Neuroprotection during cardiac surgery: strategies to reduce cognitive decline.
Although the population receiving cardiac surgery is older and therefore more prone to cognitive deterioration, these difficulties have declined over the last ten years. It is likely that the multiple changes introduced to cardiac surgery over time have had a cumulative benefit in protecting the brain. The most likely causes of cognitive difficulties are microemboli delivered to the brain during surgery, altered cerebral perfusion and an inflammatory response. The interventions that have been implemented can be divided into those which have attempted to reduce the potential causes of damage and those aimed at reducing the impact by attempting to protect the brain. The evidence for three main types of intervention (equipment, techniques and drugs) is reviewed in this paper. Although many interventions are available only a few have shown a clear benefit. Progress in the future will require larger studies to address this multifactorial problem.


Isolation, X location and activity of the marsupial homologue of SLC16A2, an XIST-flanking gene in eutherian mammals.
X chromosome inactivation (XCI) achieves dosage compensation between males and females for most X-linked genes in eutherian mammals. It is a whole-chromosome effect under the control of the XIST locus, although some genes escape inactivation. Marsupial XCI differs from the eutherian process, implying fundamental changes in the XCI mechanism during the evolution of the two lineages. There is no direct evidence for the existence of a marsupial XIST homologue. XCI has been studied for only a handful of genes in any marsupial, and none in the model kangaroo Macropus eugenii (the tammar wallaby). We have therefore studied the sequence, location and activity of a gene SLC16A2 (solute carrier, family 16, class A, member 2) that flanks XIST on the human and mouse X chromosomes. A BAC clone containing the marsupial SLC16A2 was mapped to the end of the long arm of the tammar X chromosome and used in RNA FISH experiments to determine whether one or both loci are transcribed in female cells. In male and female cells, only a single signal was found, indicating that the marsupial SLC16A2 gene is silenced on the inactivated X.


Molecular cloning of pheR in Escherichia coli K-12.
The regulator gene pheR, which in Escherichia coli controls the expression of pheA, the structural gene for chorismate mutase P-prephenate dehydratase, was cloned on to multicopy plasmids directly from the E. coli chromosome; this was achieved with the aid of the tetracycline resistance transposon, Tn10, that had been inserted very close to the pheR gene. Subsequently, pheR was subcloned on a 1.1-kilobase-pair fragment on the plasmid vector pBR322; its position on the plasmid was localized by the method of gamma delta-mediated transpositional inactivation. The pheR gene product was identified in maxicells and found to be a protein of subunit molecular weight 19,000, suggesting that the coding segment of the gene is about 500 nucleotide pairs long.


[Transmissing electron microscopy of the vitreo-macular border in clinically significant diabetic macular edema].
The authors examined samples of the epimacular tissue in clinically significant macular edema by means of the transmissing electron microscopy. They did not found morphological differences between samples from patients already treated by means of laser photocoagulation before the pars plana vitrectomy and those without the laser treatment. Findings may be divided into three groups: (1) the inner limiting membrane (ILM) covered with collagen vitreous fibers, (2) cells' elements of the fibroblasts category, and (3) fibrous astrocytes in the vitreous cortex constituting one- or multilayer cellular membranes.


Gastrojejunal disconnection in the presence of purulent peritonitis as an alternative approach in gastroduodenal operations.
A two stage operation is presented, for example, a life-saving procedure that halts further leakage and drainage of abscess by a modification of the gastrojejunal disconnection and reconstruction. It may be considered as an alternative approach in gastroduodenal operations in the presence of purulent peritonitis, especially in delayed surgical treatment.


Is Extra Virgin Olive Oil the Critical Ingredient Driving the Health Benefits of a Mediterranean Diet? A Narrative Review.
Most chronic diseases are preventable with a healthy diet, although there is debate about the optimal dietary approach. Increasingly more countries are focusing on food-based guidelines rather than the traditional nutrient-based approach. Although there is good agreement on plant foods, controversy remains about the types and amounts of fats and oils. This narrative review aims to systematically summarize and evaluate the latest evidence on the protective effects of extra virgin olive oil (EVOO) on disease risk factors. A systematic search of the relevant literature using PubMed, Cochrane Library, and Embase databases was conducted for the years 2000 through December 2022. A narrative synthesis was then undertaken. Of 281 retrieved articles, 34 articles fulfilled our inclusion criteria and were included. Compared with other dietary fats and low-fat diets, EVOO is superior in the management of clinical biomarkers including lowering blood pressure and LDL-c, increasing protective HDL-c, improving glycemic control, and weight management. The protective effects of EVOO are likely due to its polyphenol content rather than the monounsaturated fat content. It is therefore important to promote the regular use of EVOO in the context of healthy dietary patterns such as the Mediterranean diet for maximal health benefit.


Duloxetine: a new pharmacologic therapy for stress urinary incontinence.
The dual serotonin (5-HT)/norepinephrine (NE) reuptake inhibitor duloxetine shows promise as a pharmacologic therapy for stress urinary incontinence. This agent modulates lower urinary tract function through selective inhibition of 5-HT and NE receptor sites. It works centrally at Onuf's nucleus to increase activity of the pudendal nerve. Duloxetine facilitates sphincter activity during urine storage but not during voiding, maintaining the bladder-sphincter synergy. Because it inhibits both 5-HT and NE reuptake, duloxetine appears to offer an advantage over agents that inhibit reuptake of a single neurotransmitter.


APOE Locus-Associated Mitochondrial Function and Its Implication in Alzheimer's Disease and Aging.
The Apolipoprotein E (APOE) locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either upregulated or downregulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.


Comparison of different collection systems for sorted household waste in Sweden.
Composition and quantity per person of municipal solid waste (MSW) have been analyzed in six municipalities in southern Sweden with similar socio-economic conditions but with different collection systems. Samples of residual waste have been sorted, classified and weighed in 21 categories during 26 analyses that took place from 1998-2004. Collection data of the total waste flow, including source sorted recycling materials, in the same area have been compiled and compared. Multivariate data analyses have been applied. Weight-based billing reduced delivered amounts of residual household waste by 50%, but it is unknown to what extent improper material paths had developed. With curbside collection more metal, plastic and paper packaging was separated and left to recycling. When separate collection of biodegradables was included in the curbside system, the overall sorting of dry recyclables increased. The large uncertainty associated with waste composition analyses makes it difficult to draw strong conclusions regarding the effects on specific recyclables or the changes in the composition of the residual waste.


Theoretical detection threshold of the proton-acoustic range verification technique.
Range verification in proton therapy using the proton-acoustic signal induced in the Bragg peak was investigated for typical clinical scenarios. The signal generation and detection processes were simulated in order to determine the signal-to-noise limits. An analytical model was used to calculate the dose distribution and local pressure rise (per proton) for beams of different energy (100 and 160 MeV) and spot widths (1, 5, and 10 mm) in a water phantom. In this method, the acoustic waves propagating from the Bragg peak were generated by the general 3D pressure wave equation implemented using a finite element method. Various beam pulse widths (0.1-10 μs) were simulated by convolving the acoustic waves with Gaussian kernels. A realistic PZT ultrasound transducer (5 cm diameter) was simulated with a Butterworth bandpass filter with consideration of random noise based on a model of thermal noise in the transducer. The signal-to-noise ratio on a per-proton basis was calculated, determining the minimum number of protons required to generate a detectable pulse. The maximum spatial resolution of the proton-acoustic imaging modality was also estimated from the signal spectrum. The calculated noise in the transducer was 12-28 mPa, depending on the transducer central frequency (70-380 kHz). The minimum number of protons detectable by the technique was on the order of 3-30 × 10(6) per pulse, with 30-800 mGy dose per pulse at the Bragg peak. Wider pulses produced signal with lower acoustic frequencies, with 10 μs pulses producing signals with frequency less than 100 kHz. The proton-acoustic process was simulated using a realistic model and the minimal detection limit was established for proton-acoustic range validation. These limits correspond to a best case scenario with a single large detector with no losses and detector thermal noise as the sensitivity limiting factor. Our study indicated practical proton-acoustic range verification may be feasible with approximately 5 × 10(6) protons/pulse and beam current.


Efficient preparation and characterization of silver-polyphenylsilane nanocomposites.
Silver-polyphenylsilane nanocomposites have been effectively prepared by the dehydrocoupling reaction of phenylsilane (PS, PhSiH3) to polyphenylsilane (PPS, [PhSiH]n) in the presence of silver nitrate. The one-step reduction of Ag(+1) nitrate to stable Ag(0) nanoparticles is mediated by PS, resulting in the formation of Ag-PPS composites. The Ag-PPS nanocomposites were characterized by various analytical techniques such as XRD, TEM, FE-SEM, and solid-state UV-vis. TEM and FE-SEM data clearly show that the silver nanoparticles with the size of < 20 nm are well dispersed throughout the PPS matrix in the nanocomposites. XRD patterns are consistent with those for fcc crystalline silver. The size of silver nanoparticles increased with increasing the relative molar concentration of silver salts added. It was found that in the absence of PS, most of the silver nanoparticles undergo macroscopic precipitation by aggregation, indicating that PPS is essential to stabilize the silver nanoparticles by the complexation of Si-H to the silver metal centers.


Effects of 2 G hypergravity exposure on Bobwhite (Colinus virginianus) and Japanese quail (Coturnix coturnix japonica).
We compared reproductive fitness and early postnatal growth of Bobwhite (Colinus virginianus) and Japanese (Coturnix coturnix japonica) quail incubated and hatched during 2 G centrifugation. Fertilized Bobwhite and Japanese quail eggs were placed in portable incubators on the 8-ft International Space Station Test Bed (ISSTB) Centrifuge at NASA Ames Research Center. The quail eggs were incubated throughout hatching and reared until Postnatal day (P)4 at either 1.0, 1.2 or 2.0 G. Two days before hatching, candling revealed significantly greater numbers of viable Bobwhite than Japanese quail eggs at all g-loads. Bobwhite quail exhibited significantly better hatching success at all g-loads than did Japanese quail. Bobwhite hatchlings were sensitive to gravitational loading as evidenced by reduced postnatal body mass and length of 2 G hatchlings relative to 1 G control hatchlings. In contrast, mass and length of Japanese quail hatchlings were unaffected by 1.2 or 2 G exposure. Together, our findings provide evidence for superior viability and hatching success in Bobwhite quail relative to Japanese quail, coupled with greater sensitivity of postnatal body growth and development to 2 G loading. Bobwhite quail may be better suited than Japanese quail for scientific studies on space biology platforms.


[Clinical and experimental studies on vitronectin in bacterial pneumonia].
The pathophysiologic significance of vitronectin in bacterial pneumonia was studied. The following conclusions were obtained. 1) Plasma vitronectin in healthy persons was 252.3 +/- 65.2 micrograms/ml. The level was markedly decreased to 167.0 +/- 42.7 micrograms/ml in patients with bacterial pneumonia. However, it was gradually increased to the normal levels as recovering with pneumonic lesions. It was also found the negative correlation between plasma vitronectin and CRP (r = -0.7) and plasma fibrinogen (r = -0.6) in the course of pneumonia. 2) Vitronectin was localized on elastic fibers of the basement membrane of bronchial epithelium, the alveolar interstitium and the blood vessels in normal lung tissue by immunohistochemical method. On the other hand, vitronectin was significantly localized on inflammatory sites, in particular, fibrin matrix and fibrous sites in pneumonic lesions. These findings were more dominant in severe pneumonia. The results are suggested that reducing in plasma vitronectin appears to be depended on the vitronectin consumption in pneumonic site. 3) In in vitro experiments, activating PMNs, alveolar macrophages and pulmonary fibroblasts were easy to adhered to vitronectin. This adhesiveness to vitronectin was also observed in the strains of S. pneumoniae, S. aureus, and P. aeruginosa, but not in K. pneumoniae and E. coli. These results suggest that vitronectin plays an important role for host defense mechanism by mediating to cell-bacteria interaction and it promotes the recover of injured tissue by induction with pulmonary fibroblasts.


Antibodies to the nef protein and to nef peptides in HIV-1-infected seronegative individuals.
The silent period that follows infection by the human immunodeficiency virus (HIV-1) and precedes seroconversion remains a problem for the screening of blood supply, and knowledge about the mechanism involved in the maintenance of latency is only fragmentary. Using purified nef recombinant protein and six synthetic nef peptides, antibodies to the product of an HIV-1 regulatory gene, the negative regulatory factor (nef) involved in maintenance of proviral latency, were detected by Western blot and radioimmunoassay techniques in HIV-1-seronegative, viral antigen-negative, and virus culture-negative individuals at risk for HIV infection. This antibody response to nef was correlated in eight individuals with the detection of HIV-1 proviral DNA by oligonucleotide hybridization, following enzymatic amplification of HIV DNA in peripheral blood mononuclear cells. Such latent HIV infections have now been followed for up to 6 or 10 months in five individuals. In addition, retrospective and prospective analysis of HIV-1-seropositive individuals have shown (1) antibodies to nef preceding seroconversion, and (2) the persistence of antibodies to nef and of HIV-1 proviral DNA in a case of spontaneous complete HIV-1 seronegativation. Since DNA amplification cannot be currently considered for routine use, screening for anti-nef antibodies followed by confirmation by DNA amplification could represent a basis for new diagnostic strategies. Beyond their diagnostic implications, these findings, suggesting that regulatory genes of the HIV-1 provirus can be expressed prior to the initiation of virion synthesis, may also be applicable in the design of alternative vaccines against the acquired immunodeficiency syndrome.


The value of computed tomography in the assessment of suspected ruptured abdominal aortic aneurysm.
The objective of this study was to determine the diagnostic value of computed tomography (CT) in patients with suspected ruptured abdominal aortic aneurysm. The study was an interrogation of a prospectively gathered computerized database. The study was performed at a regional vascular surgery unit. Six hundred fifty-two consecutive patients were admitted to this unit with suspected ruptured abdominal aortic aneurysm between January 1, 1989, and December 31, 1996. Seventy-four patients (11.3%) in whom the diagnosis was in doubt on clinical grounds alone underwent urgent CT. A total of 47 men and 27 women with a median age of 73 years (range, 52 to 86 years) were evaluated. CT and operative findings were compared. CT correctly diagnosed rupture in 22 of 28 patients who underwent operation and correctly excluded rupture in 30 of 39 patients who underwent operation. The sensitivity and specificity of CT when compared with operative findings were therefore 79% and 77%, respectively. These data indicate that CT has little additional diagnostic value. If in the opinion of an experienced vascular surgeon rupture cannot be excluded on clinical grounds alone, and the patient has no medical contraindications to abdominal aortic aneurysm repair, then the patient should be taken directly to the operating department.


[New treatment of peritoneal carcinomatosis from colorectal cancer. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy].
Peritoneal carcinomatosis (PC) is commonly seen in colorectal cancer and is uniformly fatal. Cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIIC) is a new treatment in strictly selected patients with PC. CS includes peritonectomy procedures and resection of infiltrated viscera leaving no macroscopic tumor thicker than 2.5 mm behind. Peritoneal perfusion with mitomycin C at a temperature of 40 degrees -41 degrees C is performed at the end of surgery. The postoperative morbidity and mortality rates are 20%-30% and 4%-8% respectively. Median survival is 1-2 years and the 5-year survival is 19%.


Alterations in Lipid Profile of the Aging Kidney Identified by MALDI Imaging Mass Spectrometry.
During aging, the kidney undergoes functional and physiological changes that are closely affiliated with chronic kidney disease (CKD). There is increasing evidence supporting the role of lipid or lipid-derived mediators in the pathogenesis of CKD and other aging-related diseases. To understand the role of lipids in various metabolic processes during kidney aging, we conducted matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) analysis in kidneys harvested from young (2 months old, n = 3) and old mice (24 months old, n = 3). MALDI-IMS analysis showed an increase in ceramide level and a decrease in sphingomyelin (SM) and phosphatidylcholine (PC) levels in kidneys of old mice. The increased expression of cPLA2 and SMPD1 protein in aged kidney was confirmed by immunohistochemistry and Western blot analysis. Our MALDI-IMS data showed the altered distribution of lipids in aged kidney as indicative of aging-related functional changes of the kidney. Combined analysis of MALDI-IMS and IHC confirmed lipidomic changes and expression levels of responsible enzymes as well as morphological changes.


Artifacts reduction in strain maps of tagged magnetic resonance imaging using harmonic phase.
Tagged Magnetic Resonance Imaging (MRI) is a noninvasive technique for examining myocardial function and deformation. Tagged MRI can also be used in quasi-static MR elastography to acquire strain maps of other biological soft tissues. Harmonic phase (HARP) provides automatic and rapid analysis of tagged MR images for the quantification and visualization of myocardial strain. We propose a new artifact reduction method in strain maps. Image intensity of the DC component is estimated and subtracted from spatial modulation of magnetization (SPAMM) tagged MR images. DC peak interference in harmonic phase extraction is greatly reduced after DC component subtraction. The proposed method is validated using both simulated and MR acquired tagged images. Strain maps are obtained with better accuracy and smoothness after DC component subtraction.


The learning curve measured by operating times for laparoscopic and open gastric bypass: roles of surgeon's experience, institutional experience, body mass index and fellowship training.
Surgeons must overcome a substantial learning curve before mastering laparoscopic Roux-en-Y gastric bypass (LRYGBP). This learning curve can be defined in terms of mortality, morbidity or length of surgery. The aim of this study was to compare the learning curves in terms of surgical time for the first 3 surgeons performing LRYGBP in our hospital with the length of surgery for open gastric bypass (CONTROLS). We compared 494 primary LRYGBPs performed by 3 surgeons (393 by 1st SURGEON, 57 by 2nd SURGEON and 44 by 3rd SURGEON) to 159 open vertical banded gastroplasty-Roux-en-Y gastric bypasses (CONTROLS). Data for LRYGBP patients were prospectively obtained. Factors that significantly affected the length of surgery were identified by univariate and multivariate linear regression analysis. LRYGBP and CONTROL patients were similar in age, height, weight and BMI, although more CONTROLS were male. Median time for the 1st SURGEON performing LRYGBP dropped for each subsequent 100 operations: 1st 100 - 190 min, 2nd 100 - 135 min, 3rd 100 - 110 min and 4th 100 - 100 min. Median time for 2nd SURGEON performing LRYGBP was 120 min, 3rd SURGEON 173 min and CONTROLS 64 min. Length of surgery significantly correlated with surgical experience in terms of numbers of operations and BMI of patient. Times for 2nd SURGEON, a fellowship trained laparoscopic surgeon, started significantly faster than 1st SURGEON's, but did not significantly improve with experience. 3rd SURGEON's initial times were similar to 1st SURGEON's, but his times improved more rapidly with experience. Times for CONTROLS were significantly faster than all laparoscopic groups and did not correlate with operation number or patient BMI. The length of surgery for LRYGBPs continued to shorten beyond 400 operations for the first surgeon performing LRYGBP in our hospital. Previous fellowship training in LRYGBP shortened surgical times during initial clinical experience as an attending for the second surgeon. The learning curve was truncated because of the already established LRYGBP program.


Exceptional flexibility in the sequence requirements for coronavirus small envelope protein function.
The small envelope protein (E) plays a role of central importance in the assembly of coronaviruses. This was initially established by studies demonstrating that cellular expression of only E protein and the membrane protein (M) was necessary and sufficient for the generation and release of virus-like particles. To investigate the role of E protein in the whole virus, we previously generated E gene mutants of mouse hepatitis virus (MHV) that were defective in viral growth and produced aberrantly assembled virions. Surprisingly, however, we were also able to isolate a viable MHV mutant (DeltaE) in which the entire E gene, as well as the nonessential upstream genes 4 and 5a, were deleted. We have now constructed an E knockout mutant that confirms that the highly defective phenotype of the DeltaE mutant is due to loss of the E gene. Additionally, we have created substitution mutants in which the MHV E gene was replaced by heterologous E genes from viruses spanning all three groups of the coronavirus family. Group 2 and 3 E proteins were readily exchangeable for that of MHV. However, the E protein of a group 1 coronavirus, transmissible gastroenteritis virus, became functional in MHV only after acquisition of particular mutations. Our results show that proteins encompassing a remarkably diverse range of primary amino acid sequences can provide E protein function in MHV. These findings suggest that E protein facilitates viral assembly in a manner that does not require E protein to make sequence-specific contacts with M protein.


Principal component analysis modeling of Head-and-Neck anatomy using daily Cone Beam-CT images.
To model Head-and-Neck anatomy from daily Cone Beam-CT (CBCT) images over the course of fractionated radiotherapy using principal component analysis (PCA). Eighteen oropharyngeal Head-and-Neck cancer patients, treated with volumetric modulated arc therapy (VMAT), were included in this retrospective study. Normal organs, including the parotid and submandibular glands, mandible, pharyngeal constrictor muscles (PCMs), and spinal cord were contoured using daily CBCT image datasets. PCA models for each organ were developed for individual patients (IP) and the entire patient cohort/population (PP). The first 10 principal components (PCs) were extracted for all models. Analysis included cumulative and individual PCs for each organ and patient, as well as the aggregate organ/patient population; comparisons were made using the root-mean-square (RMS) of the percentage predicted spatial displacement for each PC. Overall, spatial displacement prediction was achieved at the 95% confidence level (CL) for the first three to four PCs for all organs, based on IP models. For PP models, the first four PCs predicted spatial displacement at the 80%-89% CL. Differences in percentage predicted spatial displacement between mean IP models for each organ ranged from 2.8% ± 1.8% (1st PC) to 0.6% ± 0.4% (4th PC). Differences in percentage predicted spatial displacement between IP models vs the mean IP model for each organ based on the 1st PC were <12.9% ± 6.9% for all organs. Differences in percentage predicted spatial displacement between IP and PP models based on all organs and patients for the 1st and 2nd PC were <11.7% ± 2.2%. Tissue changes during fractionated radiotherapy observed on daily CBCT in patients with Head-and-Neck cancers, were modeled using PCA. In general, spatial displacement for organs-at-risk was predicted for the first 4 principal components at the 95% confidence levels (CL), for individual patient (IP) models, and at the 80%-89% CL for population-based patient (PP) models. The IP and PP models were most predictive of changes in glandular organs and pharyngeal constrictor muscles, respectively.


Covert video surveillance continues to provoke debate.
When the editor invites comment on a response to an analysis of a criticism of a protocol already defended by the author in this journal, the issue is clearly contentious. I will comment briefly on Thomas's paper in this issue of the journal, and look at points of agreement as well as dissent.


Interaction of chelating agents with cadmium in mice and rats.
The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl2 and on the whole body retention and tissue distribution of cadmium after the IV application of 115mCdCl2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatment of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination of the retention and distribution of Cd in mice, it was demonstrated that the combined application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of 115mCd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes.


Exposure to multiple environmental agents and their effect.
All children are exposed to multiple physical, chemical and biological challenges that can result in adverse health effects before and after birth. In this context, the danger of multiple exposures cannot be assessed from a single-chemical approach as used in classical toxicology. To open up a 'negotiation space' for the problem of multiple exposure to environmental stressors, defined as any physical, chemical or biological entity that can induce an adverse response. In this context, two further questions obtain: to what extent can synergistic risks be assessed, and how far could potential adverse effects be prevented by enhanced regulation? A discussion of two general approaches is taken: 1) the investigation of mixtures such as smoking or air pollution without specifying the individual agents, and 2) the investigation of individual substances with a focus on possible interactions in the context of dose to receptor. Although mixtures of compounds can have effects, it may not be possible to ascribe causation to a single compound. Furthermore, cumulative low-dose insult can, in some circumstances, be more toxic than a single high-dose exposure, e.g. endocrine disruptive effects of a combination of PCBs and dioxins which disrupt the thyroid hormone status; this tends to contradict elements of classical toxicology, . These cumulative insults may further combine with heavy metals and can disrupt the heme synthesis. It is possible that groups of pollutants could be used to test their cumulative capacity to multiple stress-susceptible receptor targets as is done in smoking and air pollution. This methodology could be used for further groups of potential pollutants, for example those associated with cleaning products, or cosmetics. Testing individual substances with a focus on interactions means that not only chemicals but also concurrent diseases should be taken into account. We suggest that the enhanced regulation of potential multiple stressors falls into two discrete categories. The first comprises a more precautionary approach (as demonstrated by the banning of chemicals such as some brominated flame retardants in Europe). The second comprises a more 'permissive' liberal approach involving the initial study of an individual compound, and subsequent interrogation of that compound in combination with another (as demonstrated by lowering the carcinogenicity of aflatoxin by vaccination against hepatitis B). It is necessary to define and study groups of multiple stressors as in US EPA's Framework for Cumulative Risk Assessment (U.S. EPA 2003). Recent increased knowledge of the greater sensitivity of the unborn baby, the infant and the child, has led to general recognition that a higher degree of precaution is now needed in regulating for multiple stressors on the young. The more liberal permissive approach proceeding from established effects of the individual exposures is becoming less acceptable now that we know that there is much we do not understand about chronic effects of stressors during the early development phases. Conflicts over which approach to take may have to be resolved through engagement and negotiation with a wide community of stakeholders. This "community of interest" may include fundamental research scientists, practicing clinical paediatricians, patient groups, and others concerned with the health and wellbeing of infants and children.


Antigen-specific. I region-restricted interactions in vitro between tumor cell lines and T cell hybridomas.
A series of H-2d B cell tumor lines and one monocytic tumor cell line were shown to be capable of I region-restricted antigen presentation to I-A-d- and I-Ed- restricted, antigen-specific cloned T cell hybridomas. For the most part, antigen presentation correlated with the present of Ia antigens on the presenting cells, although in a few interesting cases Ia-expression lines failed to present antigen. These T cell hybridomas, together with the B cell and to monocyte tumor cell lines, offer a unique set of tools to study the phenomenon of I region-restricted antigen presentation.


Green fluorescent protein reporter system with transcriptional sequence heterogeneity for monitoring the interferon response.
The interferon (IFN) response is initiated by a variety of triggers, including viruses and foreign RNA, and involves several receptors and intracellular mediators. Although there are common cis-acting consensus sequences in the promoters of many genes stimulated during the IFN response, they exhibit core and context heterogeneity that may lead to differential transcriptional activity. We have developed and validated a live cell-based enhanced green fluorescent protein (EGFP) reporter system employing more than a hundred constructs containing multiple viruses and IFN response elements derived from a variety of promoters involved in immunity to viruses. Common and distinct response patterns were observed due to promoter heterogeneity in response to different stimuli, including IFN-α, TLR3-agonist double-stranded RNA, and several viruses. This information should serve as a resource in selecting specific reporters for sensing nonself ligands.


Pharmacotherapy of 'treatment resistant' type 2 diabetes.
Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice. Areas covered: This article proposes a definition for 'treatment resistant diabetes', analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies. Expert opinion: Before considering intensifying the pharmacotherapy of a patient with poorly controlled T2D, it is important to verify treatment adherence, target obesity and consider various non pharmacological improvement quality interventions. If treatment resistant diabetes is defined as not achieving glycated haemoglobin target despite oral triple therapy with a third glucose-lowering agent added to metformin-sulfonylurea dual treatment, the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor and a sodium glucose cotransporter type 2 (SGLT2) inhibitor may offer new opportunities before considering injectable therapies. Insulin basal therapy (± metformin) may be optimized by the addition of a SGLT2 inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist.


Transplantation of an autologous mesothelial cell sheet prepared from tunica vaginalis prevents post-operative adhesions in a canine model.
Post-operative adhesions often cause severe complications such as bowel obstruction and abdominopelvic pain. Previously, we reported that transplantation of a mesothelial cell sheet is effective for preventing adhesion in rat model. We also proposed a new technique for harvesting autologous mesothelial cells from tunica vaginalis without intra-abdominal maneuvers. In this study, we examined whether an autologous mesothelial cell sheet can prevent post-operative peritoneal adhesions in a canine adhesion model. Mesothelial cells were isolated from the tunica vaginalis of male beagles. Isolated cells were cultured on fibrin gel. We named this construct the "mesothelial cell sheet." Animals underwent surgery to induce peritoneal adhesion formation and were then transplanted with the mesothelial cell sheets (sheet group, n = 4), fibrin gel (fibrin group, n = 4), or no materials (sham group, n = 4). Four weeks after the transplantation, we evaluated adhesion formation and scored adhesion levels. The abdominal wall transplanted with the mesothelial cell sheet was covered with mesothelium. The total adhesion score of the sheet group was significantly lower than that of the fibrin group and the sham group. These results indicated that transplantation of an autologous mesothelial cell sheet is effective for preventing post-operative adhesion formation in the canine adhesion model. Our mesothelial cell sheet has the potential to be a powerful adhesion prophylactic material in surgery.


Genetically engineered bananas resistant to Xanthomonas wilt disease and nematodes.
Banana is an important staple food crop feeding more than 100 million Africans, but is subject to severe productivity constraints due to a range of pests and diseases. Banana Xanthomonas wilt caused by Xanthomonas campestris pv. musacearum is capable of entirely destroying a plantation while nematodes can cause losses up to 50% and increase susceptibility to other pests and diseases. Development of improved varieties of banana is fundamental in order to tackle these challenges. However, the sterile nature of the crop and the lack of resistance in Musa germplasm make improvement by traditional breeding techniques either impossible or extremely slow. Recent developments using genetic engineering have begun to address these problems. Transgenic banana expressing sweet pepper Hrap and Pflp genes have demonstrated complete resistance against X. campestris pv. musacearum in the field. Transgenic plantains expressing a cysteine proteinase inhibitors and/or synthetic peptide showed enhanced resistance to a mixed species population of nematodes in the field. Here, we review the genetic engineering technologies which have potential to improve agriculture and food security in Africa.


[Prevalence of dyslipidemia in outpatients of the Spanish health service: the HISPALIPID Study].
We intended to estimate the prevalence of dyslipidemia among patients attending outpatient clinics of the Spanish health service. HISPALIPID is a multicenter, cross-sectional study performed in 33,913 patients (55.7% women) with a mean age of 54.6 +/- 18.3 years attended in outpatient clinics across 15 of the 17 autonomous communities of Spain. 1,461 physicians (78.8% primary care physicians, and 21.2% specialists) participated in the study. Patients were considered having dyslipidemia if their doctor had established a previous diagnosis. A total of 8,256 patients (52.4% women, mean age 62.4 +/- 12.4 years) had been diagnosed with dyslipidemia, representing a global prevalence of 24.3% (CI95%: 23.8-24.8) (M: 26.2%; W:22.9%; P<0.001). The communities with the higher and lower prevalence were the Canary Islands (33.9%) and Cantabria (18.6%), respectively. About 87% dyslipemic patients presented an additional cardiovascular risk factor and 36.7% of dyslipemic patients had an associated cardiovascular disease. The prevalence of dyslipidemia is high in patients attending outpatient clinics of the Spanish health service (one out of four patients). In addition, these patients are at a high cardiovascular risk.


Triterpenes and meroterpenes from Ganoderma lucidum with inhibitory activity against HMGs reductase, aldose reductase and α-glucosidase.
Seven new compounds including four lanostane triterpenoids, lucidenic acids Q-S (1-3) and methyl ganoderate P (4), and three triterpene-farnesyl hydroquinone conjugates, ganolucinins A-C (5-7), one new natural product ganomycin J (8), and 73 known compounds (9-81) were isolated from fruiting bodies of Ganoderma lucidum. The structures of the compounds 1-8 were determined by spectroscopic methods. Bioactivities of compounds isolated were assayed against HMG-CoA reductase, aldose reductase, α-glucosidase, and PTP1B. Ganolucidic acid η (39), ganoderenic acid K (44), ganomycin J (8), and ganomycin B (61) showed strong inhibitory activity against HMG-CoA reductase with IC50 of 29.8, 16.5, 30.3 and 14.3μM, respectively. Lucidumol A (67) had relatively good effect against aldose reductase with IC50 of 19.1μM. Farnesyl hydroquinones ganomycin J (8), ganomycin B (61), ganomycin I (62), and triterpene-farnesyl hydroquinone conjugates ganoleuconin M (76) and ganoleuconin O (79) possessed good inhibitory activity against α-glucosidase with IC50 in the range of 7.8 to 21.5μM. This work provides chemical and biological evidence for the usage of extracts of G. lucidum as herbal medicine and food supplements for the control of hyperglycemic and hyperlipidemic symptoms.


[Biomonitoring for occupational medicine].
Biomonitoring is an essential occupational-medical instrument for assessing the exposure of chemical agents of workers. It is an integral part of preventive medical examinations as far as established analytical procedures and values for evaluating biomonitoring results are available. The DFG Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has published values for evaluating biomonitoring results. Those values are health related values such as the Biological Tolerance Value (BAT) and descriptive values such as the "Biologischer Arbeitsstoff-Referenzwert" (BAR) and Exposure Equivalents for Cancerous Substances (EKA), respectively. Moreover the combination of acceptance values and tolerance values derived by the Committee on Hazardous Substances (AGS) from exposure-risk-relations with the EKA allow the deduction of risk-related values too. The European Biological Limit Value (BLV) and the Biological Guidance Value are also important in the countries of the European Union. The results of a biological monitoring represent person-related data and therefore are subject to the rules on professional confidentiality that apply to physicians.


Active and passive touch: the influence of exploration time on form recognition.
In a study of the effect of self-produced movement on tactual form recognition 30 male and 30 female college students actively or passively touched cooky -cutter forms with the preferred index finger to identify the shapes. In a static passive condition, the forms were pressed on the fingers. Ss were limited to either 5 or 30 sec of stimulus exposure time. Results indicate that active touch was superior to either passive static or passive sequential touch. Adding stimulus change failed to improve performance. Recognition accuracy was greater with 30 sec of exposure, but 5 sec of active touch produced accuracy equivalent to that produced by longer periods of passive stimulation.


Object-independent wavefront sensing method based on an unsupervised learning model for overcoming aberrations in optical systems.
This Letter introduces the idea of unsupervised learning into object-independent wavefront sensing for the first time, to the best of our knowledge, which can achieve fast phase recovery of arbitrary objects without labels. First, a fine feature extraction method which only depends on the wavefront aberrations is proposed. Then, a lightweight neural network and an optical feature system are combined to form an unsupervised learning model, and the neural network is promoted to be well trained by reversely outputting fine features. Simulation results prove that the proposed method can effectively overcome the aberrations (static or variable) existing in the optical system and achieve wavefront sensing of different objects with high precision and efficiency.


Intestinal microRNAs and bacterial taxa in juvenile mice are associated, modifiable by allochthonous lactobacilli, and affect postnatal maturation.
The interplay between the intestinal microbiota and host is critical to intestinal ontogeny and homeostasis. MicroRNAs (miRNAs) may be an underlying link. Intestinal miRNAs are microbiota-dependent and, when shed in the lumen, affect resident microorganisms. Yet, longitudinal relationships between intestinal tissue miRNAs, luminal miRNAs, and luminal microorganisms have not been elucidated, especially in early life. Here, we investigated the postnatal cecal miRNA and microbiota populations, their relationship, and their impact on intestinal maturation in specific pathogen-free mice; we also assessed if they can be modified by intervention with allochthonous probiotic lactobacilli. We report that cecal and cecal content miRNA and microbiota signatures are temporally regulated, correlated, and modifiable by probiotics with implications for intestinal maturation. These findings help understand causal relationships within the gut ecosystem and provide a basis for preventing and managing their alterations in diseases throughout life. IMPORTANCE The gut microbiota affects intestinal microRNA (miRNA) signatures and is modified by host-derived luminal miRNA. This suggests the existence of close miRNA-microbiota relationships that are critical to intestinal homeostasis. However, an integrative analysis of these relationships and their evolution during intestinal postnatal maturation is lacking. We provide a system-level longitudinal analysis of miRNA-microbiota networks in the intestine of mice at the weaning transition, including tissue and luminal miRNA and luminal microbiota. To address causality and move toward translational applications, we used allochthonous probiotic lactobacilli to modify these longitudinal relationships and showed that they are critical for intestinal maturation in early life. These findings contribute to understand mechanisms that underlie the maturation of the intestinal ecosystem and suggest that interventions aiming at maintaining, or restoring, homeostasis cannot prescind from considering relationships among its components.


Changes in the vestibulo-ocular reflex: a study of elderly day hospital patients.
The vestibulo-ocular reflex (VOR) of 50 elderly day hospital patients (mean age of 82 years) was studied with the head autorotation test. Amplitude gain, phase and the highest frequency band reached were determined in the five frequency bands of 1, 2, 3, 4, and 5 Hz. Of the 50 patients, 81% had abnormal results. The gain of the elderly was significantly increased to 1.06-1.24 in the frequency bands of 3, 4, and 5 Hz in comparison with that of a control group. The elderly showed constantly a phase lead of 8-19 degrees in the frequency range of 1-4 hz and in this range differed significantly from the control group. The percentage of the elderly who reached high frequencies of head movements was reduced to 55% in the frequency band of 3 Hz and to 30% in the frequency band of 4 Hz. These findings may lead to oscillopsia and explain the high prevalence of dizziness and falls among the elderly.


Rural and urban problem drinkers in six Southern states.
In 1994-1997 we conducted a four-wave longitudinal study of rural and urban problem drinkers in six Southern United States states to examine rural/urban differences in predictors of service use and course of drinking. This report describes early rural/urban differences from a brief interview with over 3,000 community individuals and among 525 identified problem drinkers. Overall, we found rural/urban differences in alcohol consumption at the community level but only demographic differences among problem drinkers. Our newly developed screening interview for alcohol disorders had excellent agreement (kappa = 0.72) for lifetime disorders and good agreement (kappa = 0.53) for recent disorders against structured diagnostic interviews for DSM-IV criteria.


Evidence of Ebola Virus Replication and High Concentration in Semen of a Patient During Recovery.
In one patient over time, we found that concentration of Ebola virus RNA in semen during recovery is remarkably higher than blood at peak illness. Virus in semen is replication-competent with no change in viral genome over time. Presence of sense RNA suggests replication in cells present in semen.


Contact photoallergy to isothipendyl chlorhydrate.
Isothipendyl chlorhydrate is an azaphenothiazine, an active ingredient of an antipruriginous gel, Apaisyl gel® (Merck Médication Familiale, Dijon, France). Although Apaisyl gel is registered and used worldwide, we present the first case of contact photoallergy to isothipendyl chlorhydrate to our knowledge. The diagnosis suspected on the basis of a positive UVA photopatch test to chlorpromazine was confirmed by a strongly positive UVA Apaisyl gel photopatch test and our photophysical studies. This case confirms the need to keep the phenothiazines in the photopatch test standard series as a diagnostic marker of phenothiazine photoallergy.


Serum allantoin and aminothiols as biomarkers of chronic heart failure.
Background Oxidative stress (OS) represents the primary mediator of chronic heart failure (CHF) development and progression. It is well established that homocysteine is able to generate reactive oxygen species. Small amounts of allantoin in human serum result from free radical action on urate and may provide a stable marker for in vivo free radical activity. To investigate whether some easily measurable indexes such as antioxidants (uric acid, glutathione) and related molecules (allantoin, homocysteine and cysteine) can serve as OS biomarkers. Methods We investigated 75 stable CHF patients. Aminothiols and purine compound levels were determined by capillary electrophoresis. Results The homocysteine level was markedly elevated in CHF patients, whatever the aetiology. Parameters of the transsulfuration pathway and the investigated purine compounds were significantly increased. Conversely, total glutathione was decreased. The allantoin/uric acid ratio was significantly higher in CHF patients with an hyperhomocysteinaemia >17 μmol/L. All parameters of the transsulfuration and purine degadation pathways were significantly correlated, suggesting an OS in CHF patients. Conclusion Our data show an imbalance of serum aminothiols and purine compounds in these CHF patients on adapted therapy. We suggest that the evaluation and control of these new markers may help improve the OS that participates in the progression of the disease.


ePharmaLib: A Versatile Library of e-Pharmacophores to Address Small-Molecule (Poly-)Pharmacology.
Bioactive compounds oftentimes bind to several target proteins, thereby exhibiting polypharmacology. Experimentally determining these interactions is however laborious, and structure-based virtual screening (SBVS) of bioactive compounds could expedite drug discovery by prioritizing hits for experimental validation. Here, we present ePharmaLib, a library of 15,148 e-pharmacophores modeled from solved structures of pharmaceutically relevant protein-ligand complexes of the screening Protein Data Bank (sc-PDB). ePharmaLib can be used for target fishing of phenotypic hits, side effect predictions, drug repurposing, and scaffold hopping. In retrospective SBVS, a good balance was obtained between computational efficiency and predictive accuracy. As a proof of concept, we carried out prospective SBVS in conjunction with a photometric assay, which inferred that the mechanism of action of neopterin (an endogenous immunomodulator) putatively stems from its inhibition (IC50 = 18 μM) of the human purine nucleoside phosphorylase. This ready-to-use library is freely available at http://www.pharmbioinf.uni-freiburg.de/epharmalib.


Sex- and Age-Specific Optimal Anthropometric Indices as Screening Tools for Metabolic Syndrome in Chinese Adults.
To compare the predictive ability of six anthropometric indices for identification of metabolic syndrome (MetS) and to determine their optimal cut-off points among Chinese adults. A total of 59,029 participants were enrolled. Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and conicity index (CI) were measured. Receiver-operating characteristic curves analyses were performed to determine the discriminatory power of these indices for the identification of cardiometabolic risks and diagnosis of MetS. The differences in the area under the curve (AUC) values among the indices were evaluated. The Youden index was used to determine the optimal cut-off points. WHtR and BRI exhibited the highest AUC values for identifying MetS and most cardiometabolic risk factors in both sexes, whereas ABSI showed the lowest AUC value. The general optimal cut-off points in women were 23.03 kg/m2 for BMI, 77.25 cm for WC, 0.490 for WHtR, and 3.179 for BRI; those in men were 24.64 kg/m2 for BMI, 87.25 cm for WC, 0.510 for WHtR, and 3.547 for BRI. The AUC values and cut-off points of the indices were also analyzed in each age and BMI category. In Chinese adults, WHtR and BRI showed a superior predictive power for MetS in both sexes, which can be used as simple and effective screening tools for cardiometabolic risks and MetS in clinical practice.


Coupling of excitation to Ca2+ release is modulated by dysferlin.
Dysferlin, the protein missing in limb girdle muscular dystrophy 2B and Miyoshi myopathy, concentrates in transverse tubules of skeletal muscle, where it stabilizes voltage-induced Ca2+ transients against loss after osmotic shock injury (OSI). Local expression of dysferlin in dysferlin-null myofibres increases transient amplitude to control levels and protects them from loss after OSI. Inhibitors of ryanodine receptors (RyR1) and L-type Ca2+ channels protect voltage-induced Ca2+ transients from loss; thus both proteins play a role in injury in dysferlin's absence. Effects of Ca2+ -free medium and S107, which inhibits SR Ca2+ leak, suggest the SR as the primary source of Ca2+ responsible for the loss of the Ca2+ transient upon injury. Ca2+ waves were induced by OSI and suppressed by exogenous dysferlin. We conclude that dysferlin prevents injury-induced SR Ca2+ leak. Dysferlin concentrates in the transverse tubules of skeletal muscle and stabilizes Ca2+ transients when muscle fibres are subjected to osmotic shock injury (OSI). We show here that voltage-induced Ca2+ transients elicited in dysferlin-null A/J myofibres were smaller than control A/WySnJ fibres. Regional expression of Venus-dysferlin chimeras in A/J fibres restored the full amplitude of the Ca2+ transients and protected against OSI. We also show that drugs that target ryanodine receptors (RyR1: dantrolene, tetracaine, S107) and L-type Ca2+ channels (LTCCs: nifedipine, verapamil, diltiazem) prevented the decrease in Ca2+ transients in A/J fibres following OSI. Diltiazem specifically increased transients by ∼20% in uninjured A/J fibres, restoring them to control values. The fact that both RyR1s and LTCCs were involved in OSI-induced damage suggests that damage is mediated by increased Ca2+ leak from the sarcoplasmic reticulum (SR) through the RyR1. Congruent with this, injured A/J fibres produced Ca2+ sparks and Ca2+ waves. S107 (a stabilizer of RyR1-FK506 binding protein coupling that reduces Ca2+ leak) or local expression of Venus-dysferlin prevented OSI-induced Ca2+ waves. Our data suggest that dysferlin modulates SR Ca2+ release in skeletal muscle, and that in its absence OSI causes increased RyR1-mediated Ca2+ leak from the SR into the cytoplasm.


Hepatitis B virus and hepatitis D virus infection in women with or at risk for HIV infection in the United States.
Hepatitis D virus (HDV) requires co-infection with hepatitis B virus (HBV). Human immunodeficiency virus (HIV) shares transmission routes with these viruses. Among 4,932 US women infected with or at-risk for HIV during 1994-2015, HBV surface antigen (HBsAg) positivity was more common in women with HIV (2.8% vs. 1.2%; p = 0.001); HDV was more common among participants enrolled during 2013-2015 (p = 0.0004) and those with resolved rather than active hepatitis C (1.9% vs. 0.5%; p = 0.02). Among HBsAg-positive women (n = 117), HDV antibody prevalence was 22% and did not vary by HIV status; HDV infection was associated with the presence of advanced fibrosis/cirrhosis at enrollment (adjusted odds ratio, 5.70; 95% confidence interval, 1.46-22.29). Our results demonstrate the importance of HDV testing in HBV-infected US women.


Interaction of tumor cells and immune system in the metastatic process.
The metastatic process is rather complicated and relatively inefficient. Millions of tumor cells are constantly shedding from the primary tumor into the blood stream, but very few of them are able to form metastatic tumors in the different organs or tissues of the host. It is widely accepted that metastatic cells have to possess a complex array of various properties that allow them to complete the metastatic cascade. The realization of the metastatic potential largely depends on the ability of tumor cells to evade host defense mechanisms. The potential role of specific and nonspecific immune mechanisms in the control of metastatic spread and growth is the subject of the present review. A better understanding of the mechanisms of antimetastatic defense is of prime importance for development of efficient immunotherapeutic methods for the treatment and eradication of disseminated tumor metastases.


Tumor suppressor Fhit protein interacts with protoporphyrin IX in vitro and enhances the response of HeLa cells to photodynamic therapy.
Fhit, the product of tumor suppressor fragile histidine triad (FHIT) gene, exhibits antitumor activity of still largely unknown cellular background. However, it is believed that Fhit-Ap(3)A or Fhit-AMP complex might act as a second class messenger in cellular signal transduction pathway involved in cell proliferation and apoptosis. We demonstrate here for the first time that the photosensitizer, protoporphyrin IX (which is a natural precursor of heme) binds to Fhit protein and its mutants in the active site in vitro. Furthermore, PpIX inhibits the enzymatic activity of Fhit. Simultaneously, PpIX shows lower binding capacity to mutant Fhit-H96N of highly reduced hydrolase activity. In cell-based assay PpIX induced HeLa cell death in Fhit and Fhit-H96N-dependent manner which was measured by means of MTT assay. Moreover, HeLa cells stably expressing Fhit or mutant Fhit-H96N were more susceptible to protoporphyrin IX-mediated photodynamic therapy (2J/cm(2)) than parental cells.


The development of a new agent for the treatment of inflammatory/allergic conditions.
The search for new drugs for the treatment of reversible obstructive airways disease has been a major pursuit of the pharmaceutical industry for almost two decades. Little progress has been achieved. The acceptance that asthma is a multi-facetted disease state has led to the development of a new complex in vivo screen in the macaque monkey. This model is mediated through mast cells which stain positively with alcian blue/safranin. A new therapeutic agent, nedocromil sodium, was significantly more active than sodium cromoglycate in this primate model of airway disease. Extensive clinical trials have shown that this new agent is effective in the treatment of the reversible component of obstructive airways disease.


Some aspects of abdominal surgery in the elderly patient.
Most operations on elderly patients are of an urgent nature. If time permits, measures to improve cardiac, respiratory and renal functions in the appropriate ways should be undertaken. During recovery from anesthesia careful but adequate sedation will reduce the risk of myocardial ischemia. Throughout the postoperative period constant encouragement of the older patient is particularly helpful.Transverse abdominal incisions and the frequent use of temporary gastrostomy are advocated.External hernia, hiatus hernia, peptic ulcer, carcinoma of the stomach, biliary disease, appendicits, intestinal obstruction, and carcinoma of the large intestine are discussed specifically, with special reference to the practical details of management in the elderly patient.


Rescued Chondrogenesis of Mesenchymal Stem Cells under Interleukin 1 Challenge by Foamyviral Interleukin 1 Receptor Antagonist Gene Transfer.
Background: Mesenchymal stem cells (MSCs) and their chondrogenic differentiation have been extensively investigated in vitro as MSCs provide an attractive source besides chondrocytes for cartilage repair therapies. Here we established prototype foamyviral vectors (FVV) that are derived from apathogenic parent viruses and are characterized by a broad host range and a favorable integration pattern into the cellular genome. As the inflammatory cytokine interleukin 1 beta (IL1β) is frequently present in diseased joints, the protective effects of FVV expressing the human interleukin 1 receptor antagonist protein (IL1RA) were studied in an established in vitro model (aggregate culture system) of chondrogenesis in the presence of IL1β. Materials and Methods: We generated different recombinant FVVs encoding enhanced green fluorescent protein (EGFP) or IL1RA and examined their transduction efficiencies and transgene expression profiles using different cell lines and human primary MSCs derived from bone marrow-aspirates. Transgene expression was evaluated by fluorescence microscopy (EGFP), flow cytometry (EGFP), and ELISA (IL1RA). For evaluation of the functionality of the IL1RA transgene to block the inhibitory effects of IL1β on chondrogenesis of primary MSCs and an immortalized MSC cell line (TERT4 cells), the cells were maintained following transduction as aggregate cultures in standard chondrogenic media in the presence or absence of IL1β. After 3 weeks of culture, pellets were harvested and analyzed by histology and immunohistochemistry for chondrogenic phenotypes. Results: The different FVV efficiently transduced cell lines as well as primary MSCs, thereby reaching high transgene expression levels in 6-well plates with levels of around 100 ng/ml IL1RA. MSC aggregate cultures which were maintained in chondrogenic media without IL1β supplementation revealed a chondrogenic phenotype by means of strong positive staining for collagen type II and matrix proteoglycan (Alcian blue). Addition of IL1β was inhibitory to chondrogenesis in untreated control pellets. In contrast, foamyviral mediated IL1RA expression rescued the chondrogenesis in pellets cultured in the presence of IL1β. Transduced MSC pellets reached thereby very high IL1RA transgene expression levels with a peak of 1087 ng/ml after day 7, followed by a decrease to 194 ng/ml after day 21, while IL1RA concentrations of controls were permanently below 200 pg/ml. Conclusion: Our results indicate that FVV are capable of efficient gene transfer to MSCs, while reaching IL1RA transgene expression levels, that were able to efficiently block the impacts of IL1β in vitro. FVV merit further investigation as a means to study the potential as a gene transfer tool for MSC based therapies for cartilage repair.


Genetic Factors Associated with Morphine Consumption in Women Undergoing Laparoscopic Cholecystectomy: A Prospective Cohort Study.
Morphine has been a crucial analgesic agent used perioperatively in various surgical procedures. Genetic factors can lead to morphine dose requirement interpatient variability. Our objective was to determine the contribution of genetic polymorphisms in human μ-opioid receptor gene (OPRM1), ATP binding cassette gene (ABCB1) and rs2952768 to the variation of the perioperative morphine consumption in women undergoing laparoscopic cholecystectomy. This is a prospective cohort study that included 102 adult Arab females undergoing laparoscopic cholecystectomy. The exposures were carrying the genetic variants of OPRM1, ABCB1 and rs2952768. Our primary outcome was total morphine or morphine equivalent dose required perioperatively. The secondary outcomes were pain score during the first 24 hours and adverse drug reactions. A standardized, general anaesthesia was used for all subjects. In addition to the genetic factors, we also investigated non-genetic factors influencing post-operative pain sensitivity and morphine consumption. Both (rs1799971, A>G) in OPRM1 and (rs2952768, T>C) showed statistically significant association with intra-operative total morphine dose requirements. Patients carrying the "G" allele in OPRM1 had a significantly higher total morphine mean rank dose compared to the AA genotype [62.9 vs 47.1, p=0.008]. Furthermore, patients homozygous for the rs2952768 (T>C) minor allele "CC" had a higher mean rank compared to the other genotypes [72.7 vs 50.1, p=0.046]. OPRM1 (rs1799971) and rs2952768 are associated with variation of intra-operative morphine consumption in laparoscopic cholecystectomy. This study was registered at ClinicalTrials.gov, NCT04621864. https://clinicaltrials.gov/ct2/show/NCT04621864.


In-house preparation and evaluation of (125)I-histamine progesterone tracer for radioimmunoassay of progesterone.
The progesterone tracer for the development of in-house radioimmunoassay was prepared in two steps clearly described. First, activation of 11α-hemisuccinate progesterone (progesterone-11 α HS) and labeling of histamine with (125)I, and second, conjugation of activated 11α-HS progesterone with iodinated histamine. The purification of the tracer was carried out by gel filtration on Sephadex G-25. The radiochemical purity of purified the tracer was 95%. The maximum binding using solid phase (coated tubes) reached 41% and the non specific binding didn't exceed 5%. The tracer stored at different temperatures 10°C and -6°C was stable during 12 weeks. The skim milk provided assay better sensitivity (0.22 ng/mL) than serum (0.28 ng/mL).


[Whooping cough: biological diagnosis].
Whooping cough is a respiratory infection particularly severe for infants. The agents of the disease are the bacteria Bordetella pertussis and B. parapertussis. Before vaccination, the disease affected majority of the children. Due to the high circulation of the bacteria, adolescents and adults were regularly in contact with the bacteria and had natural boosters. Forty years after generalized vaccination in some countries, a change in the transmission of the disease is observed. Children between 2 and 5-10 years of age are not infected (depending of the vaccine used and the vaccine calendar) because they were vaccinated in their infancy. However, adolescents and adults are becoming susceptible because they do not receive any vaccinal or natural boosters. They can be infected and contaminated infants are too young to be vaccinated. Clinical symptoms in adolescents and adults, previously vaccinated or infected, are very variable and for this reason biological diagnosis are now necessary to confirm the infection. These diagnostics are culture, PCR and serology.


Body Function and Structure, Activity, and Participation Limitations of Lung Transplant Recipients Within the Scope of the International Classification of Functioning, Disability, and Health.
There is no study in the literature that specifically evaluates lung transplant recipients in the long-term under the framework of the International Classification of Functioning, Disability, and Health. The aim of this study was to evaluate the relationships between lung transplant recipient age, age at transplant, and comorbidity levels and the body structure and functions and the activity and participation levels of patients within the scope of the International Classification of Functioning, Disability, and Health. We evaluated 27 lung transplant recipients according to the International Classification of Functioning, Disability, and Health items in domain b (body functions), domain s (body structures), and domain d (activities and participation). For domain b, sleep functions, psychosocial status, respiratory functions, and upper and lower extremity exercise capacity were evaluated. Posture was evaluated for the s domain. Balance, arm functional capacity, health-related quality of life, and physical activity were evaluated for domain d. As the age of lung transplant recipients and the age at transplant increase, their sleep quality and respiratory functions decreased, and postural impairment increased. There was a negative correlation between age at transplant and functional exercise capacity (P < .05). As the comorbidity level of the recipient increases, the upper and lower extremity exercise capacity, physical activity level, and quality of life declined. There was a moderately positive correlation between the level of comorbidity and balance disorder (P < .05). We found the International Classification of Functioning, Disability, and Health framework to be useful for the evaluation and for planning pulmonary rehabilitation for lung transplant recipients; it can bring a new perspective to physiotherapists specialized in cardiopulmonary rehabilitation.


Electrospun chitosan-coated fibers of poly(L-lactide) and poly(L-lactide)/poly(ethylene glycol): preparation and characterization.
Fibrous poly(L-lactide) (PLLA) and bicomponent PLLA/poly(ethylene glycol) mats were prepared by electrospinning and then were coated with chitosan. The presence of chitosan coating was proved by scanning electron microscopy and by fluorescence microscopy. On contact with blood, the chitosan coating led to changes in erythrocyte shape and in their aggregation. The haemostatic activity of the mats increased with increasing chitosan content. Microbiological studies against Staphylococcus aureus revealed that the chitosan coating imparts antibacterial activity to the hybrid mats. The combined haemostatic and antibacterial activities render these novel materials suitable for wound-healing applications.


Long-term return behavior of Chinese whole blood donors.
It is important to understand donor return behavior to maintain sufficient numbers of blood donors in developing countries where blood supplies are often inadequate. A total of 54,267 whole blood (WB) donors who donated between January 1 and March 31, 2008, at the five blood centers in China were followed for 2.5 years. Logistic regression was conducted to identify factors associated with their return behavior. A recurrent-event Cox proportional-hazard model was used to evaluate the overall effect of demographic variables and return behavior among first-time donors. Donors with previous donation history were more likely to return and the number of previous returns was positively associated with future return (odds ratios, 3.31, 4.82, and 8.16 for one, two to three, and more than three times compared to none). Thirty-four percent of donors (first-time donor, 21%; repeat donor, 54%) made at least one return donation, with 14% returning in the first 9 months. The multivariable logistic regression model for all WB donors and the Cox proportional hazard model for first-time donors showed consistent predictors for return: female sex, older age (≥ 25 years), larger volume (300 or 400 mL), and donating in satellite collection site. Encouraging first-time donors to make multiple donations is important for keeping adequate blood supply. The finding that first-time and repeat donors shared the same predictors for return indicates that retention strategies on repeat donors may be effective on first-time donors. Studies on motivators and barriers to return are needed, so that successful retention strategies can be tailored.


A comparison of stimulus fading and stimulus shaping on perceptual category learning.
Errorless learning strategies such as stimulus fading and stimulus shaping are commonly used to teach complex skills like categorisation and concept formation. Despite widespread use, very few studies have explored the comparative effectiveness of these procedures in well-controlled analyses. The vast majority of existing studies have been undertaken with clinical populations and have involved small numbers of participants (e.g., Single-case designs). The present study sought to compare stimulus fading, stimulus shaping, and trial-and-error learning in a perceptual categorisation task. In Experiment 1, we found robust benefits of stimulus shaping when compared to stimulus fading or trial-and-error learning on measures of initial acquisition of discrimination and one measure of stimulus generalisation. These findings were replicated in a second experiment in which the dimension of fading/shaping was changed from a modification of the comparison stimuli (S-) to a modification of the target stimulus (S +). We discuss the implications of our findings for the selection of errorless learning strategies in clinical settings.


Astrocytes as mediators of immune and inflammatory responses in the CNS.
The long-standing view that the brain is isolated from the effects of the immune system has recently been challenged, with experimental evidence suggesting that in response to invasion by microorganisms, the CNS can mount its own defense by resident cells, such as the microglia and astrocytes. Both cell types produce and secrete a number of cytokines and therefore can potentially modulate and integrate the communication between hematogenous cells and resident cells of the CNS. This manuscript will commence with a brief overview of astrocytic functions in the CNS, and proceed to discuss astrocytic responses that may regulate CNS inflammation. Specifically, it will address (1) the function of astrocytes as the antigen presenting cells (APCs) of the CNS, and (2) the role afforded by astrocyte-derived cytokines, and astrocytic responses to cytokines secreted elsewhere, in mediating and sustaining immune responses. Finally, some recent experimental evidence on the possibility that astroglial impairment by pathogens may contribute to the etiology of neurologic diseases will be highlighted.


Zn and Pb concentration in seminal plasma in reference to selected parameters of semiological assessment of bull semen.
The Zn and Pb concentration was determined in 45 samples of bull semen from three Artificial Insemination Stations (A,B,C) differing in degree of environmental pollution. Bull semen was diluted with Biociphos-Plus to such an extent as to obtain 16 million sperm cells in an insemination dose. The research aimed at assessing the correlation between zinc, lead and other parameters influencing the semiological assessment of bull semen. The content of zinc and lead was determined with the use of the flame method and an absorption spectrophotometer (AAS). Positive, statistically significant correlations between zinc concentration and semen motility were observed in station A at r = 0.61 and station C at r = 0.614. In station B these correspondences were not statistically confirmed. Positive correlation at r = 0.583 was observed in case of zinc and the ejaculate volume only in station B. No statistically significant correlation was observed between lead concentration and the analyzed parameters.


Reversible, coenzyme-A-mediated inactivation of biosynthetic condensing enzymes in yeast: a possible regulatory mechanism.
alpha-Isopropylmalate synthase [3-hydroxy-4-methyl-3-carboxyvalerate 2-oxo-3-methylbutyrate-lyase (CoA-acetylating); EC 126.96.36.199], the enzyme catalyzing the first committed step in leucine biosynthesis, and homocitrate synthase [3-hydroxy-3-carboxyadipate 2-oxoglutarate-lyase (CoA-acetylating); EC 184.108.40.206], the first enzyme in lysine biosynthesis in yeast, are rapidly inactivated in the presence of low concentrations of coenzyme A, a product of both reactions. Closely related compounds like 3-dephospho-coenzyme A or oxidized coenzyme A are almost without effect, as are other sulfhydryl compounds. Citrate (si)-synthase [citrate oxaloacetate-lyase (pro-3S-CH2-COO-minus leads to acetyl-CoA); EC 188.8.131.52] appears to be completely resistant against inactivation by coenzyme A. Inactivated alpha-isopropylmalate and homocitrate synthases can be reactivated by dialysis, but not by adding excess substrate. Protection against coenzyme-A-mediated inactivation is provided by relatively high concentrations of the alpha-ketoacid substrate or the specific end product inhibitor of each of the two enzymes. The coenzyme-A-mediated inactivation of alpha-isopropylmalate synthase has been more closely investigated. It requires the presence of divalent metal ions, with Zn++being most effective. The inactivation does not require molecular oxygen. It occurs in the presence of low concentrations of substrates and is observed in toluene-treated cells. These results, together with evidence that alpha-isopropylmalate synthase and homocitrate synthase are located in the mitochondria, suggest a mechanism by which increasing intra-mitochondrial coenzyme A concentrations might serve as a signal of decreasing acetyl-coenzyme A levels, triggering a temporary inactivation of biosynthetic acetyl-coenzyme A-consuming reactions in order to channel the available acetyl-coenzyme A into the citrate cycle.


[Etiology and therapy in anorexia nervosa (author's transl)].
ASPERGER (1963) mentioned as a very important etiological aspect of anorexia nervosa a desintegration of intellectual and thymical functions causing the fact, that these patients are not able to accept the role of an adult, especially that one of a woman. We discuss that statment in connexion with ERIKSON'S (1974) concept about "ego-identity" ("Ich-Identitat") and "negative-identity" ("negative Identitat"). The pathological family-structure seems to reinforce the situation and the existence of inadequate behavior of patients with anorexia nervosa, who are often introverted and predestinated for conditioning. The therapy of these patients should focuse on the development of ego-identity, including the treatment of the family members, the modification of the inadapted behavior and a special endocrinological therapy.


Proximal row carpectomy: an alternative to wrist fusion?
Problems with implant failure and silicone synovitis and a high complication rate in wrist arthrodesis have recently increased the interest in solutions that use residual biological articular surfaces. These include limited intercarpal fusions and proximal row carpectomy (PRC). PRC is a relatively easy procedure with few complications. We reviewed 27 personal cases. According to this study PRC offers a painless range of motion, with an average of 68 degrees flexion/extension range and an average grip strength of 60% of the contralateral side. The failure rate is 18.5%. However, failures can be successfully converted into wrist arthrodesis. Our follow-up period ranges from 6 to 36 months. Late deterioration has not been reported in the literature. On the contrary, improvement of mobility and grip strength several months after operation have been observed. We still favor PRC as a salvage procedure in order to offer the patient some motion, provided that there is no osteoarthritis over the capitate and the lunate facet preoperatively.


Phosphorescent sensor for robust quantification of copper(II) ion.
A phosphorescent sensor based on a multichromophoric iridium(III) complex was synthesized and characterized. The construct exhibits concomitant changes in its phosphorescence intensity ratio and phosphorescence lifetime in response to copper(II) ion. The sensor, which is reversible and selective, is able to quantify copper(II) ions in aqueous media, and it detects intracellular copper ratiometrically.


Replication of infectious bursal disease virus in continuous cell lines.
Three mammalian continuous cell lines--MA-104, Vero, and BGM-70--were tested for their ability to support replication of infectious bursal disease virus (IBDV). Selected tissue-culture-adapted vaccine strains and tissue-culture-adapted field isolates of IBDV replicated in the MA-104, Vero, and BGM-70 cells; cytopathic effects were most pronounced in the BGM-70 cells. The cytopathic effects of the viruses in BGM-70 cells and chicken embryo fibroblast (CEF) cultures were similar. Virus-neutralization titers of selected serum samples determined in BGM-70 cultures compared well with those obtained from CEF cultures.


[Placental chorioangiomas diagnosed during the second trimester of pregnancy: four cases].
Placental chorioangioma is a benign vascular tumor found in about 1% of pregnancies at routine histological examination of the placenta. The large placental tumor may cause serious fetal complications. We report 4 cases of placental chorioangioma diagnosed during the second trimester. Three pregnancies with rapidly growing tumors measuring more than 4 cm led to fetal hydrops and perinatal death despite thoracocentesis and cesarean delivery at 33 weeks (1 case) and repeated amniodrainage (1 case). The only surviving infant presented with a 3.3cm tumor which grew progressively to 8 cm at 38 weeks and did not induce polyhydramnios or hydrops. Although aggressive prenatal management of placental chorioangioma has been reported using amniodrainage, intrauterine transfusions, embolization, or ligation of the tumor vessel supply, prognosis remains poor for large tumors and largely depends on fetal hemodynamic tolerance.


Met and unmet needs of schizophrenia patients in a Spanish sample.
Deinstitutionalization of people with schizophrenia increases the importance of evaluating their needs. This study set out to identify the most common needs of people with schizophrenia who live in the community, analyze how those needs differ when evaluated by staff or by patients, describe the kind of help patients receive, and find out the variables that correlate with having unmet needs. A random sample of 231 outpatients with schizophrenia were evaluated with the Camberwell Assessment of Need and other predictor and outcome variables. Staff detected more needs than patients did. Mean number of needs as rated by patients was 5.36 and staff 6.6 (p < 0.001). Mean number of unmet needs was also greater when assessed by staff than by patients: 1.38 versus 1.82 (p < 0.001). The most frequently detected needs by patients involved psychotic symptoms, house upkeep, food, and information. Staff most often detected needs involving psychotic symptoms, company, daytime activities, house upkeep, food, and information. In a multiple regression model, needs were weakly associated with the clinical variables and quality of life. Needs assessment is complementary to clinical evaluation in schizophrenia.


Effect of 3-Month Aerobic Dance on Hippocampal Volume and Cognition in Elderly People With Amnestic Mild Cognitive Impairment: A Randomized Controlled Trial.
As an intermediate state between normal aging and dementia, mild cognitive impairment (MCI), especially amnestic MCI (aMCI), is a key stage in the prevention and intervention of Alzheimer's disease (AD). Whether dancing could increase the hippocampal volume of seniors with aMCI remains debatable. The aim of this study was to investigate the influence of aerobic dance on hippocampal volume and cognition after 3 months of aerobic dance in older adults with aMCI. In this randomized controlled trial, 68 elderly people with aMCI were randomized to either the aerobic dance group or the control group using a 1:1 allocation ratio. Ultimately, 62 of 68 participants completed this study, and the MRI data of 54 participants were included. A specially designed aerobic dance routine was performed by the dance group three times per week for 3 months, and all participants received monthly healthcare education after inclusion. MRI with a 3.0T MRI scanner and cognitive assessments were performed before and after intervention. High-resolution three-dimensional (3D) T1-weighted anatomical images were acquired for the analysis of hippocampal volume. A total of 35 participants (mean age: 71.51 ± 6.62 years) were randomized into the aerobic dance group and 33 participants (mean age: 69.82 ± 7.74 years) into the control group. A multiple linear regression model was used to detect the association between intervention and the difference of hippocampal volumes as well as the change of cognitive scores at baseline and after 3 months. The intervention group showed greater right hippocampal volume (β [95% CI]: 0.379 [0.117, 0.488], p = 0.002) and total hippocampal volume (β [95% CI]: 0.344 [0.082, 0.446], p = 0.005) compared to the control group. No significant association of age or gender was found with unilateral or global hippocampal volume. There was a correlation between episodic memory and intervention, as the intervention group showed a higher Wechsler Memory Scale-Revised Logical Memory (WMS-RLM) score (β [95% CI]: 0.326 [1.005, 6.773], p = 0.009). Furthermore, an increase in age may cause a decrease in the Mini-Mental State Examination (MMSE) score (β [95% CI]: -0.366 [-0.151, -0.034], p = 0.002). In conclusion, 3 months of aerobic dance could increase the right and total hippocampal volumes and improve episodic memory in elderly persons with aMCI. Clinical Trial Registration: This study was registered on the Chinese Clinical Trial Registry [www.chictr.org.cn], identifier [ChiCTR-INR-15007420].


Classical trajectory calculations of intramolecular vibrational energy redistribution. II. Phenol-water complex.
Ab initio classical trajectory calculations have been applied to the intramolecular vibrational energy redistribution process of an O-H stretching vibration for phenol cation, [phenol]+, and its hydrogen-bonded water complex, [phenol-water]+. In phenol cation, a single narrow peak in the power spectrum, obtained by Fourier transformation of the autocorrelation function of its total momentum, indicates that the initial energy given to the O-H stretching oscillator of the phenol moiety is conserved and no energy flow occurs. On the other hand, for phenol-water cation, the calculated broadened power spectrum implies that the initial energy is not conserved and the energy flow causes an energy redistribution among various vibrational modes.


Ocular and orbital cysticercosis in hogs.
The prevalence of cysticercosis in hog muscles was correlated with oculo-orbital prevalence, and histologic characteristics of changes in the parasite and hog were observed. The orbital contents, globe, and eyelids of 39 hogs affected with Cysticercus cellulosae were examined. Thirty-seven parasites were found: 35 within the orbit and two intraocular. Twenty parasites with adjacent host tissue were studied histologically. Inflammatory infiltrates ranging from diffuse lymphoplasmacytic to dense granulomas were seen in 16 cysticerci. The scolex was unaltered in all specimens.


Site of action of methyldopa in lowering the blood pressure in man.
1. Methyldopa was administered to hypertensive patients in association with two different inhibitors of dopa decarboxylase, one of which, carbidopa, scarcely penetrates the central nervous system while the other, benserazide, penetrates the central nervous system when given in high doses. 2. The evidence suggests that in man, as in animals, the predominant action of methyldopa is mediated by the formation of methyldopamine and methyl-nor-adrenaline within the brain.


Response to lactating dairy cows to abomasal infusion of amino acids.
Essential amino acids most limiting for milk production and/or secretion of milk protein were determined in five trials involving infusion of amino acids into the abomasum of lactating Holstein cows. Cows were fed corn-based rations containing 10.7 to 11.5% crude protein (dry matter basis) which exceeded standard allowances for energy. All trials were Latin-square designs with 9-day periods. The abomasal infusion of methionine had no effect on secretion of milk, milk protein, or milk fat. Lysine infusion resulted in 16% of the total response in yield of milk protein that was obtained with either the 10 essential amino acids or sodium caseinate while infusion of lysine and methionine together accounted for 43% of the total response. This suggested that lysine and methionine were first and second limiting, or co-limiting, for secretion of milk protein when rations consisting primarily of corn, corn silage, and alfalfa-grass hay were fed. The primary effect was on content of milk protein rather than milk yield. In general, amino acid infusions had no effect on feed intake, milk fat, and nonprotein nitrogen content of milk. Little change occurred in concentrations in plasma of other amino acids when lysine and methionine were infused together. When concentrations were lowered, indicating increased protein synthesis, changes were too small to be statistically significant.


Differential Associations Between Excess Body Weight and Psychiatric Disorders in Men and Women.
The current investigation is the first large-scale population-based study from France that documents the association between excess body weight and common psychiatric disorders, and examines the influence of gender on the association between excess body weight and these disorders. A recent plan has been implemented in France to treat the rising rate of those who are overweight or obese, and we seek to demonstrate whether integrated treatment of excess weight and psychiatric conditions appears as indicated. Data were drawn from a cross-sectional general population survey of 17,237 adults. Past-year psychiatric disorders were assessed using the Composite International Diagnostic Interview-Short Form. Body mass index was used to determine excess weight status. Overall, 3.7% of the sample were underweight, 57% were normal weight, 28% were overweight (35% of men, 22% of women), and 11% were obese (11% of men, 11% of women). Being overweight was more common in men than women, although obesity did not differ by gender. Sociodemographic variables significantly associated with weight status included, age, marital status, education, employment status, income level, and population density. Adjusting for these variables, being overweight was associated with major depression and other disorders among women and inversely associated with drug abuse and dependence among men. Obesity was associated with major depression, panic disorder, agoraphobia, social phobia, specific phobia, and obsessive-compulsive disorder among women. Only generalized anxiety was associated with obesity among men. Past year, mental disorders were more likely associated with being overweight or obese among women as compared with men. The prevalence of these co-occurring psychiatric disorders in the context of the rising rate of obesity in France indicates a clear need for psychiatric assessment and treatment in caring for those with excess weight, especially women. Preliminary reports suggest this need is unmet within the otherwise progressive move in France to assist those struggling with excess weight.


Ultrasound and MRI for the long-term evaluation of surgical repair of the rotator cuffs.
About 1 year after surgery to repair the rotator cuff, a total of 20 patients (80% monotendinous injuries, 20% bitendinous injuries) were submitted to ultrasound and MRI to evaluate repair, quality of residual tissue, and to reveal any discrepancies between the two instrumental tests. The results showed that there was normal tendinous integrity in 16 cases (group A), while there were partial injuries, without evidence of complete lesion, in 4 cases (group B); tendinous thinning was evident in 10 patients (50%), while there were areas of intratendinous degeneration in 40% of the cases. The authors observed agreement between the data obtained by the two methods in 75% of cases, and emphasize the effectiveness of the two methods in postoperative evaluation of the cuff; they also confirm the tendinous dishomogeneousness observed in the patients in group B, not associated with poor clinical results, considering the absence of significant differences in the functional results between the two groups.


Synonymous codon usage in different protein secondary structural classes of human genes: implication for increased non-randomness of GC3 rich genes towards protein stability.
The relationship between the synonymous codon usage and different protein secondary structural classes were investigated using 401 Homo sapiens proteins extracted from Protein Data Bank (PDB). A simple Chi-square test was used to assess the significance of deviation of the observed and expected frequencies of 59 codons at the level of individual synonymous families in the four different protein secondary structural classes. It was observed that synonymous codon families show non-randomness in codon usage in four different secondary structural classes. However,when the genes were classified according to their GC3 levels there was an increase in non-randomness in high GC3 group of genes. The non-randomness in codon usage was further tested among the same protein secondary structures belonging to four different protein folding classes of high GC3 group of genes. The results show that in each of the protein secondary structural unit there exist some synonymous family that shows class specific codon-usage pattern. Moreover, there is an increased non-random behaviour of synonymous codons in sheet structure of all secondary structural classes in high GC3 group of genes. Biological implications of these results have been discussed.


[Fundamental biological model for trials of wound ballistics].
The aim of our experiment was the testing of effects of common ammunition on usable and slightly accessible biological tissue thereby to create fundamental simple biological model for trials of wounded ballistic. Like objective tissue was elected biological material - pork and beef hind-limbs, pork head, pork bodily cavity. It was discovered that objective tissue is able to react to singles types of shots in all spectrum results namely simple smooth penetration wound as well as splintery fracture in dependence on kind of using ammunition. Pork hind-limb was evaluated like the most suitable biological material for given object.


The combined transverse upper gracilis and profunda artery perforator (TUGPAP) flap for breast reconstruction.
Surgical options for breast reconstruction include alloplastic and autogenous reconstructions. In autologous cases where the abdomen is not a suitable primary donor site, secondary donor sites such as the thigh or buttock are considered. The aim of this report is to describe a novel approach, the combined transverse upper gracilis and profunda artery perforator (TUGPAP) flap, aimed at medium to large volume breast reconstruction, with a single donor site used per breast. Between January 2011 and June 2013, 32 consecutive unilateral immediate breast reconstruction cases were performed using free flaps. In nine cases, patients had previously undergone abdominal surgery, therefore abdominal flaps were excluded and TUGPAP flaps were performed. The TUGPAP flap consisted of the combination of two well-described flaps: the transverse upper gracilis (TUG) and the profunda artery perforator (PAP) flap. All TUGPAP flaps were based on two pedicles: the ascending branch of the medial circumflex femoral artery (MCFA) for the TUG component, and the profunda artery perforator itself for the PAP component. The mean size of the harvested skin paddle was 28.6 × 8 cm2 (range, 27 × 7 cm2 to 30 × 9 cm2). The average length of the TUG flap pedicle was 7 cm (range, 6-8 cm) and the PAP flap pedicle was 9 cm (range, 8.5-10 cm). The flap survival rate was 100% with no re-exploration, and no partial flap loss. Post-operatively there was one case of persistent donor site seroma, which was managed conservatively. With appropriate patient selection and surgical technique the TUGPAP flap could be a valuable option as an alternative method for autologous breast reconstruction. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015.


MicroRNAs: Roles in Regulating Neuroinflammation.
MicroRNAs (miRNAs) are small noncoding RNAs that broadly affect cellular and physiological function in all multicellular organisms. Here, the role of miRNAs in neuroinflammation is considered. miRNAs are 21- to 23-oligonucleotide RNAs that regulate translation of specific RNAs by binding to complementary regulatory RNA sequences, thereby causing mRNA degradation or sequestration. More than 5000 miRNAs likely exist in humans, and each miRNA binds an average of 200 RNAs. Specific immunomodulatory miRNAs can regulate a set of RNAs in a coordinated manner, suggesting that effective miRNA-based therapeutic manipulations for neuroinflammatory conditions may be revealed. For instance, miRNAs that preferentially inhibit translation of many cellular anti-inflammatory proteins could drive a pro-inflammatory response. Key pro-inflammatory ( miR-155, miR-27b, miR-326), anti-inflammatory ( miR-124, miR-146a, miR-21, miR-223), and mixed immunomodulatory ( let-7 family) miRNAs regulate neuroinflammation in various pathologies, including spinal cord injury, multiple sclerosis, ischemic stroke, and Alzheimer's disease. miRNAs represent a newly revealed layer of physiological complexity, the therapeutic benefits of which remain to be fully explored and exploited. In this review, we discuss the role of miRNAs in neuroinflammatory regulation and discuss how controlling miRNAs could alter cellular machinery to improve neuroinflammatory dynamics.