK, PINCH1 and PARVB (IPP) proteins are overexpressed in human LUADC and KRAS-driven LUADC in mice representing poor prognostic indicators. Genes implicated in ILK signaling are significantly enriched in KRAS-driven LUADC. Silencing of KRAS, as well as, overexpression and pharmacological inhibition of ILK in lung cancer cells provide evidence of a two-way association between ILK and KRAS. Upregulation of PINCH, PARVB and Ras suppressor-1 (RSU1) expression was demonstrated in ILK overexpressing lung cancer cells in addition to a significant positive correlation between these factors in tissue samples, while KRAS silencing downregulates IPP and RSU1. Pharmacological inhibition of ILK in KRAS mutant lung cancer cells suppresses cell growth, migration, EMT and increases sensitivity to platinum-based chemotherapy. ILK promotes an aggressive lung cancer phenotype with prognostic and therapeutic value through functions that involve KRAS, IPP complex and RSU1, rendering ILK a promising biomarker and therapeutic target in lung adenocarcinoma.


Comparison of MRI with radiography for detecting structural lesions of the sacroiliac joint using CT as standard of reference: results from the SIMACT study.
Radiographs of sacroiliac (SI) joints are used for the detection of structural damage in patients with axial spondyloarthritis (axSpA), but are often difficult to interpret. Here, we address the question how the T1-weighted MRI (T1w MRI) sequence compares with radiography for SI joints' structural lesions using low-dose CT as the standard of reference. Radiographs, T1w MRI and low-dose CT of the SI joints from 110 patients (mean age 36.1 (19-57) years, 52% males and 48% females; 53% with axSpA, 21 non-radiographic axSpA and 32% radiographic axSpA, 47% with non-SpA) referred to the rheumatologist because of unclear chronic back pain, but possible axSpA, were scored for structural lesions (erosions, sclerosis, joint space changes and an overall impression of positivity). Using low-dose CT as the standard of reference, T1w MRI showed markedly better sensitivity with significantly more correct imaging findings compared with radiography for erosions (79% vs 42%; p=0.002), joint space changes (75% vs 41%; p=0.002) and overall positivity (85% vs 48%; p=0.001), respectively, while there were no differences between X-rays and MRI-T1 sequence regarding specificity (>80% for all scores). Only for sclerosis, MRI-T1 was inferior to radiography (sensitivity 30% vs 70%, respectively), however, not statistically significant (p=0.663). T1w MRI was superior to radiography in the detection of structural lesion of the SI joints in patients with axSpA. Future studies should focus on finding an agreement on the definition of MRI-T1 positivity.


The continuing spread of West Nile virus in the western hemisphere.
West Nile virus (WNV) has historically been considered to be among the least virulent of the Japanese serogroup viruses of the family Flaviviridae, genus Flavivirus. However, recent epidemics associated with severe and fatal neuroinvasive disease have changed that perception. The emergence of a virus subtype with greater epidemic potential and virulence in the early 1990s facilitated the geographic expansion and westward spread of WNV; in 1999, it first appeared in the western hemisphere. Because of the broad host and vector range, the virus has become established in much of the region, and there is little chance that it will be eliminated. Transmission is difficult to predict and even more difficult to prevent and control. The cost-effectiveness of human WNV vaccines is uncertain. The building of laboratory diagnostic, epidemiologic, and vector-control capacity in WNV-enzootic countries is critical to the development of effective prevention and control strategies for WNV infection, as well as for other potential emerging vectorborne viral diseases.


Transduction of Escherichia coli by bacteriophage P1 in soil.
Transduction of Escherichia coli W3110(R702) and J53(RP4) (10(4) to 10(5) CFU/g of soil) by lysates of temperature-sensitive specialized transducing derivatives of bacteriophage P1 (10(4) to 10(5) PFU/g of soil) (P1 Cm cts, containing the resistance gene for chloramphenicol, or P1 Cm cts::Tn501, containing the resistance genes for chloramphenicol and mercury [Hg]) occurred in soil amended with montmorillonite or kaolinite and adjusted to a -33-kPa water tension. In nonsterile soil, survival of introduced E. coli and the numbers of E. coli transductants resistant to chloramphenicol or Hg were independent of the clay amendment. The numbers of added E. coli increased more when bacteria were added in Luria broth amended with Ca and Mg (LCB) than when they were added in saline, and E. coli transductants were approximately 1 order of magnitude higher in LCB; however, the same proportion of E. coli was transduced with both types of inoculum. In sterile soil, total and transduced E. coli and P1 increased by 3 to 4 logs, which was followed by a plateau when they were inoculated in LCB and a gradual decrease when they were inoculated in saline. Transduction appeared to occur primarily in the first few days after addition of P1 to soil. The transfer of Hg or chloramphenicol resistance from lysogenic to nonlysogenic E. coli by phage P1 occurred in both sterile and nonsterile soils. On the basis of heat-induced lysis and phenotype, as well as hybridization with a DNA probe in some studies, the transductants appeared to be the E. coli that was added. Transduction of indigenous soil bacteria was not unequivocally demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)


Low child survival index in a multi-dimensionally poor Amerindian population in Venezuela.
Warao Amerindians, who inhabit the Orinoco Delta, are the second largest indigenous group in Venezuela. High Warao general mortality rates were mentioned in a limited study 21 years ago. However, there have been no comprehensive studies addressing child survival across the entire population. To determine the Child Survival-Index (CSI) (ratio: still-living children/total-live births) in the Warao population, the principal causes of childhood death and the socio-demographic factors associated with childhood deaths. We conducted a cross-sectional epidemiological survey of 688 women from 97 communities in 7 different subregions of the Orinoco Delta. Data collected included socio-demographic characteristics and the reproductive history of each woman surveyed. The multidimensional poverty index (MPI) was used to classify the households as deprived across the three dimensions of the Human Development Index. Multivariable linear regression and Generalized Linear Model Procedures were used to identify socioeconomic and environmental characteristics statistically associated with the CSI. The average CSI was 73.8% ±26. The two most common causes of death were gastroenteritis/diarrhea (63%) and acute respiratory tract Infection/pneumonia (18%). Deaths in children under five years accounted for 97.3% of childhood deaths, with 54% occurring in the neonatal period or first year of life. Most of the women (95.5%) were classified as multidimensionally poor. The general MPI in the sample was 0.56. CSI was negatively correlated with MPI, maternal age, residence in a traditional dwelling and profession of the head of household other than nurse or teacher. The Warao have a low CSI which is correlated with MPI and maternal age. Infectious diseases are responsible for 85% of childhood deaths. The low socioeconomic development, lack of infrastructure and geographic and cultural isolation suggest that an integrated approach is urgently needed to improve the child survival and overall health of the Warao Amerindians.


Principles of Hippocratic Medicine from the Perspective of Modern Medicine.
In this paper authors described some of the principles and theses of Hippocratic medicine. They emphasized that regardless existing controversial opinions as to whether Hippocrates stated some theses or not, and controversial views on some of his principles, he is often called the "father" of medicine, who laid the foundations in medicine as a science. Hippocrates gave recommendations on the doctor's behavior towards the patient, which is relevant up today. His holistic approach to medicine is becoming more and more relevant in the modern medicine. The application of the Hippocratic Oath today depends on the legislation of individual states, related to how legal solutions in some states are pro or contra to it. Authors opened and discussed his attitudes that mental illnesses are a sign of a diseased brain, his consideration the food as medicine and that the disease came from the intestines. Also issue of prognosis of the disease was opened and discussed as well as and Hippocrates's consideration of work and physical activity as the most appropriate medicine. Furthermore, authors considered importance of Hippocratic medicine related to Creative psychopharmacotherapy based on therapeutic communication and the creative satisfaction of needs in the therapeutic relationship with patients and in the recovery itself. Finally, an example of creatively use of the principle of Hippocratic medicine: "work as the most appropriate medicine" in therapeutic communication with patients through an ecological approach called "Ecopsychiatry", under the slogan presented in the media to the general public: "Cleansing nature improves your mental health" was described.


Wells Score and Poor Outcomes Among Adult Patients With Subsegmental Pulmonary Embolism: A Cohort Study.
Since the introduction of computed tomography pulmonary angiography, isolated subsegmental pulmonary embolism has become a commonly recognized clinical problem, but its clinical relevance remains unclear. The objective of the present study was to evaluate the extent to which the simplified Wells score discriminates between patients with varying levels of risk of complications after presenting with subsegmental pulmonary embolism. Retrospective cohort study. Patients included had subsegmental pulmonary embolism (1 or multiple emboli limited to subsegmental arteries). Primary explanatory variable was the simplified Wells score, categorized as high (>4) or low (≤4). The primary outcome was time to death or new venous thromboembolism. Kaplan-Meier techniques and Cox regression analysis were used to compare the survival experience of patients with high versus low Wells score with and without adjustment for active malignancy, age, Charlson score, previous venous thromboembolism, and previous major surgery in the last 30 days. Seventy-nine patients with subsegmental pulmonary embolism were included. Patients with a high Wells score had a 4-fold increased risk of the composite outcome (hazard ratio = 4.2, 95% confidence interval [CI] = 2.0-8.9, P < .001). Other covariates significantly associated with increased risk in univariate analyses included active malignancy, a low serum albumin, and an increased Charlson score. In multivariate Cox regression analyses adjusting for these other factors, a high Wells score remained significant (hazard ratio 5.5, 95% CI 2.4-12.6, P < .001). High Wells score is associated with death or new venous thromboembolism during follow-up among patients with subsegmental pulmonary embolism. ClinicalTrials.gov number, NCT01372514.


[Own experience in surgical treatment of the pineal region and midbrain tumors via the infratentorial approach].
Nine cases of tumours located in the pineal and midbrain region in adults operated on between November 1998 and July 2002 in Dept. of Neurosurgery, Central Military Hospital in Warsaw are reported. The patients (2 men and 7 women) were aged from 27 and 69 years (mean age 43.6 years). Their main initial symptoms were caused by hydrocephalus. The histopathological examination revealed anaplastic pinealoma in 2 cases, and pineocytoma, pineal cyst, mesencephalic glial cyst, protoplasmatic astrocytoma, epidermoid cyst, unclear glial scar, and papillary ependymoma in single cases. Five patients had been treated, usually elsewhere, with shunt implantation prior to the surgery. Occipito-suboccipital osteoplastic craniotomy was performed in each case and tumours were totally removed microsurgically via the infratentorial epicerebellar approach. In one case a part of the glial periaqueductal tumour was resected additionally via the fourth ventricle and aqueduct in one stage. Postoperative haematomas in the third and fourth ventricle were found in 2 cases. Main complaints after the surgery included transient diplopia. All the patients improved significantly and resumed their previous life activities. Follow-up ranged from 3 to 44 months. Three patients with pineal tumours and one with a small postoperative ependymoma recurrence were irradiated after the surgery. One patient had been irradiated prior to surgery. Very good results of the surgical treatment of tumours in this area suggest that such patients should be referred earlier to one stage surgical management, as the procedure is easier to perform and shunt implantation may be avoided.


Libelloidini, new name for an old tribe (Neuroptera Ascalaphidae).
Almost a half century ago, Tjeder (1972) stated that the genus Ascalaphus had been interpreted in a sense other than that defined by its type species (see Pantaleoni and Loru 2018). So, the generic name Ascalaphus Fabricius, 1775, became the senior synonym of Helicomitus McLachlan, 1871, and the genus Libelloides, Schäffer, 1763, was reserved for the Palearctic diurnal coloured owlflies, which until then were considered to belong to the genus Ascalaphus. Even though Tjeder's proposition produced a dramatic change in a long-term "prevailing usage", it was immediately and universally accepted as necessary. However, surprisingly, this change was never followed by the consequent necessary nomenclatural changes at the family-group name level.


[Primary malignant lymphoma of the prostate: report of a case achieving complete response to combination chemotherapy and review of 22 Japanese cases].
A 70-year-old man presented with complaints of difficult urination, perineal pain and lassitude. An enlarged, hard and nodular prostate was palpable on digital rectal examination. Needle biopsy of the prostate was performed, which revealed diffuse large B-cell non-Hodgkin's lymphoma by immunohistochemical studies. Right internal and external iliac nodes were swollen on computed tomographic scan (CT) of the pelvis. No abnormal finding was seen on abdominal CT, upper gastrointestinal fiberscopy and bone marrow histology. Therefore, the disease was classified into the clinical stage II according to Ann Arbor's criteria. The patient achieved complete response (CR) to five cycles of combination chemotherapy, CHOP, and survives more than two years without recurrence. Primary malignant lymphoma of the prostate is a rare prostatic malignancy. Only 22 Japanese cases with primary prostatic lymphoma have been reported to our knowledge. In 23 cases including ours the majority of the patients were older than 60 years, and their histopathology was mostly diffuse lymphoma, which belongs to intermediate grade of non-Hodjkin's lymphoma according to the Working Formulation's Classification. Nineteen out of 23 cases (83%) were divided into localized stage i.e. stage I or II. In these reports, three of five cases treated with either radical prostatectomy or radiotherapy alone resulted in death or progressive disease. On the other hand, 11 out of 16 cases (69%) who received chemotherapy alone or with other therapy obtained CR. Primary lymphoma of prostate has previously been considered to have a poor prognosis. Our results, however, suggest that patients with this malignancy respond well to combined chemotherapy, and could possibly be cured when the disease is confined to the localized stage.